Professional Documents
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PHARMAOEUTICAL,
OHEMISTRY
CONTAINING THEORY AND PRACTICE OF
QUANTITATIVE ANALYSIS APPLIED
TO PHARMACY
BY
AND
SECOND EDITION
1937
INC.
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.28,1j"~' ~ir
.. , No.
Jil
,:
QUANTITATIVE PHARMACEUTICAL
CHEMISTRY
McGRAW-HILL PUBLICATIONS IN
PHARMACY
A
C. W. JOHNSON, Chairman,
Dean, University of Washington, College of Pharmacy.
EDWARD SPEASE, Acting Chairman and Consulting Ed7.'tOT,
Dean, Western Reserve University, School of Pharmaoy.
JOHN
G.
BEARD,
H. C. CHRISTENSEN,
Secretary National Assooiated Boards of Pharmacy,
Chicago, Illinois.
ZADA M. COOPER,
A.
DYE,
R.
JOHNSON,
R.
LEIGH,
F.
RUDD,
H.
STOCKING,
A.
I. WINNE,
Secretary, Virginia State Board of Pharmacy, Richmond.
Virginia.
L.
McGRAW -HILL
PUBLICATIONS IN PHARMACY
Jenkin. and DuM ez-QUANTITATIVE PHARMACEUTICAL CHEMISTRY
JordanQUALITATIVE ANALYSIS FOR STUDENTS OF PHARMACY AND MEDICINE
LynnPHARMACEUTICAL THERAPEUTICS
Speaa_
PHARMACEUTICAL MATHEMATICS
COPYRIGHT,
1931, 1937,
BY THE
THE
USE
IN
THIS
VOLUM!::
OF
CERTAIN
PORTIONS
OF THE
PERMISSION
RECEIVEO
FROM
SAID BOARD
OF TRUSTEES
INACCURACY OF
QUOTATIO....
STATEMENT
QUANTITIE:S
OF'
IS
NOT
NOR
OR
THE
PERCENTAGE
STRENGTHS.
ASSOCIATION~
viii
The wide popularity that the first edition of thi~ book has
enjoyed among students and teachers has been gratifying to the
publishers and to the authors. It is hoped that the new edition
will similarly commend itself to a still larger circle. To the many
kind friends who have so generously aided by means of helpful
suggestions, the authors desire to express their thanks.
GLENN L. JENKINS.
ANDREW G. DuMEZ.
MINNEAPOLIS, MINN.
BALTIMORE, MD.,
February, 1937.
MD.
December, 1930.
CONTENTS
PAGE
vii
ix
xix
II
29
GRAVIMETRIC METHODS . .
57
86
xu
CONTENTS
PAGE
105
116
CHAPTER
. . . . . . . . . . . .,129
Theory-Standard solutions-Preparation and stanaardization of
tenth-normal p'otassium permanganate.
Direct titration methods: Assay of ferrous sulfate, of reduced
iron, and of solution of hydrogen peroxide.
Indirect titration methods: Assay of calcium gluconate.
Residual titration methods: Preparation and standardization of
tenth-normal oxalic acid-Assay of sodium nitrite, of pre~
cipitated calcium carbonate, and of potassium chlorate.
Dichromate methods: Preparation of tenth-normal potassium
dichromate-Assay of mass of ferrous carbonate.
OXIDATION-REDUCTION METHODS .
CHAPTER IX
OXIDATION AND REDUCTION-IoDOMETRIC METHODS . . . . . . . . .
155
xiii
CONTENTS
PAGE
188
PART II
Pl5.ysical Methods Used in Official Pharmaceutical Analyses
CHAPTER XI
SOLUBI}!iITY.
203
..
207
l)efinitions.
Determination of the solubility of boric acid in water at 25C.
CHAPTER XII
SPECIFIC GRAVITY AND DENSITY .
226
xiv
CONTENTS
PAGE
CHAPTER XIV
REFRACTOMETRIC MEASUREMENTS .
. 240
247
Definitions-Polarimeters.
Determination of the specific rotation of sucrose.
CHAPTER XVI
. 257
VISCOSITY MEASUREMENTS.
. .
. .
. .
. .
. .
260
Colorimetry: Determination of the ammonia contellt of waterDetermination of the amount of epinephrine hyclrochlori1.e in
solution of epinephrine hydrochloride-Assay of crPCUS for color.
Nephelometry: Determination of the amount of arsep-ic trioxide in
solution of arsenous acid-Determination of the aJjlount of oil of
peppermint in spirit of peppermint and limit test for chloride an.d
sulfate in calcium gluconate.
CHAPTER XVIII
DETERMINATION OF HYDROGEN ION CONCENTRATION
......
272
CONTENTS
xv
CHAPTER XIX
ELECTROLYTIC ~ETHODS . . . . . . . . . . . . . . . . . . . . . 305
Electrical units and fundamentallaws-Theory-Apparatus.
Assay of copper sulfate and of mercuric chloride. Other electrolytic assays.
PART III
Special Methods
Use~
CHAPTER XX
ASH AND ~OISTURE DETERMINATIONS . . . . . . . . . . . . . . . 323
Ash content: Determination of the total and acid-insoluble ash
content of digitalis leaf.
~oisture content: Determination of the moisture content of acacia
-Determination of the moisture content of digitalis leaf by the
toluene distillation method.
CHAPTER XXI
ExTRACTIVE AND CRUDE FillER CONTENT . . . . . . . . . . . . . 336
Volatile and non-volatile ether-soluble extractive: Determination
of the volatile and non-volatile ether-soluble extractive of clove.
Alcohol-soluble extractive: Assay of benzoin.
Water-soluble extractive: Assay of aloe.
Purified petroleum benzin extractive.
Crude fiber: Determination of the crude fiber content of cloves.
CHAPTER XXII
CONSTANTS OF FATS, FATTY OILS, WAXES, BALSAMS, RESINS, ETC. . . 345
Acid number: Determination of the acid value of rosin.
Saponification value: Determination of the saponification value of
cottonseed oil.
Ester number.
Unsaponifiable matter.
Iodine value: Determination of the iodine value of olive oil.
CHAPTER XXIII
. . . . . . . . . . 361
ASSAY OF VOLATILE OILS
~ethods of general application: Specific gravity-Rotatory power
-Refractive index-Congealing point-Distilling point-Fractional distillation-Solubility.
Assay for ester content: Preparation of half-normal alcoholic potassium hydroxide-Assay of oil of peppermint for total esters.
Assay for alcohol content: Assay of oil of peppermint for total
menthol.
Assay for aldehyde content: Assay of oil of bitter almond for
benzaldehyde content.
xvi
CONTENTS
PAGE
386
403
Assay of opium.
Table of official substances assayed by the same met.hod as opium.
Assay of colchicum.
Table of substances assayed by the same method as colchicum.
Assay of nux vomica.
Assay of caffeine containing drugs:-Assay of guaranlt.
Table of official drugs and preparations assayed for caffeine.
Assay of alkaloidal salts: Assay of citrated caffeille, of eucaine
hydrochloride, of theobromine with sodium salicylate, and of
theophylline with sodium acetate.
418
CONTENTS
~vii
PAGE
CHA'pTER XXVII
OTHER OFFICIAL ASSAYS INVOLVING THE USE OF IMMISCIBLE SOLVENTS 437
Assay of cantharides-Assay of aspidium-Assay of jalap-Assay
of tablets of phenobarbital.
CHAPTER XXVIII
ASSAY OF ENZYME-CONTAINING SUBSTANCES . . . . . . . . . . . . 444
Assay of pepsin-Assay of pancreatin for starch digestive powerAssay of pancreatin for casein digestive power-Asflay of rennin.
TABLE OF LOGARITHMS AND ANTILOGARITHMS.
453
INDEX . . . . . .
457
INTRODUCTION
Quantitative pharmaceutical analysis may be defined as the
application of the procedures of quantitative analytical chemistry
to the analysis of the materials used in pharmacy and, especially,
to the determination of the purity and quality of the drugs and
chemicals official in the United States Pharmacopoeia and in the
National Formulary. A complete chemical analysis of any
substance requires the establishment of the identity of its
component parts by qualitative analysis and the determination
of the proportion in which these components are present by the
processes of quantitative analysis.
Quantitative chemical methods are commonly classified as
organic and inorganic j gravimetric, volumetric, gasometric, and
electrometric. It is impractical, however, to adhere strictly
to this classification in presenting the subject matter of quantitative pharmaceutical analysis since certain phases of the work, as
alkaloidal assaying and the assay of essential oils, have been
developed to a point where' they constitute a distinct subject
matter in which the principles involved and the technique
required are the same whether the procedure be gravimetric or
volumetric.
Quantitative pharmaceutical analysis may be appropriately
subdivided according to various procedures each of which requires
a special technique, as follows:
Gravimetric analysis, or the separation, by extraction, precipitation, or other means of the constituent to be determined
either in the natural state, or in the form of a definite compound
the composition of which is known to the analyst, and weighing
the resulting product.
Volumetric analysis, or the determination of the volume of a
solution of known concentration required to react with a given
amount of the substance to be analyzed.
Gasometric analysis, or the measurement of the volume
of a liberated gas or the decrease in volume of a mixture of
xix
xx
INTRODUCTION
INTRODUCTION
XXI
Calculations
1. HAMILTON and SIMPSON, "Calculations of Quantitative Analysis,"
2d ed., McGraw-Hill Book Company, Inc., New York, 1927.
2. LONG and ANDERSON, "Chemical Calculations," 3d I'd., McGraw-Hill
Book Company, Inc., New York, 1936.
3. MELLOR, "Higher Mathematics for Students of Chemistry and
Physics," 4th I'd., Longmans, Green & Company, New York, 1922.
4. MILLER, "Calculations of Analytical Chemistry," 3d I'd., McGrawHill Book Company, Inc., 1921.
5. MOORE, "Logarithmic Reduction Tables, for Students of AnaJytical
Chemistry," Ginn and Company, Boston, 1913.
xxii
INTRODUCTION
2.
3.
4.
5.
6.
7.
8.
INTRODUCTION
xxiii
xxiv
I NTRODUCT TON
INTRODUCTION
xxv
PART I
GENERAL METHODS USED IN OFFICIAL
PHARMACEUTICAL ANALYSES
CHAPTER I
REMARKS AND GENERAL DIRECTIONS
Success as an Analyst.-To be successful as an analyst, the
student must realize that analytical chemistry is not simple
routine procedure. Manipulative skill acquired by experience
with the ability to follow directions under the supervision of a
skilled analyst may enable one to carry out successfully certain
analytical procedures. The object of teaching quantitative
pharmaceutical chemistry, however, is to impart a thorough
fundamental knowledge of the theory as well as the practice of analytical methods.
The successful analyst must know what reactions are taking
place during an analysis and be able to understand and apply
the theory upon which the method is dependent. The analyst
must acquire skill of technique, patience, neatness, and accuracy.
The fact should be borne in mind that analysis is not carried out
for the sake of analysis but as a means to control the purity and
strength of substances used as medicaments. Above all, to be
successful, the analyst must not only use common sense in the
laboratory but think throughout each step of the procedure.
Accuracy and Honesty.-It is absolutely essential that all
quantitative work be performed without even a slight loss of
material or gain of extraneous matter. Every precaution should
be taken to prevent such loss or gain. All solutions and precipitates should be covered to prbtect them from dust, whenever
possible, and every particle of sample, solution or precipitate
must be regarded as indispensable to the ultimate success of the
analysis.
Absolute integrity is demanded of every quantitative analyst.
The operator is the only person who is familiar with the entire
history of an analysis and who knows whether it is worthy of full
confidence. When confidence is lost for any definitely established reason in the course of an analysis, operations should be
3
(3
Number of Packages
in Shipment
1 to 10
10 to 25
25to 50
50 to 75
75 to 100
Number of Packages
to Be Sampled
1 to 3
2 to 4
3to 6
6 to 8
8 to 10
10
M"gnitude of error
FIG. 2.-Probability curve.
+X
it is apparent that the best value to select for a series of observations is their arithmetical mean.
'
Average Deviation from the Arithmetical Mean.-In order to
measure the magnitude of indeterminate or accidental errors,
use is made of the theorem proved by the method of least squares
which states that an arithmetical mean computed from n equally
trustworthy observations is
times as trustworthy as any
single observation. If the indeterminate error in anyone observation is represented 'by i, the indeterminate error of the arithmetical mean is i/Vn; in other words, the uncertainty of the
arithmetical mean is inversely proportional to the square root
of the number of observations. The deviation of a single measurement from the arith~etical mean of a series of similar measurements can readily be determined and from this the average
deviation of a single determination may be calculated. For
example: (1) In the standardization of hydrochloric acid by
titration against pure sodium carbonate, the burette readings
30.25, 30.22, 30.26, 30.27, and 30.23 cc. were obtained. The
vn
11
12
13
mum apparent error in the result is 0.05 which is the greatest apparent error in the number 12.4. Therefore, a derived
error of 5 exists in the second decimal place, figure 6, of the
result and the1r"esult should be written 137.6 but if the result is
used for further calculations, it is better to retain one figure more
i.e., to employ 137.57.
In multiplication or division, as a rule, retain one more significant figure, when available, in the result than there are in the
number having the least number of significant figures. For
example: The product of 11.32 X 12.2 X 0.0321 = 4.4331384.
If the last figure in each number is uncertain, the relative error
in the number 12.2 will be about 5 in 1,200 or 0.4 per cent.
Consequently, it would be incorrect to write the result as
4.4331384 for this result has a derived error of 0.4 per cent or
of about 2; units in the second place of the decimals. All figures
following this are therefore meaningless and should be discarded,
the result. being written 4.43.
Logarithms and Their Use.-The solution of problems and
the calculation of the results of analyses from data are greatly
facilitatEld by the use of logarithms. It is advisable for students
to make calculations by the use of logarithms in order to save
time and avoid tedious calculations by long hand.
A lOgarithm is an exponent which must be applied to a fixed
positive number other than 0 or 1 to produce any given number.
The fixed number is called the base. In the common or Briggsian
system of logarithms, the base is 10. A logarithm consists of
twO' parts, the characteristic or integral part and the mantissa or
fractional part. The characteristic of a number greater than 1 is
always one less than the number of digits to the left of the decimal
point, i.e., where n equals the number of digits to the left of the
decimal point, the characteristic is represented by a number
equal to n - 1. For exampl~, the characteristic of 10,000 or
10 4 is 4, of 100 or 10 2 is 2, and of 1 or 10 0 is 0. The characteristic
may be either positive or negative. When there are no digits
to the left of the decimal point, the characteristic is negative or
minus, and when there are no zeros before the significant figures
to the right of the decimal point, the characteristic is -lor
9 - 10. When there are no digits to the left of the decimal
point and n zeros to the right of the decimal point before the
14
3.0000
7.5730 - 10
15
10.5730 - 10
16
17
18
19
20
has been burned away, rotating the crucible slightly from time
to time to expose fresh portions of precipitate. The crucible
containing the ignite'd residue is allowed to cool in a desiccator
and weighed. It is then ignited a second time and weighed. If
the successive weighings do not agree within 0.2 mg. when a
porcelain crucible is used, it should be ignited and weighed a
third time. These operations should be repeated until constant
weight is attained.
Constant Weight.-The. term dried to constant weight means
that two consecutive weighings do not differ by more than 0.1
per cent when the second weighing is made after an additional
hour of drying.
21
22
RIDER HOOK--__
STIRRUP-- __
------RIDER ROD
BEAMARREST--
STlRRUPHOOK---
GRAVITY WEIGHT
_____ COLUMN
____INPlCATOR
BowWIRES-
(OR. NEEDLZl
~ __ --.LEV)!:L
PAN---__
.---PAN ARREST
---INPEX PLATE
23
24
are then carefully lowered, and if the beam does not swing, it
may be set in motion by means of the rider. Long swings of the
pointer are not necessary. The pointer should swing through an
amplitude of not less than two divisions to either side of the zero
of the index scale.
11. All weights should be handled with the forceps; they should
never be touched with the fingers. Place heavy weights in the
center of the pan to prevent oscillation.
12. Record all weights directly into your notebook upon completion of a weighing. Before removing weights, check the
balance by arresting and releasing the beam and be sure that
correct balance has been attained. Remember that a slight error
in weighing may render worthless all further analysis of a sample.
13. Before leaving the balance, stop the motion of the beam
by means of the pan arrests, raise the beam off the agate knife.
edges, be sure the balance is clean, and close the door of the
balance case.
Sensitivity of the Analytical Balance.-The sensitivity varies
inversely with the weight of the beam. The lighter the beam,
therefore, the greater the sensitivity. The sensitivity varies
with the length of the beam. The sensitivity varies directly to
the time period of oscillation. The sensitivity varies inversely
with the load on the pans. The sensitivity of a balance may be
varied by moving the small gravity weight on the pointer upward
or downward, thus changing the position of the center of gravity
of the beam. The efficient'operation and sensitivity of a balance
are dependent upon minimum friction between the agate
knife edges and bearings.
Exercise 1
25
and divide t.he difference by two; the result gives the true zero point of the
balance.
The difference between the two rest points gives the sensitivity
of the balance in terms of index scale divisions. Assume that the
difference in the rest points is two, then 1 mg. causes a displacement of two scale divisions. Since the index scale can be read
to one-tenth of a division and there are 20 one-tenth divisions,
the balance is said to be sensitive to 0.05 mg.; that is, the smallest
weight which can cause a readable deflection is 0.05 mg.
Determine the sensitivity of the balance with loads of 10 Gm.
on each pan and with 20 Gm. on each pan. Tabulate your
results.
WEIGHTS
26
27
CALIBRATION CHART
Left
0 . 005
0.010
0 . 010
0.020
0 . 050
0 . 100
0.100
0 . 200
0.500
1.0
1.0
1.0
2.0
5.0
10.0
10 . 0
20 . 0
50.0
Right
Rider
0.005
0.01
0.01 + 0.01
0.02 + 0.01 + etc.
0.05 + 0.02 + etc.
O. 05
O. 02 + etc.
0 . 100 + 0 . 100
0 . 200 + etc.
0.500 + etc.
0.500 + etc.
0.500 + etc.
1 + 1
2+1+1+1
5+2+1+1+1
5+2+1+1+1
10 + 10
20 + 10 + 10 + etc.
Rider
reading
Actual
weight
Aliquot
Actual
part correction
+0 . 0050
+0 . 0052
+0 . 0001
-0 . 0002
+0.0042
+0 . 0045
+0 . 0044
+0 . 0008
+0.0044
+0.0040
+0 . 0024
+ 0.0034
-0 . 0014
0.0000
-0.0064
- 0.0052
-0.0024
-0 . 0032
0.0050
0.0102
0 . 0103
0.0203
0.0500
0.1003
0.1002
0.2013
0 . 5020
1.0036
1.0020
1.0030
2 . 0042
5.0128
10.0192
10.0204
20.0372
50.0992
0 . 0050
0.0100
0.0100
0.0200
0.0501
0.1002
0 . 1002
0.2004
0.5010
1.0019
1.0019
1.0019
2 . 0038
5.0096
10.0192
10.0192
20 . 0384
50.0950
0.0
+0.0002
+0.0003
+0.0003
+0.0001
+0.0001
0.0000
+0.0009
+0.0010
+0.0017
+0.0001
+0.0011
+0.0004
+0 .0032
0 . 0000
+0 . 0012
-0 . 0012
+0 . 0042
28
0.005
0.010
Correction,
0.1 mg.
0
+2
O.OlO
+3
0.020
0.050
0.100
0.100
0.200
0.500
+ 3
0
+ 1
0
+9
+10
Weight
1.0
1.0
1.0
2.0
5.0
10.0
10.0
20.0
50.0
Correction,
0.1 mg.
+17
+ 1
+11
+ 4
+32
0
+12
-12
+42
CHAPTER II
GRAVIMETRIC ANALYSIS
THEORY
30
chloride gas, and the hydrogen and chloride ions differ from
hydrogen and chlorine gas, respectively.
4. The ionization of the electrolyte results in an equilibrium.
The point at which equilibrium is reached is dependent on the
nature of the electrolyte, the nature of the solvent, and upon
the dilution; thus, electrolytes differ in the extent to which they
ionize; some solvents, such as ether and benzene, produce no
ionization, but in solvents which produce ionization, the greater
the dilution the greater the extent of ionization of the electrolyte.
A certain state of equilibrium exists between the ions and
undissociated molecules for every degree of dilution. The
equilibrium'''may be represented as follows: NaCI
Na+ + Clwhen sodium chloride is dissolved in water. Since the extent
of dissociation is dependent on dilution, the greater the dilution
of the solution the more sodium chloride will dissociate into ions
until at infinite dilution it may be regarded as completely ionized.
'l'b . .
db h
. [Na+J X [Cl-J
The eqUlI
num IS represente y t e equatIon
[NaCl]
=
31
GRAVIMETRIC ANALYSIS
and
32
Substance
Temperature,
C.
25
25
25
25
25
18
18
Ions involved
AIO,- X H+
BaH X CO,-Ba'+ X SO.-Ca++ X CO,-Ca++ X C,04-Pb H X CO,-Pb++ X S04--
18
18
25
25
25
25
25
25
Hg++
Hg+
Ag+
Ag+
Ag+
Ag+
25
X
X
X
X
X
X
S--
crBrCl1SCN-
Solubility
product
3.7
8.1
1.08
9.3
2.6
3.3
1
X
X
X
X
X
10-16
10'"
10- 1
10'"
10'"
2.5
X 10-13
3.4
2.6
4
3.5
7.7
1. 5
0.9
1. 2
X
X
X
X
X
X
X
X 10-14
X 10'"
10- 11
10'"
10-54
10- 18
10-1 '
1{)-10
10- 18
X 1{)-12
33
GRAVIMETRIC ANALYSIS
1 1 X 10-5
moles per liter. At this dilution the dissolved silver chloride may
be assumed to be completely ionized, AgOI~Ag+
01- so
that each mole of silver chloride furnishes 1 mole of silver ions
and 1 mole of chloride ions. The solubility product, S.P., then
= 1.2
X 10-1 ,
0.0~~~~8235 =
0.00000001
= 10-8
Assuming 100 per cent ionization at this dilution, the concentrations of Ag+ and of 1- also equal 10-8 , since each molecule of
34
AgI forms 1 Ag+ ion and 1 I- ion, and the solubility product is
equal to the ionic product
Ou+ X Ox- = 10-8 X 10-8 = 10-16 = S.P. of AgI
From the above calculation of solubility product, it can be
predicted that silver iodide will precipitate if Cu+ X 0 1- becomes
greater than 10- 16 ; that in a supersaturated solution Cu + X Oxbecomes greater than 10- 16 ; that in a saturated solution OAa+
X Ox- wilJ..be equal to 10-16 ; an(that to dissolve precipitated
AgI, OAa+ X 0 1- must be less than)O-16.
In the above illustration, the solubility product of silver iodide
was calculated from solubility data. Conversely, if the solubility
produce is known, the solubility of a compound may be calculated. In the table, the solubility product of silver chloride is
given as 1.5 X 10- 10 at 25C. How much silver chloride will
dissolve in 100 cc. of water at the above temperature?
S,P' AgCI = GAg+ X GCI- = 1.5 X 10- 10
If OAg+ = x,
then
OCl- = x,
since
OAg+
x 2 = 1.5 X 10-10
X = 1.22 X 10-5
= OCl-
10
GRAVIMETRIC ANALYSIS
35
+ Ol---l-AgOl ~
36
1. What are the postulates upon which the theory of ionization is based?
2. What is a reversible reaction?
3. What conditions tend to destroy equilibrium and cause a reaction to
go to completion?
4. Define and illustrate the solubility product priilCiple.
5. 0.247 mg. of barium sulfate dissolve in 100 cc. of water at 25C.
Express the solubility in terms of molar solubility.
6. From the solubility of BaSO. given in'problem 5 calculate its so_lubility
product assuming 100 pel' cent ionization.
7. The solubility product of calcium sulfate is approximately 2 X 10- 4
Calculate the amount of calcium sulfate soluble in 500 cc. of water. Assume
100 per cent ionization.
S. Illustrate how common ion effect may be utilized to secure quantitative
precipi tation.
9. A saturated solution of lead chloride at 20C. contains 0.07 mole per
liter. This solution is 80 per cent ionized. Calculate the solubility product.
CHAPTER III
GRAVIMETRIC METHODS
Gravimetric analysis implies that the substance to be determined is to be separated from a weighed sample in the form of a
compound of known composition and weighed. Knowing the
weight of the original sample and that of the product, the weight
and percentage of any component common to both can be calculated. The product to be weighed in pharmaceutical analysis
may be obtained by any'one of various methods: (1) It may be
precipitated from solution; (2) it may be the decomposition
product resulting from ignition of a compound; (3) it may be
deposited on an electrode by electrolysis; (4) it may be separated
from other substances by extraction with a solvent; and (5) it
may be obtained by absorbing a gas in some substance of known
weight and finding the increase in weight produced by the absorption of the gas. The first two methods comprise the subject
matter considered in this chapter.
Exercise 4
Determination of Chloride Ion in a Soluble Chloride.-Chloride
ion is determined gravimetrically by precipitating and weighing it
as silver chloride. An excess of solution of silver nitrate, slightly
acidified with nitric acid, is added to the solution of soluble chloride. The precipitate is filtered out, washed, dried, and weighed
as silver chloride. Other substances which yield insoluble silver
salts must be absent.
No method for the gravimetric determination of chloride ion is
official, but the procedure constit.utes a classic example of gravimetric analytical technique with which every student should be
familiar.
Object.-Assay of Sodium Chloride.
Materials Required.-O.25 Gm. of sodium chloride.
5 per cent silver nitrate solution.
37
38
The solution is acidified with nitric acid to prevent the precipitation of other substances insoluble in water but soluble in nitric
acid such as carbonates, oxides, and phosphates. The acid also
helps to coagulate any colloidal silver chloride. Too great an
excess of nitric acid must not be added, since it exerts some solvent action on silver halides. The acidified solution should not
be heated until the silver nitrate has been added, since chlorine
may be liberated and lost, thus:
NaCl
6HCl
+ 2HN03~3C12 + 4H 20 + 2NO
39
+ NaCl---+AgCl t + NaNOs
40
Weight of
II
14.3580
14.0420
0.3160
18.2468
19.0204
19.0201
19.0200
18.2468
0.7732
14.0420
13.7315
0.3105
17.8827
18.6409
18.6403
18.6402
17.8827
0.7575
41
42
Exercise 5
Determination of Sulfate Ion in a Soluble Sulfate.-The
sulfate ion in a soluble sulfate may be determined gravimetrically
43
44
Substance
Weight
of
Ignition
sample, residue
Gm.
--U.S.P.
Lead 8ubaceta teo R ..........
Sodium sulfate ..............
Sulfur ointment ..... ........
R.
1.0
0.4
0.5
1.0
PbSO. .......
BaSO. 0.6086
BaSO. 0.1373
BaSO. 0.1373
1.0
1.5
1.0
0.6
0.5
BaSO.
BaSO.
BaSO.
BnSO.
BaSO.
0.5661
0.1373
1.03757
0.7465
0.6086
Pb = 70 to 73
Na.SO. = 99
S = 13.5 to 16.5
S = 99.5
(NH.),SO. = not more than 8
S = 10
C.H 3.OH.OCH 3SO.K = 97
K,SO. = 99
Na,SO. - 99
reagent.
;:~:~~
45
Exercise 6
Determination of the Mercury Content of a Mercuric Salt.The mercury is precipitated as sulfide, washed, dried, and
weighed.
Object.-Assay of Mercuric Chloride.
Materials Required.-O.5 Gm. of mercuric chloride.
1 cc. of hydrochloric acid.
About 70 cc. of alcohol.
About 40 cc. of carbon tetrachloride.
Procedure.-l. "Dry about 0.5 Gm. of Mercury Bichloride to constant
weight over sulfuric acid, weigh accurately, and dissolve in 300 cc. of warm
distilled water to which 1 cc. of hydrochloric acid has been added. Pass
hydrogen sulfide through the cold solution until the precipitate of ~ercuric
sulfide readily subsides, leaving a clear, supernatant liquid."
46
47
The reactions which occur may be represented in their simplest form by the following equation:
,
HgCh
H2S~ HgS
2HCI
271.52 34.08 232.67 2(36.47)
The same principles are employed for the estimation of mercuric oxide in ointment of mercuric oxide and for the determination of the mercury content of such compounds as ammoniated
TABLE III.-:OFFICIAL SUBSTANCES ASSAYED "BY PRECIPITATION AS
SULFIDE
Substance
Sample,
ResiGm. or
due
cc.
Factor
Official requirement,
per cent
---U.S.P.
Bismuth and potassium tartrate .....
Merbaphen .........
Mercuric chloride,
poison tablets of,
large .......... , .
Mercuric chloride,
poison tablets of,
small ............
Mercuric chloride ...
Mercuric oxide, ointment of ..........
Mercury, ammoniated .............
Mercury, ammoniated, ointment of.
0.4
0.5
10
HgS
20
0.5
HgS
HgS
10
HgS
0.931
0.5
HgS
0.8622 Hg = 78 to 80
1.5
HgS
0.862
3.0
Hg = 7.1 to 8.7
N.F.
Bismuth, glycerite of
Number of tablets .
Grams per tablet.
48
Exercise 7
Determination of the Purity of Calcium Glycerophosphate.The calcium is precipitated as oxalate, ignited, and weighed as
oxide.
Object.-Assay of Calcium Glycerophosphate.
Materials Required.---O.4 Gm. of calcium glycerophosphate.
20 cc. of 5 per cent acetic acid.
Ammonium oxalate T.S. (3.5 Gm. ammonium oxalate in 100 cc.).
Procedure.-l. "Dry about 0.4 Gm. of Calcium Glycerophosphate to
constant weight at 130C., weigh accurately, dissolve in 20 cc_' of an aqueous
solution of acetic acid 1 in 20, and add 30 cc. of distilled water. Heat the
mixture to boiling, and add an excess of ammonium oxalate T.S."
49
GRAVIMETRIC METHODS
+ 2CHaCOOH---+Ca(CHaCOO)2 +
CaH 5 (OH)2H 2PO 4
210.15
Ca(CHaCOO)2
+ (NH4)2C20C-+CaC204 + 2CHaCOONH 4
CaC 20c-+CaO + CO 2
56.08
+ CO
50
Exercise 8
Determination of the Aluminum Content and Purity of Alulll.The aluminum is precipitated as hydroxide, ignited to oxide,
and weighed.
Object.-Assay of Alum.
Materials Required.-l Gm. of alum.
1 Gm. of ammonium chloride.
Ammonia T.S.
Procedure.-" Dissolve about 1 Gm. of Alum, accurately weighed, and
about 1 Gm. of ammonium chloride in 250 cc. of distilled water. Heat the
solution to boiling, and Mid a slight excess of ammonia T.S. to precipitate
aluminum hydroxide. Collect the precipitate on a filter, wash thoroughly
with hot distilled water, dry, ignite strongly, and weigh. The weight of
the aluminum oxide so obtained, multiplied by 8.894, indicates its equivalent
in Al'NH.(S04)2.12H 20 and when multiplied by 9.307, indicates its equivalent in AlK(SO.):.12H 20."
51
Substance
Sample,
FacOm. or Residue
tor
cc.
- - - --U.S.P.
Alum, ammoniUDl .......
Alum, ammoniuOl, exsiccated ...............
Alum, potassium ........
Alum, potassium, exsic...
cated ................
Bismuth subcarbonate ...
Bismuth subgallate ......
Bismuth subnitrate .....
Bismuth subsalioylate ..
Calcium creosotate ......
Zinc ac.tate ............
Zinc chloride ............
Zinc oxide, ointment of ..
Zinc suifate .............
N.F.
Aluminum acetate, solution of ...............
Aluminum chloride ......
Aluminum chloride, solution of. ..............
Aluminnm subacetate,
solution of ............
Aluminum sulfate .......
Bismuth magna ........
Bismllth subcarbona.te,
tablets of .............
Bismuth SUbgallate, tablets of
Bismuth subnitrate, tablets of ................
Bismuth subsalicylate.
ampuls of .............
Calcium glycerophosphate
Manganese citrate. soluble
Manganese glycerophosphate ................
Zinc phenolsulfonate ...
1.0
AhO.
8.894
AINH.(SO.),.12H,O = 99.5
0.5
1.0
AhO.
AhO.
4.653
9.307
0.5
1.0
1.0
1.0
1.0
0.2
1.0
1.0
2.0
1.0
AhO.
BisO.
Bi,O.
BitO.
BhO.
CaO
ZnO
ZnO
ZnO
ZnO
5.066
AIK(SO.), = 96.5
BhO. = 90
Bi,O. = 52 to 57
.BhO, - 79
BhO, - 62 to 66
CaO = 40 to 50
(CH,COO),Zn ~ 83.16 to 87.32
ZnCh - 95
ZnO = 19 to 21
ZnSO. = 55.86 to 58.63
5.0
0.5
AhO.
AhO.
5.0
AhO.
4.737
5.0
0.5
10.0
AbO.
Al,O,
BilO.
3.0-
Bi,O.
...... Bi,O.
= 83 to 97 b
a.o
Bi,O.
...... Bi,O.
= 48 to 6]0
3.0
BilO.
......
1.0
0.4
0.5
0.5
2.0
Mn.O, 2.95
MnC,H.(OHhPO. = 98
ZnO
6.8284 Zn(C,H.OSO.) . 8H,O = 99.5
......
......
......
......
......
2.254
1.674
......
1.984
BhO. = 73 to 85'
52
2AINH.(SO')z.12HzO
2 X 453.32
101.94x = 906.64
x = 8.894 Gm. alum equivalent to 1 Gm. AlzO a
Calculate the purity of the alum and the per cent of aluminum
in the sample.
Questions and Problems
1. Why is ammonium chloride added to the alum solution previous to
precipitation?
2. Why should a large excess of ammonium hydroxide be avoided?
3. Indicate by reactions how ammonium salts in solution may become
acid in reaction upon prolonged boiling.
4. If an unknown sample of alum yields 0.125 Gm. of Al z0 3 upon assay, to
how much AINH.(SO.)z.l2HzO, AINH.(SO.)" and AIK (SO.)z. 12H zO,
respectively, is the Al 20, equivalent?
6. A 3.0000 Gm. sample prepared by powdering 20 tablets of bismuth
subnitrate which weighed 6.8420 Gm. yielded 2.3687 Gm. of Bi z0 3 Calculate the amount of Bi and of BizO. contained in each tablet. Calculate the
per cent of Bi and of Bi z0 3 contained in each tablet.
6. Write equations for the reactions that take place in the assay of ointment of zinc oxide.
7. How much pure zinc sulfate would be required to form 0.8920 Gm. of
ZnO?
8. A sample of soluble manganese citrate weighing 0.5624 Gm. yielded
0.2744 Gm. of Mn 30.. What per cent of manganese did the sample contain?
Exercise 9
GRAVIMETRIC METHODS
53
from excessive carbon dioxide by repeatcd pouring. Add 100 cc. of distilled water, 2 cc. of hydrochloric acid, 20 cc. of sodium phosphate T.S.,
and 2 drops of methyl red T.S. Add ammonia T.S a few drops at a time
with constant stirring until the solution becomes faintly yellow. Allow the
mixture to stand for ten minutes, add 40 cc. of stronger ammonia T.S. with
constant stirring, and allow the mixture to stand for two hours or over night."
+ H 2P04"
+ HPO,
+ PO:'
54
+ 2NHa + 13H 20
2(40.32)
222.68
Substance
Sample,
Gm. or
co.
Official requirements,
per cent
Residue Factor
--
U.S.P.
Magnesium citrate, solution
of ............
Magnesium sulfate ..... " ...
Sodium phosphate .........
Sodium phosphate, exsiccated .........
N.F.
Magnesium sulfate, ampuls of
Sodium phosphate, solution
of ............
10.0
= 1.6 to
1.9W IV
= 99.5
1.0
Mg~20r
0.3
Mg 2P 2Or 1.275
Na.HPO.
= 98
0.2
Mg 2P 2Or 1.275
Na,HPO.
= 98
0.20
5.0
Mg 2P 2Or 1.275
1.081
MgSO.
Na,2HPO.
= 39 to
105~
41 W IV
55
Substance
Sample,
Gm. or
Residue
ee.
U.S.P.
Collodion ............. 10.0
Camphor, liniment of ..
5.0
Camphor. spirit of. .... 25.0
Erythrityl tetranitrate,
diluted.
Gold chloride, R ......
Iodine, compound, 80lution of (for KI) ......
Iodine, tincture of (for
KI) ...................
Iodine. tincture of, mild
(for NaI) ...........
Molybdic anhydride, It.
Palladous chloride, R ..
Platinic chloride, R ....
N.F.
Camphor, ampule of ...
Phenolphthalein, tahlets
01 ..................
Pyroxylin ~ 5.1 W IV
Camphor ~ 19 to 21
Camphor = 9.5 to 10 5 W IV
0.2
Pyroxylin
Cottonseed oil
Camphor dinitrophenylhydrazide
Erythrityl tetranitrate
Au
Au
= 47
5.0
KI
KI
= 9.5
5.0
KI
KI
= 4.5 to 5.5WIV
5.0
0.5
0.2
0.5
Nal
PbMoO.
Pd
Pt
5.0
Ampul oil
Camphor
0.65"
Phenolphthalein
0.25
C.H,(NO.)<
47 to 53
to 10.5 W IV
....
= 93 to 103&
are formed by zinc, cadmium, and manganese. Under carefully controlled conditions, the same general principles may be
made the basis for the estimation of cadmium, manganese,
phosphorus, zinc, and arsenic.
~uestions
and Problems
1. Explain each step in the procedure for the assay of sodium phosphate
and write equations for all reactions that take place in the assay.
2. What is magnesia mixture T.S.?
8. Under what conditions is Mg++ precipitated as MgNH 4P0 4.2H zO?
56
4. In the assay of ampuls of magnesium sulfate labeled "each 2 cc. contains 1 Gm. of magnesium sulfate," how would you sample a shipment containing 1 gross of ampuls? How much of the ampul solution would you
measure for each assay sample? What minimum and maJ[imum amounts of
magnesium sulfate might the ampuls contain in each cubic centimeter and
meet the official tolerance requirements?
5. A sample of sodium phosphate weighing 0.3666 GIn., when dried to
constant weight at 110C., weighed 0.1942 Gm. and upon assay yielded
0.1491 Gm. of Mg 2P 207. Calculate the per cent of sodium phosphate and
of phosphorus in the original sample and in the moiBturefree sample.
What per cent of moisture did the original sample contain?
CHAPTER IV
PRINCIPLES OF VOLUMETRIC (TITRIMETRIC)
ANALYSIS
58
59
60
61
2 cc.
0.006
0.30
5 cc.
0.01
0.20
10 cc.
0.02
0.20
25 ce.
0.03
0.12
62
50 ee.
0.05
0.10
63
64
65
5. A volumetric flask calibrated to contain 100 cc. at 25C. and 760 mm.
barometric pressure is used at 18C. and 746 mm. barometric pressure.
Calculate the volume of water contained in the flask at the temperature
and pressure at which it is used.
66
\0-
67
Since the
= - 4
= 4
= 4
=4
68
CRaCOOR
NaOR
+ CRaCOO+
OR- + Na+
R+
(2)
11(3)
ROR
11(4)
+ CRaCOONa
69
HCI
NaOH
+ CI+
OH- + Na+
H+
(2)
~ il(3)
HOH
11(4)
NaCI
Upon mixing the two solutions some Na+ and CI- ions unite
forming NaCl molecules-reaction (4). Water is only slightly
70
ionized, so nearly all of the H+ ions and OH- ions unite to form
HOH molecules-reaction (3). The removal of H+ and OHions in reaction (3) causes reactions (1) and (2) to proceed to
completion, so that if equivalent quantities of HOI and N aOH
are employed, the final solution will contain only HOH, a small
quantity of undissociated N aCI molecules and N a+ and Cl- ions.
If one of the products of a reaction is removed the reaction
proceeds to completion readily; e.g., when KNO a in solutio:p. is
treated with HCI solution the equilibria represented by: equations
(1) and (2) exist prior to their admixture.
(1)
KNO a
K+
(2)
HCI
Cl-
+NOa
+H+
U(3)
U(4)
KCl
HNO a
When the two solutions are mixed, equilibria become estaplished between the four reactions represented. If the solution
is boiled, HNO s is volatilized as fast as it is formed in reaction (4),
removing H+ and NO; ions, thereby causing reactions (1) and
(2) to go to completion. Upon evaporation of all of the water,
KCl remains.
Under Precipitation Methods numerous examples will be
encountered of the use of an excess of one component of a reaction
and of the removal of one of the products in the form of an insoluble precipitate as methods of forcing reactions to completion.
Indicators.-The indicators commonly used to determine the
end point in neutralization processes are as a rule complex
organic compounds capable of existing in t~o forms of different
color which are mutually convertible, one into the other, at
given H+ and OH- ion concentrations. Three theories have
been proposed to explain the change in color of indicators which,
briefly stated, are as follows:
'
1. The physico-chemical theory attributes the color to certain
ions an increase of which causes the appearance of a new color,
and the decrease of which causes the disappearance of a color or
the appearance of a different color.
71
Color
Indicator
pH range
5.2to6.8
3.0to4.6
6.0 to 7.6
4.8 to 6.2
3.0 to 5.0
4.5 to 8.3
3.1 to 4.4
4.2 to 6.3
6.8to8.4
8.0 to 9.8
8.0 to 9.6
Acid
Alkaline
Yellow
Yellow
Yellow
Yellow
Blue
Red
Pink
Red
Yellow
Colorless
Yellow
Purple
Bluish violet
Blue
Lilac pink
Reddish yellow
Blue
Yellow
Yellow
Red
Red
Blue
This table shows that methyl orange exhibits _its acid color,
pink, at a pH of 3.1 and its alkaline color, yellow, at a pH of 4.4,
while between these pH values the color undergoes transition
from one shade to the other. At a pH of 4.4 the solution is
slightly acid, since at neutrality pH = 7.
It would appear that an indicator which changes color exactly
at the neutral point, pH = 7, would be required in every case,
but this is not true. When a strong acid, such as hydrochloric
acid, is titrated with a strong base, like sodium hydroxide, the
change in concentration of hydrogen ion becomes very rapid as
72
73
74
75
Two to four drops per 100 cc. of reaction solution are employed
in titrations.
The color ({hange is very sharp if too much indicator is not
used. Meth:lll orange is used frequently in the titration of strong
acids and strqng alkalies and especially in the titration of weak
bases, e.g., NH 40H. It is also a good indicator to use in the
titration of th'e salts of weak acids such as carbonates, borates,
sulfides, etc., with a strong acid, since in these cases the acids
liberated in t~e titration reaction are too little ionized to affect
the indicatorj It does not give the proper end point in the titration of alkal6ids or organic acids. This indicator should never
be employe~ in the titration of alcoholic solutions, hot solutions,
or very dilnte solutions.
Methyl Red. o-Carboxy-benzene-azo-dimethyl-aniline.-The
indicator(solution is prepared by dissolving 0.10 Om. of the dry
dye in 1.00 cc. of 95 per cent alcohol. Two to four drops of the
resulting solution are used per 100 cc. in titrations. Methyl
red in{licator is especially useful in titrating ammonia, weak
bases, ,and alkaloids, but it is not suitable for the titration of
weak organic acids.
Phenol Red. Phenol-sulfon-phthaJein.-The indicator solution ,Is prepared by triturating 100 mg. of the dry powder in a
mor-ar with 14.5 cc. of 0.020 N NaOH until solution is complete
and <liluting the resulting solution to 250 cc. with recently boiled
distilled water. After the removal of any precipitate formed
upOll dilution, the solution is ready for use. In titrations, 3 to
6 drops of this indicator should be used for each 100 cc. of
sollJtion.
lfhenolphthalein indicator solution is prepared by dissolving
1 Gm. of phenolphthalein in 100 cc. of 95 per cent alcohol. Two
to three drops of this indicator should be used per'100 cc. of solution in titrations unless otherwise directed.
Phenolphthalein is an excellent indicator to use in the titration of weak organic and inorganic acids, most alkalies, and alkali.
salts, but it is not satisfactory for use in the titration of ammonia, alkaloids, or cold solutions of carbonates and bicarbonates.
It fimctions well in alcoholic solutions.
Thymol Blue. Thymol-sulfon-phthalein.-The indicator solution is 'prepated by dissolving 40 mg. of the dry substance in
76
77
78
79
Exercise 10
Preparation and Standardization of Hydrochloric Acid Solution.-Normal hydrochloric acid solution may be standardized
against pure sodium carbonate, standard solution of sodium
hydroxide, or gravimetrically by precipitating and weighing the
chloride ion as silver chloride.
Object.-To Prepare and Standardize Normal Hydrochloric
Acid.
Materials Required.-Hydrochloric acid.
4 Gm. of anhydrous sodium carbonate.
Procedure.-l. Dilute 95 cc. of hydrochloric acid with sufficient distilled
water to make 1,000 cc., and mix thoroug}lly.
80
When titration is complete, read the burette accurately and record the
volume of acid used in the titration.
10~99
require:
53 : 1,000: : 1. 6250 : x
1625.0
x = ---s3 = 30.66 cc.
Since only 30.20 cc. of acid were required in the titration, it is
evident that the acid solution is stronger than normal, and the
factor is 30.66/30.20 = 1.0152 N. The bottle containing the
acid should be labeled 1.0152 N HCl.
The calculation may also be made by the method of equivalents, namely,
Na 2 CO a + 2HCI = 2NaCI + H 2 0 + <t0 2
2) 105.99
2)72.94
36.47 = 1,000.cc. N HCI
53 Gm.
0.053 Gm. Na 2CO a = 1 cc. of N HCl, and 1 Gm. of Na 2CO a is
equivalent to 1,000/53 = 18.87 cc. of N HCl. Therefore,
1.6250 Gm. will require 1.6250 X 18.87 = 30.66 cc. of N HCI, and
30.66/30.20 = 1.0152 N, the factor of the acid. The solution
may be used for all practical work as standardized, the number
of cubic centimete!s used being multiplied by the factor to reduce
the solution to terms of exact normality.
If an exactly normal solution is wanted, the dilution required
may be calculated as follows:
30.66 - 30.20 = 0.46 cc. of water to be added to each 30 2 CC.
of the standard solution to make it exactly normal. To make
1,000 cc. of normal solution, it would be necessary to dilute with
water in the ratio, 0.46: 30.66: :x: 1,000 = 15.00 cc. of water in
1,000 cc. of the diluted solution. Measure 15.00 cc. of distilled
81
water into a dry 1,000 cc. flask, fill to the mark with 1.0152 N
Hel, mix the solution well, and verify the normality of the solution by titratiQn agamst weighed samples of sodium carbonate.
Volumetric solutions of hydrochloric acid may be standardized
gravimetrically by determining the amount of chloride ion
present as silver chloride, as described under gravimetric determination of ch~orides, using 10 cc. portions of the acid as samples.
Ten cubic centimeters of N Hel is equivalent to 1.4334 Gm. of
Agel. If a 10 cc. portion of acid is found to yield 1.4634 Gm. of
Agel, the acid is 1.4634/1.4334 = 1.0210 normal.
Solutions of hydrochloric acid may also be standardized by
titration against standard solutions of KOH or NaOH. Thus _ii
25.20 cc. of 0.9505 N NaOH is required to exactly neutralize
25.00 ce. 9f acid, the factor of the acid is 25.202~0~9505 = 0.9531
normal.
The normal solution is too strong for many assay procedures,
so 0.5 N, 0.2 N, 0.1 N, etc., solutions are employed. These may
be prepared by dilution of the normal solution in the proper _
ratio, but the resulting solution should always be restandardized.
Standard solutions of hydrochloric acid preserved in tightly
stoppered, alkali-free, glass bottles retain their strength indefinitely.
Exercise 11
Preparation and Standardization of Alkali Solutions.-Solutions of sodium hydroxide or potassium hydroxide may be
standardized against standard solution of hydrochloric or sulfuric acid or by titration against an accurately weighed quantity
of pure potassium bitartrate or potassium biphthalate.
Object.-To Prepare and Standardize Normal Sodium Hydroxide Solution.
Materials Required.-About 50 Gm. of sodium hydroxide.
A saturated solution of barium hydroxide.
A standardized solution of hydrochloric acid.
Procedure.-l. Weigh about 50 Gm. of sodium hydroxide on a rough
balance and dissolve it in about 1,000 cc. of distilled water. Add slowly
with stirring a sat~rated solution of pure barium hydroxide until no further
precipitation occurs (2 to 3 cc.). Allow the precipitate to subside for about
10 hr. and decant the liquid through a filter into a hard glass bottle or a
82
bottle the inside of which has previously been coated with paraffin. Close
the bottle tightly with a rubber stopper provided with a soda-lime tube.
83
+ NaOH-KNaC H
4
06
+H
40.00
+ CO 2-BaC0 + H 20
3
84
85
CHAPTER V
ALKALIMETRY
Alkali hydroxides and carbonates, etc., are usually titrated
directly with standard solutions of hydrochloric or sulfuric
acid using methyl orange as indicator. Phenolphthalein and
methyl red when used as indicators in such titrations are affected
by the acidic carbon dioxide liberated during titration so that the
end point appears before neutralization is complete. If phenolphthalein is used as indicator, carbonates must be removed by
precipitation before titration, or the titration mixture must be
boiled to expel the carbon dioxide formed during titration.
Direct titration is conducted by adding a standard reagent
solution in measured quantity to a substance in solution until the
end point, as shown by a change of indicator color, is reached.
Substances which are insoluble in water or which do not yield
a sharp end point that coincides with the stoichiometric point
upon direct titration are titrated residually.
Residual titration is conducted by treating the substance under
analysis with an amount of standard solution knorvn to be in
excess of that actually required to react with it completely;
the amount of standard solution in excess is then determined by
titration with another standard solution.
Exercise 14
ALKALIMETRY
87
88
+ H2S0r--~Na2S04 + 2H 20
98.08
142.05
2. "Add 3 drops of methyl orange T.S., and continue the titration until
the production of a permanent pink color. Each cubic centimeter of total
sulfuric acid consumed is equivalent to 0.0400 Gm. of NaOH. Each cubic
centimeter difference between the number of cubic centimeters of normal
sulfuric acid consumed in the methyl orange and phenolphthalein titrations
is equivalent to 0.1060 Gm. of Na 2CO a."
The base NaHCO a is practically neutral toward phenolphthalein because the hydrogen ion concentration of the weakly
ionized HCOa ion (HCO a H+
C03') is about the same
(1 X 10- 9) as that necessary to change the color of this indicator.
A minute amount of H 2S0 4 is sufficient, therefore! to indicate a
neutral solution by the discharge of the pink color. When methyl
orange is used as indicator, it does not change color from alkaline
to acid until a hydrogen ion concentration of about 1 X 10- 4
is obtained. This will occur only when all of the bicarbonate
has been neutralized. The reaction is indicated by the equation:
+ 2C0 + 3H 0
2
The volume of
ALKALIMETRY
89
The sodium salicylate reacts with the added acid to form free
salicylic acid and sodium chloride as follows:
C 6H 4.OH.COONa
160.04
+ HCl~C6H4.0H.COOH + NaCl
138.05
gO
91
ALKALIMETRY
II
~
'"
~~~~~oo
00
~o
00
oooo~~~~~~~oo~ooooo
OO~~~~OO~O~~OO~~OOMO~O
~~_~~~OO~~~~OO~~~~OOO
OOOO~OO_OO_OOO_OO_O
"''''
O')O)_OO...-lOOCl':l __ "'f4
O'lIO)~"""MO<XlOOOOO~
C_Ol~"I:I"o)Q:lOO~c.oO':>
CO ............ tQ<OOOOOO~_O)
00000000_000
0000000000000000000 000000000000
~OOOOO_OOOO~OtQOOOOtQ
O~~~~~O~~~~O~O~~~~O
lr.Il.t:I
O~~_
'"
1Q
10
C'H'QG"IG"IC"I_
C"I
lQl1':I_OOO _ _ tO __ lO
000""';""';""';000000
92
~\~~oo
ZnO
H2S04~ZnS04
H 20
81.38
H 2S04 + 2NaOH~Na2S04 + 2H 20
=
93
ALKALIMETRY
Materials Required.-2 Gm. of potassium and sodium tartrate.
The salt is heated slowly at first, since the sample swells and
fuses with concomitant decomposition. If strong heat is applied
in the initial stages of ignition, there may be loss of a portion of
the sample through decrepitation or spattering. After the mass
in the crucible is partially charred and white fumes are no longer
evolved, it is ignited to dull redness. If heated too strongly or
if the flame comes in contact with the carbonized mass, the alkali
carbonate may be converted into the oxide.
2. "After allowing the carbonized mass to cool, disintegrate it with the
aid of a stout glass rod and transfer thc mass and crucible to a beaker. Add
50 cc. of distilled water and 50 cc. of half-normal sulfuric acid, cover the
beaker with a watch glass and boil the contents for thirty minutes. Then
filter the solution and wash the residue with hot distilled water until the
washings cease to redden blue litmus paper. Now determine the residual
acid in the cooled filtrate by titration with half-normal sodium hydroxide,
using methyl orange T.S. as the indicator. The volume of half-normal
sulfuric acid consumed, multiplied by the proper equivalent of the salt,
represents the quantity of the salt present in the quantity taken."
210.12
+ 3C0 2 + 2H20
\.
KNaCO a + H2S04~KNaS04
122.1
98.08
+ CO 2 + H 20
94
The U.S.P. requires that potassium and sodium tartrate contain not less than 99 per cent of KN aC 4H 40 S Calculate the
purity of the sample analyzed and compare the result with the
U.S.P. requirement.
Questions and Problems
1. Why cannot the alkali salts of such acids as citric, tartaric, etc., be
titrated directly with a strong acid, in the same manner as soluble carbonates
are titrated?
2. How much,of each of the following salts is equivaldnt to 1 cc. of 0.5
N H,.sO.? (a) KHC.H.O s, (b) K aC sH.0 7.H 2 0, (c) CH,COONa, (d)
LisC GH,07. 4H 20.
3. Name a number of official substances assayed by the above method.
Exercise 19
ALKALIMETRY
95
of the soluble magnesium sulfate. The excess acid is then determined by residual titration with normal sodium hydroxide, using
methyl orange as 'indicator.
The reactions which take place when the magnesia magma is
dissolved and upon residual titration are as follows:
'Mg(OHh + H 2SOc---+MgS0 4 + 2H 20
58.34
H 2S0 4 + 2NaOH~Na2S04 + 2H 20
Each cubic centimeter of N H 2S0 4 consumed by the magma is
equivalent to:
58.34
2 X 1,000 = 0.02917 Gm. Mg(OH)2
If a sample of magnesia magma weighing 5.2430 Gm. when
dissolved in 25 cc. of 0.9915 N H 2S0 4 required 9.85 cc. of 1.1402
N NaOH to titrate the excess acid, the per cent Mg(OH)2 in
the sample could be calculated from the following formula:
[Ccc. H 2S0 4 X N) - (cc. NaOH X N)] X equivalent
Wt. of sample
Exercise' 20
Object.-Assay of Methenamine.
96
97
ALKALIMETRY
Exercise 21
+ NaOH~CHaCOONa + NHa + H 0,
2
distils with water when the flask is heated. The NHa is conducted into a receiving flask which contains an excess of N
H 2S0 4 The condenser should be fitted tightly with an adapter
~n such a manner that the distillate will be collected beneath the
surface of ,the standard acid. This is done to prevent loss of
NHa from the distillate. As soon as the NHa in the distillate
comes into the receiving flask, it combines with the H 2S0 4 to
forni (NH 4 )S04,
2NHa
17.03
+ H2S04~(NH4)2S04
132.14
98
Estimation of Nitrogen by the Gunning-Kjeldahl Method.Several methods have been developed for the so-called moist
combustion of nitrogen. The Gunning-Kjeldahl method which
will be described here, because it is the method specified in the
National Formulary for the estimation of the nitrogen content
of beef extract, illustrates the general principles involved in the
determination of nitrogen by all modifications of the Kjeldahl
method. See also peptone and casein, reagent, U.S.P.
The U.S.P. gives the following directions for the determination
of total nitrogen by the Kjeldahl method:
"Nitrates and Nitrites Absent.-Place about 1 Gm. of the substance, accurately weighed, in a 500-cc. Kjeldahl flask of hard
glass. The material to be tested, if solid or semi-solid, may be
wrapped in a sheet of nitrogen-free filter paper for convenience
in transferring it to the flask. Add 10 Gm of powdered potassium sulfate or anhydrous sodium sulfate, 0.5 Gm. of powdered
cupric sulfate, and 20 cc. of sulfuric acid. incline the flask at an
angle of about 45 and gently heat the mixture, keeping the
temperature below the boiling point of the mixture until frothing
has ceased. Increase the heat until the acid boils brliskly, and
continue the heating until the solution has been' clear green in
color for thirty minutes. Allow the mixture to cool, add 150 cc.
of distilled water, thoroughly mix the contents of the flask, and
cool again. Add cautiously 100 cc. of a 30 per cent aqueous
solution of sodium hydroxide added so as to cause the solution to
flow down the inner side of the flask to form a layer under the
acid solution. Add a few pieces of granulated zinc, connect the
flask, by means of a Kjeldahl connecting bulb, with a condenser,
the delivery tube from :which dips beneath the surface of a mixture
of 30 cc. of half-normal hydrochloric or sulfuric acid and 25 cc.
of distilled water contained in an Erlenmeyer flask or a widemouth bottle of about 500-cc. capacity. MiX; the contents of the
Kjeldahl flask by gentle-rotation, and distil until about two-thirds
of the contents of the flask has distilled over. Add about 5 drops
of methyl red T.S. to the contents of the receiving flask and determine the excess of acid by titration with half-normal sodium
hydroxide. Run a blank test and make necessary corrections.
ALKALIMETRY
99
100
lOi
ALKALIMETRY
temperature of 1050. The weight of the residue from 10 cc. of the solution
corresponding to 1 Gm. of extract of beef should not be less than 0.75 dm.
corresponding to 75 per cent of total solids in the original extract.
0.~2
X 10 = 13.9 cc.,
"102
opening so that the free flame will come in direct contact with the bottom
of the flask. Heat below the boiling point for about 10 min. or until frothing
has ceased and then raise the temperature and boil the mixture until the
latter acquires a pale straw color or is nearly colorless.
103
ALKALIMETRY
Amount
used,
Gm. or
Substance
cc.
Indicator
Official requirements,
per cent
Glyceryl
trinitrate, tablets of.
Magnesia magma.
Magnesium
M.R.
0.5
0.008515 NH,
M.R.
1.0
0.07706
CR,COO.NR.
M.O.
1.0
0.01703
NH,
Pp.
0.5
0.04201
0.05 a
5
M.R.
M.R.
0.02 0.001514
1.0 0.02917
1
0.5
M.O.
M.O.
1.0
1.0
0.02016
0.02016
0.5
1
2
M.O.
M.R.
M.O.
1.0
1.0
0.5
0.02016
0.03503
0.04906
2
2
2
1.5
1.5
1
M.O.
M.O.
M.O.
M.O.
M.R.
M.R.
0.5
0.5
0.5
0.5
1.0
0.1
0.05254
0.05106
0.04102
0.04301
0.04069
0.004069
car-
bonate ........
Magnesium oxide.
Magnesium oxide,
heavy .........
Methenamine .. . ,
Potassium acetate
Potassium and so-
dium tartrate ..
Potassium citrate.
Sodium acetate .. .
N.F.
..
= 1.7 to 2.1
10
25
ace-
tate, solution of
= 6.5 to 7.5 W IV
= 30-32
NaHCO, = 23 to 27
C,H,(NO,)' = 87.5 to 112.5'
Mg(OH), = 7 to 8.5
MgO = 39.2 to 41.5
MgO = 96
MgO = 96
(CH,),N. = 99
CR,COOK = 99
KNaC.H.O, = 99
K,C.H,O,.H,O = 99
CH,COON" = 99
Na,C,H,O, = 99
ZnO = 99
ZnO = 13 - 15.5
Ammonium bro-
mide in tablets
of three bro-
= 30.8 to
0.6
M.R.
0.5
0.04898
NH.Br
..
1.5
M.R.
0.5
0.05955
C.H.COONH. = 62 to 67
pared .......
Iron and ammon~
ium
acetate.
solution of. ....
Ichthammol (for
NR,) .......
Lithium carbo~~
ate ............
Lithium citrate ...
Methenamine,
ampuls of ......
Methenamine,
tablets of. .....
Methenamine and
sodium biphosphate, tablets
of .............
Zinc oxide in mild
resorcinol paste
Zinc oxide in
strong
resorcinol paste ..
1.5
M.O.
1.0
0.04069
ZnO
25
M.R.
0.5
M.R.
0.5
1.5
2
M.O.
M.O.
1.0
0.5
= 0.6 to 0.8W IV
= 2.5
0.03694 Li,CO, = 99
0.03498
C,H . OH.(COOLJla
M.R.
1.0
0.03503
(CR,),N.
M.R.
1.0
0.03503
(CH,),H.
mides ...... ,.
Ammonium valer-
ate, acid
Calamin.~.
Iwe-
35.8'
= 98
0.008515 NH.
0.008515 NR,
= 95
= 94
= 98.5
to 105'
to 106'
\"
= 92.5 to
= 24 to 26
0.25
M.R.
0.5
0.01752
(CH,),N.
M.O.
1.0
0.04069
ZnO
M.O.
1.0
o 04069
ZnO = 19 to 21
methyl red.
Pp.
phenolphthalein .
107.5'
104
CHAPTER VI
ACIDIMETRY
106
+H 0
2
Exercise 24
107
ACIDIMETRY
+ 2NaOH--tNa S04 + 2H 0
2
2(40.00)
Exercise 26
108
+ NaOH-NaH BO a + H 0
1 cc. N NaOH =
~10~~
,
= 0.06184
109
ACIDIMETRY
+ NaOH~CaH40HCOONa + H 0
2
160.04
1. Write equations for the reactions that occur in this assay using structural formulae.
2. Ascertain the solubilities of salicylic acid in water and in ether. Explain
why the acid partitions itself largely into the ether layer.
3. What amounts of sodium salicylate might tablets labeled "5 grain
tablets of sodium salicylate" contain and meet the official tolerance
allowances?
110'
+ 2NaOH---Na2C4H406 + 2H 0
2
'Ill
ACIDIMETRY
H 2S0 4
Questions and Problems
1. Why is methyl orange used in place of phenolphthalein in this assay?
112
oooo~o~ooooooooo~~~oooooo
~~~~o~o~~~~~~~~~ooo~~~~~~
ooo~~ooooooooooo~o~oooooo
~~~~o~~~~o~~~~~oo~o~o~~~~
cq
~
.....
1""'1
113
ACIDIMETRY
&<3.
;:::~
.s.
....
"''''
II II
~~
00
00
00
00
iii'S
88
~~
00
.....t~(O~
...-I
1""'4
a;llCc:v:I~I""'i"'d400
COlt:lQOOOO""lf400
..... ...-IC'-IcqOO....-l~'I""'I
0 0 0 0 ..... 0
..... 0
00000000
.....
00000
........
........
... 0
g~
~g
.......
00
00
00
00
00
;o..~
~~
~~
z'S
..... I""'iP"'ll"""4d
.... O,....4
0000""';0"';0
---------7~--------------------------------~~
1.r,)lt:)lt:)COOOOl
oooOcO"';c-io
. 0. . .
It:)
It:)
00
0",
OLQOO",,",
'"
00
II
.""
a'"
.S
:"g
:o;S"
: .~
s
:~
"'"
114
C 6H 4 .OCOCH a.COOH
+ HOH--+C 6H 4 .OH.COOIi +
CHaCOOH
+ NaOH~06H4.000CH3CO(j)Na +
HOH
Amount
used,
Gm. or
cc .
Substance
U.S.P.
Acid, acetylsalicylic
Acid, lactic ........
Acid, sulfuric aromatic ...........
Chloral hydrate ...
Formaldehyde,
solution ....... .
Methyl salicylate ..
N.F.
Acetylsalicylic acid,
tablets of. ......
Ethyl acetate .....
Indicator
I
Official requirement, per cent
--- - _ -
1.5
2.5
Pp.
Pp.
0.5
1.0
0.04502
0.09005
C.H.O(CH,CO)COOH = 99.5
CH,CHOHCOOH = 8S,to 90
S.O
4.0
M.O.
Pp.
1.0
1.0
0.04904
0.1654
H,SO. = 19 to 21 W IV
CChCHO.H,O = 99.5
3.0
2
B.T.B.
Pp.
1.0
0.5
0.03002
0.07603
HCHO = 37
C.H . OH.CO,CH, = 98
O.;7a
Pp.
0.1
0.01801
I.S
Pp.
0.5
0.04403
Pp.
0.1
0.004602 HCOOH
of. ..
.. ,
"
10
methyl orange.
l'p.
0.95 to 1.0SWIV
phenolphthalein
115
ACIDIMETRY
bath for 15 minUtes, with intermittent stirring, allow the solution to stand
at room temperatu~e for 5 minutes, and then titrate with tenth-normal
sulfuric acid. Subtract the number of cubic centimeters of tenth-normal
sulfuric acid used, frOm the total number of cubic centimeters of alkali
added the second time, and multiply the result by 0.01801. This result
represents the weight of acetylsalicylic acid present in the portion of the
pow.der used for the a~say."
+ NaOH~C6H4.0H.COONa +
CH3 COONa
+ HOR
CHAPTER VII
PRECIPITATION METHbD~
Under Neutralization Methods, a class of re~ctions was considered which were of value in quantitative analysis because little
ionized substances or gases or both little ionized substances and
gases were formed. In the following exercises, a cla;;s of reactions
is dealt with which requires the formation of very slightly
soluble substances to cause the reactions to go to sufficient completion to be quantitative in nature. The solubility product
principle may be applied to all precipitation reactions, and it
should be reviewed before the subsequent assays are undertaken.
Determination of the End Point.-The end point of a reaction
in analyses by precipitation methods may be determined in one
of three ways:
1. By adding a standard solution to a solution of the substance
being analyzed until no further precipitate is prbduced. This
method is sometimes applied in the determination of the chloride
ion content of chlorides with standard solution of silver nitrate.
2. By adding the standard solution to a clear solution of the
substance being analyzed until a precipitate begins to form:
This method is often used in the titration of alkali cyanides with
standard silver nitrate solution. (See sodium cyanide reagent,
U.S.P. and diluted hydrocyanic acid, N.F.)
3. By means of a suitable indicator. All of the official assays
by precipitation methods employ indicator solutions to show the
end point of the reaction.
Indicators.-The indicators used in the official volumetric
precipitation assays are:
1. Ferric ammonium sUlfate T.S. prepared by dissolving 8
Gm. of reagent ferric ammonium sulfate in sufficient distilled
water to make 100 cc. This indicator is used in both direct and
residual tit rations of silver and mercury salts with standard
ammonium thiocyanate solution. The thiocyanate reacts with
116
PRECIPITATION METHODS
117
118
PRECIPITATION METHODS
119
Compounds of silver and mercury which can be readily converted into silver nitrate and mercuric nitrate, respectively,
may be estimated by direct titration with standard potassium
thiocyanate soluti6n, using ferric ammonium sulfate as indicator.
The method is based on the quantitative precipitation of the
corresponding thiocyanate, e.g.:
120
and
When all of the metallic ion has been precipitated as thiocyanate, the NH 4SCN reacts with the ferric alum indicator to
form red-colored ferric thiocyanate, marking the end point of
titration:
Ag
2HNO a----+AgNO a
H 20
N0 2
Ag 20
2HNO a----+2AgNO a H 20 .
2. "Filter into a flask, wash the insoluble residue thoroughly with distilled water, cool, and dilute with distilled water, if necessary, to about
75 cc. Add 2 cc. of ferric ammonium sulfate T.S., and titrate with tenthnormal ammonium thiocyanate Each cubic centimeter of tenth-normal
ammonium thiocyanate is equivalent to 0.01079 Gm. of silver."
PRECIPITATION METHODS
121
AgNO a NH 4SCN--AgSCN
NH 4 NO a
169.89
Each cubic centimeter of 0.1 N NH 4SCN is equivalent to
107.88
10 X 1000 = 0.01079 Gm. Ag. The U.S.P. requires that strong
silver protein contain 7.5 to 8.5 per cent silver. Calyulate the
percentage of silver in the sample analyzed and compare your
result with the U.S.P. requirement.
Questions and Problems
1. How does the solubility product principle apply in the above assay?
2. If each cubic centimeter of a solution of NH,SCN is known to be
TABLE XIl.-OFFICIAL SUBSTANCES ASSAYED BY DIRECT TITRATION WITH
0.1 N NH,SCN
Substance
0.01003
0.01083
0.01003
0.01003
0.01083
0.01003
0.01003
0.01003
0.01003
0.01699
0,01699
0.01079
0.01079
Hg = 32 to 34
HgO = 99.5
Hg = 54 to 59.5
Hg = 49.5 to 51
HgO = 24 to 26
Hg = 99.5
Hg = 37 to 39
Hg = 29 to 31
Hg = 49 to 51
AgNO. = 99.8
AgNO. = 94.5
Ag = 19 to 25
Ag = 7.5 to 8.5
0.02272
0.01083
0.01003
0.01003
U.S.P.
Mass of mercury. . . . . . . .. . .. .
Mercuric oxide, yellow ........ .
Mercuric salicylate ........... .
Mercuric succinimide ....... .
Mercury, oleate of. . . . . . . . .. ..
Mercury., ..... , ..... , ..... " ..
Mercury with chalk ... , , ... , . , .
Ointment, mercurial, mild .. , . , .
Ointment, mercurial, strong, ...
Silver ni-trate .... , .. , ..... , .. ,
Silver nitrate, toughened, .. , ...
Silver protein, mild. , ... , . , , .. ,
Silver protein, strong ... , .. , ...
0.5
0.5
0.5
0.5
0.75
0.4
1.0
1.0
1.0
0.8
0.8
1.0
2.0
N.F.
Arsenic and merouric iodides,.
solution of (for HgI 2 ) . 25
Mercuric oxide, red. . ..... , ...
0,5
Mercuric salicylate, ampules of
0.5 a
Mercuric succinimide, ampuls of I 0.25"
122
equivalent to 0.01140 Gm. of pure Ag, what would be its equivalent of Hg,
HgI HgO, Hg(NO.) AgNO., and Ag.O?
3. Give a method for the assay of metallic mercury. Explain each step
in the procedure and write equations for all reactions.
4. What must be the normality of a solution of NH 4SON so that each
cubic centimeter shall be equivalent to 1 mg. of silver?
o. Write equations for the reactions that occur in the assay of: (a) yellow
mercuric oxide, (b) mercuric succinimide, (c) mercuric iodide in solution of
arsenic and mercuric iodides.
RESIDUAL TITRATION METHOD (VOLHARD'S METHOD)
PRECIPlTATION METHODS
123
+ NH4SCN~AgSCN + NH4Cl
+ AgNOa~AgCl + NaNO a
AgNO a + NH4SCN~AgSCN + NH4NOa
NaCl
58.45
10 X 1000
124
3. How might all of the excess silver nitrate solution be freed from the
precipitate and titrated?
4. Name several official chlorides assayed by the above method.
6. What must be the normality of a standard silver nitrate solution so
that each cubic centimeter will be equivalent to 1 mg. of chlorine?
Exercise 34
The above assay is similar to that for chlorides, except that the
precipitated silver bromide need not be removed by filtration,
since it is less soluble than silver thiocyanate. I
The reactions and calculations are similar to those of the preceding assay. Write equations for all reactions involved and
calculate the per cent purity of the ammonium bromide.
Questions and Problems
1. How does the presence of excess silver nitrate tend to produce quantitative precipitation of silver bromide?
2. How does the formation of insoiuble silver bromide force the reaction
to completion?
3. Why may the residual titration of excess silver nitrate be conducted
without removal 0{ the precipitated silver bromide?
4. Look up the solubility product of AgBr and calculate the solubility of
silver bromide.
5. Write all equations ionically.
Exercise 35
PRECIPITATION METHODS
125
Object.-Assay of Elixir
of Three Bromides ..
126
where
0.010291
+ 0.Oll901 + 0.009796
237.8
= --O;:8=0----;:8:-;:;:0----c5;;ro;------;2::;-;;5;-:-x:-:0;:-.8:::-4-;---8~X-:--;:-0.-==85.
0.011902
+ 0.010292 + 0.009796 +
0.009996
+ 0.008686
= 0.01058
PRECIPITATION METHODS
127
0.1 N AgNO.
Amount
used.
Gm.
or co.
Substance
U.S.P.
Acid hydriodic. diluted ...... '.' ..
Acriflavine .................... .
Acriflavine hydrochloride ....... .
Ammonium bromide ....... ... .
Ammonium chloride .... .
Calcium chloride. R ........ .
Chloroform. liniment of. .. . ...
Chloroform. spirit of. . . . . . .
..
Oil of mustard. volatile. .. .. . .
Potassium bromide ............ .
Potassium nitrate .............. .
Sodium bromide ............... .
Sodium chloride ............... .
Syrup of ferrous iodide ......... .
Syrup of hydriodic acid ......... .
N.F.
Ammonium bromide, elixir of
.,
Ammonium chloride. tablets of.
Ammonium iodide ............ .
Bromides, five, elixir of . . , .. - ... .
Bromides, three, elixir of, ....... .
Bromides. three. tablets of. ..... .
Lithium bromide .............. .
Potassium broIuide. elixir of . .... .
Potassi urn chloride . ............ .
Potassium thiocyanate .. , ....... .
Sodium hromide. elixir of. ...... .
Sodium bromide. tablets of ...... .
Sodium chloride in isotonic solution of dextrose and. . ....... .
Sodium chloride in ampuls of dextrose and ................... .
Sodium chloride. ampuls of ...... .
Sodium nitrite. tablets of ....... .
Sodium thiocyanate ... ......... .
R.
a
reagent.
Amount of ingredient Bought.
Per cent of the.labeled amount.
=
WITH
0.1 N NH.SCN
Equivalent of
1 cc. of
0.1 N
NH,SCN
Official requirement,
per cent
_--
5
0.25
0.25
0.4
0.1
2
10
5
4
0.4
0.4
0.4
0.25
10
25
0.01279
0.003546
0.003546
0.009796
0.005350
0.0055.50
0.00398
0.00398
0.004956
0.01190
0.01011
0.01029
0.005845
0.01548
0.01279
HI = 9.5 to 10.5
Cl = 13.3 to 14.3
Cl = 23 to 24.5
NH,Br = 99
NH,CI = 99.5
CaC]' = 74
CHCla = 40 to 45 W /V
CHCla = 8.5 to 9.25 W /V
C,H,NCS = 93
KBr = 99
KNO, .:, 99
NaBr = 99
NaCI = 99.5
FeI, = 6.5 to 7.5W/V
HI = 1.3 to 1.5W/V
10
0.15
0.5
10
10
0.6
0.35
5
0.25
0.2
5
0.3"
0.009796
0.00535
0.01450
0.0102
0.01059
0.007992
0.008686
0.01190
0.007455
0.009716
0.01029
0.01029
NH,Br = 8 to 9W/V
NH,CI = 92.5 to 107.5'
NH,I = 98
total bromides = 25 to 27 W /V
total bromides = 23 to 25 W /V
Br = 70 to 81 b
LiBr = 85 to 90
KBr = 17 to 18W/V
KCI = 99
KSCN = 99
NaBr = 17 to 18W/V
NaBr = 92.5 to 107.5b
0.2"
0.005845 NaCI
0.2
0.2"
0.5"
0.2
0.5
0.5
0.005845
0.005845
0.02070
0.008107
0.01778
0.01596
~
= 0.4 to 0.425W/V
NaCI = 95 to 105 b
NaCI = 95 to 105 b
NaNO, = 91 to 109b
NaSCN = 98.5
SrBro.6H,O = 98
ZnI, = 98
128
CHAPTER VIII
OXIDATION -REDUCTION METHODS
129
130
+ 2HC1~FeCb + H2
(2) Fe
Zero
+ 2H+ +
+ 2( +) +
or
2Cl-~Fe++
2( -) = 2( +)
+ 2Cl- + H2
+ 2( -) + zero.
Fe++----> Fe+++
+ (-)
OXIDATION-REDUCTION METHODS
131
In the reaction
2Fe++
+ Ck-~2Fe+++ + 2Cl-
+ Sn++++
Each ferric ion gains one electron at the expense of the stannous
ions, each of which loses two electrons. The quantity of electricity gained by the iron is 96,500 coulombs for every 55.84 Gm. of
iron reduced, and that lost by the tin is 2 X 96,500 coulombs
for every 118.7 Gm. of tin oxidized. The chloride ion is in the
same state of oxidation before as after the reaction, since it
undergoes no change of charge.
In most cases, the change of charge which an atom, ion, or
radical undergoes in an uxidation-reduction reaction is numerically equal to the change in valence, i.e.:
1. When ferrous iron is oxidized to the ferric condition, the
charge associated with the iron atom changes from two to three:
2Fe++
+ 2H+~2Fe+++ + H2
/
'"
Cl
+ C1 2---2Fe-Cl
Cl
'0>
'"
Cl
+ 5(+)
132
o
---+Mn
/""-/
""-/~
Cl=O
~
----+KCl
OXIDATION-REDUCTION METHODS
133
ion~tetrathionate
--
ion
8 40 6- 2( -) + 2( - )
134
135
OXIDATION-REDUCTION METHODS
~ ~ ;3~9190
~'~~00670
136
+ 8H2S0,--+5Fe2(SO,)3 + 2MnSO,
.
137
OXIDATION.REDUCTION METHODS
138
+ Fe~FeCh + Hg
+ Fe~Fe++ + Hg
2. "Heat the mixture for ten minutes on a water oath, Rhaking it frequently, then- fill the flask to the 100 cc. mark with distilled water, recently
boiled and cooled, and cool the mixture to room temperaturt Again fill
the flask to the mark with distilled water, stopper, agitate the contents well,
and allow to stand for a few minutes."
139
OXIDATION-REDUCTION METHODS
1. Does the iron gain <lr lose electrons when oxidized to the ferrous state
by HgCI.? What quantity of electricity does it gain or lose per mole of Fe?
2. Given pure iron, how might a solution of potassium permanganate be
standardized against it?
3. If the iron in.a 0.15 Gm. sample of iron ore requires 15.0 ce. of 0.1 N
KMnO. for oxidation from Fe++ to Fe+++, what is the percentage of Fe in
the ore?
Exercise 40
The reasons for the various steps in the above assay have
already been given under the assay of ferrous sulfate. This
assay illustrates a case where an oxidizing agent, H 20 2, serves
as a reducing agent for KMn04 and is itself reduced. When
H 20 2 acts as a reducing agCent, 1 Gm.-atom of oxygen from each
mole of H 20 2 is capable of uniting with 1 Gm.-atom of oxygen
from the substance reduced (KMn04.) to form 1 mole of oxygen
gas:
2HO
+0
+O
+ 3H2S04~K2S04 + 2MnS04 + 8H 20
+ 50
140
0.1 N KMnO.
Substance
Amount
used,
Gm. or
ee.
U.S.P.
Ferrous sulfate ..........
Hydrogen peroxide solution ..................
Hydroxylamine hydrochloride, R ...........
Indigo carmine, R, '.' ....
Iron, reduced ...........
Lead peroxide, R ........
Sodium perborate ........
Sodium peroxide, R ......
Equivalent of
1 cc.
0.1 N
KMn04
Official tequirement,
per cent
0.1
0.3
1
0.5
0.25
0.7
0.003475
0.01333
0.005584
0.01196
0.0008
0.0039
NH 20H.HCI = 95
C 16 H,02N 2(S03Na).
Fe = 90
Pb0 2 = 90
Available O 2 = 9
Na20, = 90
.
= 82
R. = reagent.
OXIDATION-REDUCTION METHODS
141
OH 20H(OHOH)4.000 20a.H 20
+ HOI
2CH 20H(OHOH)4_
OOOH + OaOl2 + H 20
448.27
When ammonium oxalate is added to the reaction mixture, the
calcium ion is quantitatively precipitated as oxalate and the
above reaction is forced to the right,
Oa0204
+ H2S04~CaS04 + (OOOH)2.
142
XV.-OFFICIAL
SUBSTANCES
ASSAYED
BY
PRECIPITATION
WITH
0.1 N
KMnO,
Amount Equivaused,
lent of
Substance
Gm. or
ce.
1 ce.
0.1 N
KMnO.
Official
requitement,
per cent
----------
0.4
0.5
0.5
0.009996 CaBr, = 84 to 94
0.002804 C"O = 12.4 to 12.8
0.01091 (CH,CH.OH.COO),Ca = 98
0.6"
0.5a
1.5
OXIDATION-REDUCTION METHODS
143
Procedure.-Dissolve 6.45 Gm. of reagent oxalic acid in sufficient distilled water to measure 1,000 cc. Ascertain its exact strength by titration
against freshly standardized 0.1 N potassium permanganate and adjust to
exacu normality or to a known strength of approximate normality.
144
= normal'lty 0 f am'd
145
OXIDATION-REDUCTION METHODS
5HN0 2
+ 3H 20
1~9.~11,000 = 0.003450
Gm.
1. Why should the tip of the pipette be immersed beneath the surface 0:
the permanganate solution when the solution of sodium nitrite is added?
2. Why is the reaction mixture warmed and allowed to stand?
3. Write ionic ally the reactions involved in the above assay.
4. How much 0.0985 N KMnO. would be required to titrate 0.8544 Gm.
of NaNO. if the NaNO. is 92 per cent pure?
6. Could nitrous acid and other nitrites be assayed by the,above method?
146
+ CO a-H 2CO a
CO 2
+ HiO
147
OXIDATION-REDUCTION METHODS
2. "Transfer this solution to a 200 cc. volumetric flask, add 100 cc. of
tenth-normal oxalic acid, render it alkaline with ammonia T.S., shake the
mixture well, and allow it to stand for three hours at from 60 to 70C., or
over night at room temperature. Cool the liquid if necessary, fill the flask
with distilled water to 200 cc., mix well, filter through a dry filter into a
dry.flask, and reject the first 20 cc. of the filtrate."
The filtrate is transferred quantitatively to a 250 cc. Erlenmeyer flask, acidulated with sulfuric acid and titrated with 0.1
N KMn04 to determine the excess oxalic acid.
The reactions involved are:
1. Solution of CaCO a in HCI:
CaCO a + 2HCI-4CaCI 2
CO 2
+H
148
2. Addition of NH 40H to H 2C 20 4:
H 2C20 4 + 2NH40H~(NH4)2C204
+ 2H 20
(NH4)2C204~CaC204
+ 2NH 4CI
+ H2S04~H2C204 + (NH4)2S0<t.
+ 3H2S04~K2S04 + 2MnS04
+ lOC02 + 8H 0
2
Wt. of sample
X 100
OXIDATION-REDUCTION METHODS
TABLE
149
Amount
used,
Gm.
or cc.
Substance
U.S.P.
Calcium carbonate, precipitated
Calcium chloride ..............
Calcium chloride, fused, R .. ...
Calcium hydroxide .............
Chalk, prepared ...............
Lead acetate ............. .... .
Lead monoxide, R .............
Lime, R ......... ,."."., .. "
N.F.
Calcium chloride, ampuls of .....
0.4
0.3
0.3
0.3
3.5
5
0.4
1
O,25 a
R.
0.1 N
Equivalent of 1
cc. 0.1 N
H 2C 2O.
KMnO.
Official
requirement,
per cent
CaCO. = 98
CaCh = 75 to 85
CaCl. = 94
Ca(OHh = 95
CaCO. = 97
Pb(C.H 3 0.). =
85.31 to 89.57
<;>.0116 PbO = 98
0.002804 CaO = 95
0.005004
0.00555
0.00555
0.003705
0.005004
0.01626
0.007351 CaCI..2H 20 = 95
to 105'
0.01116 PbO = 97
0,01036 Pb = 22.5
0.01036 Pb = 0.7 to
O.8W/V
0.002804 CaO = 95
reagent.
150
+ 3H2S0c-~KCI + 3Fe2(S04)3 + 3H 20
+ 6Fe++ + 6H+
or
= CI-
+ 6Fe+++
OXIDATION-REDUCTION METHODS
151
manganous ions react with permanganate ions to form manganese ions Mn++++. In this state of oxidation, the manganese
is unstable in acid solution, and it is reduced more readily by
ferrous ions than by chloride ions.
3. "Conduct a blank experiment with another portion of 35 cc. of acid
ferrous sulphate. T.S., measured from a burette, and subtract the result
of the former titration from that of the latter. Each cubic centimeter of
tenth-normal potassium permanganate is equivalent to 0.002043 Gm. of
KClO . "
152
+ 2KaFe(CN)6--Fea[Fe(CN)6]2 + 3K S04
2
blue
Exercise 46
OXIDATION-REDUCTION METHODS
153
154
Amount
used
Equivalent of
1 cc.
Official
requirement,
per cent
U.S.P.
Mass of ferrous carbonate .........
1 Gm.
0.01158
3 pills
0.01158
FeCO, = 36 to
41
FeCO, = 0.06
Gm. per pill
2Gm.
0.01158
Substance
N.F.
FeCO, = 15
CHAPTER IX
OXIDATION AND REDUCTION.
METHODS
IODOMETRIC
+ HOH
HI
155
+ HOI
156
or
and
HaAsOa
+ HOI----7H aAs0 + HI
4
+ HCI----7KCI + HI
+ 2HI~2FeCI2 + 12 + 2HCl
or
2Fe+++ + 2I-~2Fe++ + 12
2 X 3( +) + 2( -) = 2 X 2( +)
157
158
+ 2H 2CO a
H 2S 20 a
2NaHCO a + H 2S 20 a
H 2SO a + S
As the sulfurous acid forms, the reducing power of the solution becomes. greater, since 1 mole of the sulfurous acid formed
is equivalent to 2 moles of thiosulfate:
2Na2S20a + 12
2Na1 + Na 2S40S
H 2SOa + 12 + H20~2H1 + H 2S0 4
The sodium carbonate acts as a stabilizing agent by converting
the thiosulfuric acid formed into sodium thiosulfate.
2. "Measure accurately 30 cc. of tenth-normal potassium dichromate
into a glass-stoppered flask and dilute it with 50 cc. of distilled water. Add
2 Gm. of potassium iodide and 5 cc. of hydrochloric acid, stopper and allow
to stand for ten minutes. Dilute with 100 cc. of distilled water and titrate
the liberated iodine with the sodium thiosulfate solution. When the solution has assumed a yellowish-green color, add starch T.S. and continue with
the titration to the discharge of the blue color. Calculate the normality of
the sodium thiosulfate solution and, if desired, adjust exactly to tenthnormal."
14HCl~2CrCla
+ 8KCl + 7H 20 + 31 2.
6(126.92)
159
160
25C. From the weight of the iodine used calculate the normality.
normality of the solution should frequently be redetermined."
The
K1
+ 12
KIa
In the presence of reducing agents, the reaction proceeds quantitatively to the left, and the solution reacts like a solution of
iodine alone.
The iodine should be weighed accurately in a glass-stoppered
weighing bottle, transferred quantitatively to the solution of
36 Gm. of KI in 100 cc. of distilled water, and after it is completely dissolved, the soll!tion should be made up to exactly
1,000 cc. The solution of potassium iodide used to dissolve
the iodine is of sufficient concentration to dissolve the iodine
rapidly so that no appreciable loss will occur due to volatilization.
If pure reagent iodine is used in preparing this solution, it will be
approximately tenth-normal and need not be standardized. Due,
however, to the difficulty of weighing exact quantities of iodine,
it is usually more convenient to prepare a solution of app~oximate
strength and standardize it against 0.1 N sodium thiosulfate
solution as directed in the following exercise.
Exercise 50
161
then dilute the iodine solution so that 25 cc. will require for decolorization
exactly 25 cc. of the 0.1 N sodium thiosulfate at standard temperature.
+ KI
KCl
+ 12
+ 2Na2S20a
2NaI
+ Na2S406
162
Exercise 51
2Na aAsOa
+ 3)I 20
2NaOH
+I
-NaIO
+ NaI + H
163
~~7:;,000 =
0.004946 Gm. As 2 0 a, or
74.96
164
Amount
Equivaused,
lent of
Gm. or
1 cc.
cc.
Substance
Official requirement,
per cent
--U.S.P.
Antimony and potassium tartrate ....
0.5
Arsenic triiodide .................
0.5
Arsenic trioxide ...
0.2
.......
Arsenous acid, solution .............. 20
Potassium arsenite, solution.
.... 20
Sodium thiosulfate ..... .... ....
0.5
Tryparsamide .........
. . . . . . . . . . 0.2
N.F.
Arsenic and mercuric iod.ide, solution
(for AsI,) ........................ 25
Sodium cacodylate, ampuls ... .......
0.2"
I"
0.01670
0.02278
0.004946
0.004946
0.004946
0.01581
0.003746
K(SbO)C.H.O,.UH,O = 99
AsI, = 99
As,O, = 99.8
As,O, = 0.975 to 1.025W/V
As,O, = 0.975 to 1.025W/V
Na,S,O, = 99
As = 25.1 to 25.5
12
2Na2S203.5H20~Na2S406
2(126.92)
+ 2NaI + 10H20
165
0.1 N Na 2S 20a
Slfbstance
U.S.P.
Iodine ......................
Iodine, compound solution of.
Iodine pentoxide, R ..........
Iodine, tincture of ...........
Iodine, tincture of, mild ......
N.F.
~odine, ampuls of. ...........
Iodine, stronger tincture of ...
Iodic acid, R ................
R.
= reagent.
Amount
Equivaused,
lent of
Gm.
1 cc.
or cc.
Official requirement,
per cent
12 =
12 =
1 20.
12 =
12 =
0.5
5.0
0.5
5.0
5.g
0.01269
0.01269
0.002782
0.01269
0.01269
o. 175a
2.0
0.1
99.5
4.5'to 5.5W IV
= 99.5
6.5 to 7.5W IV
1.8 to 2.2W IV
166
2 4
2. "Stopper the flask, allow the mixture to stand with occasional agitation
until complete solution has taken place, and then titrate the residual iodine
with tenth-normal sodium thiosulfate, starch T.S. being used as indicator.
Each cubic centimeter of tenth-normal iodine is equivalent to 0.02361 Gm.
of HgCl."
+ k-~2Hg+t- + 21-
167
Substance
Amount
used,
Gm. or
Equivalent of
1 cc.
CC.
U.S.P.
Acetone ..................
Mercurous chloride ........
Mercurous iodide ..........
Methylthionine chloride ...
Sodium bisulfite, R ........
Sodium sulfite, R ..........
Sulfurous acid, R ..........
l.0
0.7
1.0
0.12
....
0.25
2.0
Official requirement,
per cent
---
0.0009675
0.02361
0.03275
0.005328
0.005203
0.006303
0.003203
CR,COCR, = 99
HgCI = 99.6
HgI = 99
C 16H 1S N 3C1S = 98.5
NaHSO, = 90
Na 2S03 = 95
S02 = 6
N.F.
Mercurous chloride, mild,
and sodium bicarbonate,
tablets of ...............
Mercurous chloride, mild,
tablets of ...............
R.
= reagent .
0.02361
0.3"
168
KI
HCl----+ KCI
HI
2FeCI s
2HI----+2FeCb
162.21
+ 2HCl + 12
or
2Fe+++
+ 2I---+2Fe++ + 12
169
Amount Equivaused,
lent of
Gm. or
1 cc.
cc.
Substance
---------
~---I---
U.S.P.
}'erric
Ferric
Ferric
Ferric
2.0
5.0
1
1.5
1.0
1
OF THE
Official requirement.
per cent
---1-------0.005584
0.005584
0.005584
0.005584
0.005584
0.005584
Fe
Fe
Fe
Fe
Fe
Fe
= 10 to 11
= 4.5
= 16.5 to 18.5
= 9.5 to 10.5
= 16.5 to 18.5
= 14.5 to 16
0.005584
0.005584
0.005584
0.005584
0.005584
0.005584
0.005584
0.005584
Fe = 4.48 W IV
Fe = 17
Fe = 21.8
Fe = 2.8 to 3.2
Fe = 12 to 15
Fe = 10.5 to 12.5
Fe = 20 to 22WIV
Fe = 0.16 to 0.20W/V
N.F.
Ferric citrochloride. tincture of. .... "
5.0
Ferric glycerophosphate .............. .
0.5
Ferric hypophosphite ................. .
1.0
Ferric oxide, saccharated .............. .
8.0
Ferric phosphate, soluble . ............ .
1.0
Ferric pyrophosphate, soluble. . . . .
..
1.0
Ferric subsulfate, solution of ......... .
1.0
Iron. and ammonium acetate, solution of.
25
Iron and ammonium citrates, green,
ampuls of .......................... '" I"
Iron, peptonized. . .. . .......... , .... .
0.5
t
0.005584 Fe
0.005584 Fe
= 14.5 to 16.0b
= 16 to 18
tion of .......................... .
Iron, peptonized. solution of . .......... .
R. = reagent.
" Amount of ingredient sought.
b Per cent of the labeled amount.
25
25
170
Exercise 55
171
+ Ca(OClh
IS
From the above reactions, it is apparent that 2N a 2S20a is equivalent to 12 which is equivalent to Ch
One cubic centimeter of 0.1 N Na 2S20a is equivalent to
10 1~6i~~00 = 0.012692 Gm. iodine and 10 ~i~oo = 0.003546
Gm. chlorine.
Other substances which yield free chlorine or free bromine
when treated with acids may be assayed in the same way, e.g.,
solution of sodium hypochlorite.
Questions and Problems
1. What is "available chlorine"?
2. What function does KI serve in"this assay? Must the KI be present
in excess?
3. If a 0.4 .Gm. sample is known to contain 32 per cent of available
chlorine, how much KI would be necessary to yield an amount of iodine
equivalent to the chlorine?
4. Look up the U.S.P. requirement for chlorinated lime and compare it
with the assay result.
172
Amount
Equivaused,
lent of
Gm. or
1 cc.
cc.
Substance
U.S.P.
Chloramine-T ..........
Dichloramine-T ........
Chlorinated lime, R .....
Sodium hypochlorite,
solution of ...........
Sodium hypochlorite,
solution of, diluted ...
0.1 N Na 2S20.
Official requirement,
per cent
0.2
0.1
4
0.003723 NaOCI = 4 to 6
25
R. = reagent.
Exercise 56
+ 2K2S0 + 12
4
+ 4I-~2Cu+ + 21- + 12
173
U.S.P. copper sulfate should contain not less than 63 per cent
or more than 66.8 per cent .of CUS04 corresponding to 98.5
per cent of CuS04.5H20. Calculate the per cent Cu, CUS04
and CuS04.5H 20 in the sample assayed.
Questions and Problems
1. What function does the acetic acid serve in this assay?
2. Explain the reduction of copper from the cupric to the cuprous condition in accordance with the ionic theory. Indicate all transfers of charge.
3. How much iodine will 0.25 Gm. of CUS04 liberate from KI in acid
solution?
Exercise 57
"
174
. 1
185.91
1 cc. o
f 0
. 1 N N a2S 2O3 IS eqmva ent to 2 X 10 X 1,000
0.009295 Gm. Na2HAs04.
N.F. exsiccated sodium arsenate contains not less than 98
per cent of Na 2HAs0 4 Calculate the per cent purity of the
sample assayed and compare the result with the official requirement. Also calculate the per cent of arsenic in the sample
assayed.
Arsenic and antimonic compounds may be assayed by methods
similar to that given above. The arsenic and antimony present
in organic compounds in the trivalent state may also be assayed
by this method after quantitative oxidation to the pentavalent
state. Such procedure is employed in the official assays of
arsphenamine and neoarsphenamine.
Questions and Problems
1. Assuming that the sample used in the assay was pure Na.HAsO . 7H.O,
how much KI would be required?
_..2. Write the equations involving oxidation-reduction ionically.
3. Name several official arsenic and antimonic compoundi assayed by
methods which employ the same basic principles.
4. What change in valence does the arsenic undergo in the above assay?
Does the change of valence correspond with the change of charge?
TABLE
X 4 III.-OFFICIAL
Substance
Amount
Equivaused,
lent of
Gm. or
1 cc.
cc.
KI
WITH
0.1 N Na 2S20.
Official requirement,
per cent
-U.S.P.
Arsphenamine .....
Neoarsphenamine ..
N.F.
Sodium arsenate,
exsiccated .......
Sodium arse'nate,
solution of. ......
0.2
0.2
0.003746 'As = 30
0.003746 As = 19 to 22
0.3
0.009295 Na 2HAsO. = 98
25
175
Exercise 68
Object.-Assay of Thyroid.
Materials Required.-1 Gm. of thyroid.
A nickel crucible.
9 Gm. of anhydro-qs potassium carbona,te.
7 Gm. of anhydrous sodium carbonate.
5 Gm. of potassium nitrate.
50 cc. of solution of chlorinated soda.
About 60 cc. of diluted phosphoric acid (1 to 1).
0.1 Gm. of potassium iodide.
0.005 N sodium thiosulfate.
Starch indicator solution.
Procedure.-l. "Thoroughly mix 1 Gm. of Thyroid, finely powdered and
accurately weighed, with 15 Gm. of an intimate mixture of 138 parts by
weight of anhydrous potassium carbonate, 106 parts of anhydrous sodium
carbonate arid 75 parts of powdered potassium nitrate in a nickel crucible
of about 125-cc. capacity, and spread an additional 5 Gm. of this mixture
evenly over the surface. Heat the crucible with the flame of a Bunsen
burner at such a rate as to attain a dull red color in ten minutes, and continue
the heating at the same temperature for an additional ten-minute period.
At the end of this time the carbonaceous material is completely oxidized
and the mixture has just begun to melt around the wall of the crucible.
Cool the fusion mixture and place the crucible and contents in a 400-cc.
beaker. Add 150 cc. of hot distilled water and stir until the contents of the
crucible are completely dissolved."
2RI + K2C03~2KI + CO 2 + H 20
KI + 3KN03~KI03 + 3KN0 2
In the above reactions it is assumed that all of the oxygen set
free when potassium nitrate is heated is not utilized in the oxida-
176
tion of the organic matter present but that some of it reacts with
KI to form KIO g After carbonization is complete and the
crucible has cooled, the residue is treated with distilled water
which dissolves the iodide, iodate, carbonates, and nitrite.
2. "Transfer the solution to a 500-cc. Erlenmeyer flask and rinse the
beaker and crucible with four, lO-cc. portions of hot distilled water, adding
the rinsings to the solution in the flask. Cool the solution to 15C. and
add 50 cc. of freshly prepared chlorinated soda T.S. Cautiously add 60 cc.
of dilute phosphoric acid (made by mixing equal volumes of phosphoric acid
and distilled water), place the flask on a hot plate and boil the solution until
a strip of filter paper, moistened with starch-potassium iodide T.S., does not
become blue when held in the vapor in the mouth of the flask. The final
volume of solution in the flask must be about 175 cc., and distilled water
must be added, if necessary, during the boiling to maintain this volume."
+ 2HOCI
177
2Kl
oHl
+ H P0 K HP0 + 2Hl
+ K10a~Kl + 3H20 + 31
3
N Na 2S 20a is equivalent to 6 X
i02;.~21,000
0.0001058 Gm.
Substance
KI
WITH STANDARD
Na 2S 20.
Amount
EquivaNorused,
malityof lent of
Gm. or
1 cc.
Na 2S20.
cc.
U.S.P.
Calcium iodobehenate ..
Thymol iodide .........
Thyroid ...............
Thyroxin ..............
0.5
0.25
1.0
0.02
0.1
0.1
0.005
0.005
0.002115
0.002115
0.0001058
0.0001058
12 = 23.5
12 = 43
12 = 0.17 to 0.23
12 = 64
178
179
Substance
U.S.P.
Amyl nitrite ............
Ethyl nitrite, spirit of ....
Glyceryl trinitratc, spirit
of. .. '................
EquivaAmount lent of
used,
1 cc. of
0.1 N
Gm.
Na,S,O.
Official requirement,
per cent
3.5
10
0.01171 C.HuONO = SO
0.007505 C 2H.ONO = 3.5 to 4.5
25
0.0113
C.H.(ONO,).
= 1 to 1.1
Substance
Amount
used,
Gm. or
cc.
U.S.P.
Chromium trioxide ..........
Cupric sulfate ...............
Potassium bromate, R .......
R.
reagent.
1
1
0.3
Equivalent of
1 cc. of
0.1 N
Official requirement,
per cent
Na,S 2O.
0.003334 CrO, = 95
0.01596 CUS04 = 63 to 66.S
0.002784 KBrO. = 99.S
180
In the assay of compounds such as aniline, phenol, and resorcinol, bromine is employed as an oxidizing agent in place of iodine
since it forms tribrom derivatives quantitatively which are
insoluble in water in the presence of bromine in slight excess.
The volumetric solution does not contain bromine as such, but
it contains potassium bromide and potassium bromate. Mixtures of these salts in solution liberate bromine when treated with
an acid.
Exercise 60
When the solution of potassium bromide and potassium bromate is acidulated with hydrochloric acid, bromine is set free:
5KBr
+ Br2~2KBr + 12
+ 2Na2S208~2Nal + Na22406
181
~o 0.1 =
0.1250 normal.
Each
Object.-Assay of Phenol.
Materials Required.-1.5 Gm. of phenol.
30 cc. of 0.1 N bromine solution.
1 Gm. of potassium iodide.
1 cc. of chloroform.
0.1 N sodium thiosulfate.
Starch indicator solution.
Procedure.-l. Dissolve about 1.5 Gm. of phenol, accurately weighed,
in sufficient distilled water to make 1,000 cc. Transfer an aliquot portion of
this solution, containing from 0.038 to 0.041 Gm. of phenol, to a 500 cc.
glass-stoppered flask having a long, narrow neck, add 30 cc. of 0.1 N bromine, then 5 cc. of hydrochloric acid', and immediately insert the stopper.
Shake the flask repeatedly during :hi hr., allow it to stand for 15 min.,
remove the stopper just sufficiently to introduce quickly 5 ce. of an aqueous
solution of potassium iodide (1 in 5), being careful that no bromine vapor
escapes, and at once stopper the flask.
+ 3Br2~CsH2Br30H + 3HBr
182
Na2S203~2Na1
+.Na2S406
C 6H 50H.
Liquefied phenol and resorcinol are assayed by the same
method. Acetanilid in tablets of acetanilid is determined by a
special method which is based upon the formation of tribromaniline during direct t~tration with a standard bromine solution.
Questions and Problems
183
+ H2S04~(NH4hS04 + 2HPH 20 2
2(83.07)
H
/
HO-P=O
'"
HO
'"
+ 2Br2 + 2H20~HO-P
66.04
4(79.916)
+ 4HBr
HO/
98.04
184
18;~71,000
0.1 N
Substance
U.S.P.
Phenol .......... '" ..
Phenol, liquefied .......
Phenol ointment .......
Resorcinol. ...........
Amount
used,
grams
0.1 N
BROMINE
Equivalent of
1 CC.
0.1 N
bromine
1.5
1.5
2
1.5
0.001568
0.001568
0.001568
0.001834
0.12
0.12
0.12
0.12
0.002604 KPH20. = 98
1
0.12
0.001834 C.H.(OH)z = 19 to 21
0.002651 NaPH.O . H 20 = 98
0.002668 C 6H . OH.COONa
C6H sOH =
C6H,OH =
C.H,OH =
C.H.(OH)2
98
88
1.8 to 2.2
= 99.5
N.F.
= 48 to 52
185
186
+ KIO a + 6HCI--).6KCI + 31 2 + 3H 20
When sufficient HCI is present in the reaction mixture, the equation representing the reaction is:
2K1 + KIO a
2(166.02)
+ 6HCl-3KCI + 31Cl + 3H 2 0
+ 15+-31+
2(-)+5(+) =3(+)
Each atom of iodine combined as iodide loses 2 electrons and each
atom of iodine combined as iodate loses 4 electrons. Each cc. of
0.05 M potassium iodate is equivalent, therefore, to 2~(~6i~~~0
187
Amount
Substance
used,
Om. or
cc.
Equiva-
Molarity
lent of
of KIO.
1 cc.
KIO
Official requirement,
per cent
--U.S.P.
0,3
0.3
0.35
0.5
0.5
0.05
0.05
0.05
0.05
0.05
0.060.2
0.13-
0.02
0.05
",0.02
O.la
0.02
0.05
0.02
0.05
0,01269
0.01269
0.01269
0.01660
0.01499
I = 26.5 to 28.9
I = 61 to 62
I = 39 to 41
KI = 99
NaI = 99
N.F.
5
O.la
0.5"
HgI = 91 to 109'
KI = 97 to 103W/Y
KI = 92.5 to 107.5'
NaI = 92 to 105'
CHAPTER X
GASOMETRIC METHODS
The assay processes which involve the volumetric measurement of gases are of two types, namely:
1. The purity of a gas is determined by absorbing one of the
components of a gaseous mixture by means of a suitable absorbing
agent and measuring the quantity of gas absorbed by the change
in volume.
2. The purity of a given substance is determined by measuring
the quantity of gas which it may be made to evolve in a given
chemical reaction.
Theory.-According to the kinetic theory of gases, the molecules of a gas are in constant motion. When a gas is enclosed in a
vessel, it exerts a definite pressure due to the combined effects of
the impacts of the moving molecules of gas upon the walls of
the containing vessel. The magnitude of the pressurE\ exerted
depends on the number of molecules which strike a given surface
in a given period of time. The number of molecules which strike
upon the surface in a given period of time is dependent upon the
number of molecules present and upon the velocity of the molecules. The velocity of the molecules varies with the temperature
of the gas; the higher the temperature the greater the velocity of
the molecules, and the lower the temperature the less the velocity
of the molecules. If the temperature and pressure of a gas remain
constant, the volume of the gas will depend on the number of
molecules present.
The official gasometric determinations pertain only to substances which behave as "perfect" gases, that is, gases in which
there is no dissociation or association of the molecules, and which,
therefore, obey the gas laws. Consequently, a definite volume
of such a gas measured under laboratory conditions at a known
temperature and pressure provides the data required to calculate
the weight or volume of the gas present under standard condi188
GASOMETRIC METHODS
189
tions, 'as will be shown subsequently. The term standard conditions is used to designa:te a temperature of 00. and a pressure
equal to that exerted by a column of mercury 760 mm. in height.
Whenever the volume of a gas is given, it is understood that the
gas occupies the specific volume when measured at 00. and
at a barometric pressure of 760 mm. unless otherwise stated.
Standard conditions should not be confused with the expression
normal conditions which has reference to the measurement of
gases at 250. and 760 mm. pressure.
It has been found by experiment that 22.4: l. of oxygen measured at 00. under a pressure of 760 mm. weighs 32 Gm. and that
the same volume of hydrogen measured under standard conditions
weighs 2.016 Gm. These facts are embodied in Avogadro's
hypothesis, which is: Equal volumes of gases measured under the
same conditions of temperature and pressure contain the same
number of molecules. In the case of perfect gases, this hypothesis
may be stated: Equivalent molecular weights of gases confined
under identical conditions of temperature and pressure occupy the
same volume. Thus, 2.016 Gm. of hydrogen, 32 Gm. of oxygen,
30.01 Gm. of nitric oxide, or 14:.008 Gm. of nitrogen will occupy
22.4: l. when measured at 00. and 760 mm. pressure. According
to Boyle's law: The volume of a gas is inversely proportional to
the pressure upon it if the temperature remains constant. Doubling
of the pressure would diminish the volume one-half, and, conversely, diminishing the pressure one-half would double the
volume. Th,e product of the pressure and volume is therefore
constant. Boyle's law may be stated in algebraic form as follows:
or
VI = P 2 = K
V 2 PI
where PI and VI are the pressure and vollfme under one set of
conditions and P 2 and V 2 are the pressure and volume under
another set of conditions, K being their constant product. The
magnitude of K depends upon the quantity of gas measured. If
PI and VI are used to represent the observed pressure and volume
of a gas, respectively, and P 2 is standard pressure (760 mm.),
the volume V 2 which the gas will occupy at P 2 may be calculated;
e.g., if a sample of gas measured at 25C. and 750 mm. pressure
occupies a volume of 50 cc., what volume will it occupy at 25C.
190
and
VI =
50 X 750
760
= 49.35 cc.
+i
+ t2
and
V _ V 2 X 273
I 273
t2
tl
or I
273 + 25
273 + 0
and
V2
_ 50 X 273
298
= 45.81 cc.
V - P 2V 2T 1
1 -
P 1T 2
GASOMETRIC METHODS
191
FIG. 15.-Gas
burette with level
ling flask. (Cour.
tesy Fisher Scienti
fie Company.)
192
193
GASOMETRIC METHODS
Substance
U.S.P.
Carbon dioxide .. ....
Ethylene ............
Nitrogen monoxide ..
Oxygen .............
Absorption reagent
Potassium hydroxide
Bromine
Water
Copper with NH.CI and
NH 40H
CO. = 99
CH. = CH 2 = 99
N 20 = 95
0=99
194
GASOMETRIC METHODS
195
196
C 2H 5N0 2
+ H20~C2H50H + HN0 2
HN0 2 +
KHC03~ KN0 2
+ H 20 + <\)0 2
GASOMETRIC METHODS
197
KI
+ H2S0r--~KHS04 + HI
and the liberated hydriodic acid reacts with the ethyl nitrite in
the spirit, setting nitric oxide gas free:
20 2H 5N0 2 +
2HI~202H60H
+ 12 + 2NO
2KI
+ 202H
N02 + H2S04~202H50H
+ 12 + 2NO + K 2S0 4
198
2732~ 25
1.2281 Gm., and each cubic centimeter of nitric oxide gas will
contain 0.0012281 Gm. of NO.
The volume of gas being known and the temperature in degrees
centigrade and the barometric pressure in the laboratory having
been ascertained, the weight of nitric oxide gas evolved by a
given weight of spirit of ethyl nitrite may be calculated; e.g., an
aliquot portion of an alcoholic solution of spirit of ethyl nitrite
equivalent to 4.0 Gm. of the spirit when assayed evolved 50 cc.
of nitric oxide measured at 21C. and 740 mm. pressure. What
percentage by weight of ethyl nitrite did the sample contain?
Substituting in the algebraic equation which expresses the combined laws of Boyle and Charles,
2V 2 T t
we obtal'n V = 740 X 50 X 298 = 4935
V t = PPlTl
1
760 X 294
. cc.,
the volume corrected to 25C. and 760 mm. pressure. 49.35 X
0.0012281 = 0.06061 Gm. NO contained in 49.35 cc., at 25C.
and 760 mm. pressure.
~
Since 1 mole, 75.05 Gm., of ethyl nitrite, C 2H oN0 2, evolves 1
mole, 30.01 Gm., of nitric oxide, NO, each gram nitric oxide is
the approximate equivalent of 75/30 = 2.5 Gm. ethyl nitrite,
and 0.06061 Gm. of NO is equivalent to 0.06061 X 2.5 = 0.1515
Gm. C 2H oN0 2
The percentage by weight of ethyl nitrite contained in the
.
0.1515 X 100
4.0
= 3.79 per cent. Calculate
sample IS therefore
0,
GASOMETRIC METHODS
199
PART II
PHYSICO-CHEMICAL METHODS USED IN
'OFFICIAL PHARMACEUTICAL ANALYSIS
The anaiysis of many of the official substances for the purpose
of identifying them and of determining their purity or therapeutic value is based on the measurement of certain physical and
chemical characteristics or constants, considered in conjunction
with the estimation of certain special components by assay, and
qualitative tests for various substances commonly present as
i:rb.purities or added for the purpose of adulteration.
The qualitative methods employed in the determination of the
physical characteristics or physical constants of official substances
are frequently applied to materials of widely divergent nature;
e.g., valuable criteria relative to the purity of volatile oils, sugars,
and alkaloids may be gained by the measurement of the optical
activity. The fundamental principles involved in ascertaining
the physical constants of these substances are the same regardless
of the nature of the substance, although slight modifications
of the technique employed are frequently necessary.
The Pharmacopoeia and National Formulary, as a rule, specify
that certain methods and apparatus shall be employed in the
determination of the physical constants of official substances.
In such cases, the methods are known as official methods and the
apparatus as official apparatus.
CHAPTER XI
SOLUBILITY
The statements of the solubilities of official substances are
given primarily jor the information of physicians and pharmacists
for use in the preparation and dispensing of medicines. They
should not always be regarded as exact physical constants upon
which the ideI\tification or the determination of the purity of I:!substance may be based. Frequently, the official standards are
descriptive telms to indicate the approximate solubility of substances, viz.:;(1) "Very soluble," 1 part of the substance is soluble
in less thao/1 part of the solvent; (2) "freely soluble," 1 part of the
substancft'is soluble in from 1 to 10 parts of solvent; (3) "soluble,"
1 part of the substance is soluble in from 10 to 30 parts of solvent;
(4) "spAringly soluble," 1 part of the substance is soluble in from
30 to )00 parts of solvent; (5) "slightly soluble," 1 part of the
subst~nce is soluble in froVl 100 to 1,000 parts of solvent; (6)
"very slightly soluble," 1 part of the substance is soluble in from
1,00Q to 10,000 parts of solvent; and (7) "practically insoluble,"
mor~ than 10,000 parts of solvent are required to dissolve 1 part
of the substance.
There are nine possible classes of solutions, namely: (1) a gas
in a gas; (2) a gas in a liquid; (3) a gas in a solid; (4) a liquid
in a gas; (5) a liquid in a liquid; (6) a liquid in a solid; (7) a
solid in a gas; (8) a solid in a liquid; and (9) a solid in a solid.
Although examples of all of these different types of solutions
are known, the only classes of pharmaceutical importance are
solutions of gases in liquids, olliquids in liquids, and of solids
in liquids.
The official determination of the solubility of gases in water,
such as HCI and NH a, is generally effected by chemical titration
methods, while the solubility of liquids in liquids and of solids
in liquids is determined by physical methods.
203
204
Numerous factors affect the rate and the extent of the solubility of a substance in a given solvent as follows:
1. The solubility of most of the official substances is increased
by a rise in the temperature at which solution is effected. There
are numerous exceptions to this generality, however; e.g., gases,
calcium salts; and ether are less soluble in hot thah in cold water.
Since the solubility of substances varies marketlly with slight
changes in temperature, it is very important that a constant
temperature be accurately maintained throughout a solubility
determination.
2. Substances in a fine state of division dissolve more rapidly
than large crystals or particles because the tot!)'l surface area
exposed to the action lof the solvent
is much greater when. the substance
is powdered.
3. The purity of the ~ubstance and
of the solvent must be assured in all
solubility determinations, since slight
amounts of impurity in either may
cause considerable- variation in the
results. In the official state~ents of
solubility, it is assumed that both the
substance and the solvent employed
conform to the official tests for purity.
4. The position of the solute in the
solvent affects the rate of solution.
If the solute is allowed to lie on, the
FIG. IS.-Apparatus for solubility determinations. A As- bottom of the vessel, it becomes
sembled apparatus. B Stirrer. surrounded by a layer of concentrated
solution which prevents the access of fresh portions of the solvent
to the surface of the solute.
The determination of the solubility of a solid in a liquid necessitates the preparation of a saturated solution. The prod.uction
of a saturated solution of this type may be carried out in the
apparatus illustrated in Fig. 18. This apparatus consists of a
hard-glass test tube A of medium size into wh~ch the solvent and
solute are placed and stirred vigorously by means of a motordriven glass screw stirrer B. The stem of the stirrer passes
through a glass tube, inserted through a well-cleaned stopper by
SOLUBILITY
205
The weight of the boric acid contained in the residue, subtracted from the weight of the solution analyzed, gives the weight
of the "\Vater in which the boric acid was dissolved.
3. Attach the stirrer, and allow the stirring to continue for about one
hour. Again remove. a 5 cc. portion of the solution, weigh it accurately,
206
and determine the amount of boric acid contained in it in the same manner
as before.
0.3:5.2: :X:100
in which X = the number of grams of boric acid ~oluble in 100
Gm. of water at the temperature at which the dEl,termination
was carried out.
Calculate the solubility of boric acid in water at 25C. from the
results of the above determination.
Questions and Problems
1. What factors influence the rate of solution of boric acid in water?
2. Why is the accurate control of temperature throughout a solpbility
determination essential?
3. Consult the table on page 623 of the U.S.P. and express the restlts of
the above determination in terms of grams of boric acid soluble in 100 cc.
of water at 25C., indicating all calculations, if any are necessary.
CHAPTER XII
SPECIFIC GRAVITY AND DENSITY
The absolute density 'of a solid or liquid is the mass of unit
volume of the substance. Generally, however, in using the term
density, the relative density or the density at a given temperature
relative to the density of distilled water, either at the same temperature, represented by d, or at 4C., represented by dfo is
understood. When in the latter case, the density is corrected
for the buoyancy of the air, the number obtained represents the
true specific gravity of the substance. . In common practice, however, and in all except very exact work, the specific gravity of a
substance is taken as the ratio of the weight of the substance to
the weight of an equal volume of distilled water at the same
temperature.
In the official standards, the specific gravity of a substance has
been established as the ratio of the apparent weight of the substance in air at 25C. to that of an equal volume of distilled water
at the same temperature, or d~~~, except when otherwise stated and
in the case of alcohol, which should be determined at 15.56C.
and compared with water at the same temperature. The latter
is the standard temperature established by the U. S. Revenue
Department for the measurement of the specific gravity of alcohol.
A considerable number of methods hav:e been developed by
which the specific gravities of various substances can be determined. Only those methods of practical importance most
commonly used in pharmaceutical analysis, to establish the
identity and purity of medicinal substances, will be considered
in the following pages. These methods may be classified as
follows:
A. Methods used to determine the specific gravity of liquids.
1. By the use of a pycnometer.
2. By the use of the Westphal balance.
207
208
FIG. 20.-Sprengel-Ostwald
pycnometer (modified form).
209
O~~A~
IfPE=B~~
FIG. 21.-Sprengel-Ostwald pycnometer with ground-on glass caps and groundon glass side tube for use in filling.
210
. h one 0 f k nown
y b
companson
WIt
accuracy whenever exact determinations are made.
In ascertaining th,e specific gravity of a liquid with this
pycnometer, the thermometer and cap are removed, the previously cleaned bottle is filled with the liquid which has been
cooled to from 1 to 3C. below the temperature at whicli the
specific gravity is to be determined. The thermometer is then
fitted to the bottle, using due precautions so that no air bubbles
remain in the bottle. The pycnometer with its contents is
warmed to the required temperature, any excess liquid that
exudes from the capillary tube is carefully wiped off, the cap
is fitted to the side tube and the whole is weighed.
211
Exercise 69
To Determine the Alcohol Content of an Official Preparation.It is very difficult to effect a quantitative separation of alcohol
from the solvents ordinarily employed in the manufacture of
pharmaceutical preparations, but it is comparatively easy to
212
213
214
215
216
FIG. 23.-Plummet.
FIG. 25.-Riders.
217
The temperature of the oil (25C.) at which the final adjustment of the balance is made should be the same as that of the
water used to standardize the apparatus. The specific gravity
is read directly from the position of the riders on the beam;
e.g., if the largest rider is at 9, the second at 7, the third at 5,
218
x =
0.85
219
ments in the set of four are calibrated to read from 0.600 to 1.000,
from 1.000 to 1.400, from 1.400 to 1.800, and from 1.800 to 2.200.
When making a specific gravity determination with a hydrometer, the thoroughly cleaned instrument should be allowed to
sink in the liquid gradually until it is at rest, then depressed
about 1 in. to 'moisten a portion of the stem, allowed to come to
equilibrium, and the reading taken.
Exercise 71
~5 X 100
= 57.1430 Gm.
220
221
Since the camphor is lighter than water, the weight of the sinker
and camphor is less than the weight of the sinker alone. The
difference between the weight of the sinker and camphor in water
and the weight of the sinker alone in water plus the weight of the
camphor in air is a measure of the water displaced by the camphor
and also a measure of its buoyant power, e.g.:
Weight of the camphor in air = 4 Gm.
Weight of the sinker in water = 1.6 Gm.
Weight of the camphor and sinker in water
1.5 Gm.
222
The wax globules are moistened with water so that the water:alcohol mixture will come in contact with all portions of the
globules without occluding air at the intersurface. When the
globules are in equilibrium in the alcoholic solution, their weight
must be equal to the weight of liquid which they displace or they
would rise to the top of the liquid and float or sink to the bottom
of the beaker. Consequently, when such equilibrium is attained,
the specific gravity of the wax and that of the liquid are equal,
and a determin.ation of the specific gravity of the liquid is a
measure of the specific gravity of the wax.
3. Solids Heavier than and Soluble in Water.-The specific
gravity of solids heavier than and soluble in water may be determined by weighing the solid in air and then in some liquid of
known specific gravity in which the solid substance is insoluble
such as oil of -turpentine, chloroform, benzene, etc. Thus, the
weight of a piece of alum in air divided by its loss in weight when
223
3.5:X::0.86:1
= 4.070 Gm.,
.
where X is the weight of a volume of water equal to the volume
of the oil of turpentine displaced, and 10/4.070 = 2.4570, the
specific gravity of the alum.
4. Solids Lighter than and Soluble in Water.-The specific
gravity of substances lighter than and soluble in water may be
de~ermined by weighing the substance with a sinker in some
liquid of known specific gravity in which the substance is not
soluble. For example, the specific gravity of lithium may be
determined from the data below as follows:
Weight of the lithium in air = 2.0 Gm.
Weight of the sinker in air = 5.0 Gm.
Specific gravity of the sinker (brass) = 8.4
Specific gravity of liquid (kerosene) = 0.830
Weight of lithium and sinker in kerosene = 3.8 Gm.
The density X of the sinker referred to kerosene as a standard is
0.830:1 ::8.4:X
10.1205
5.05~
Y = 10.1205
Y = 4.5095,
+ 4.5060
- 3.8 = 0.7391.
224
1)..900 Gm.
225
Substance
U.S.P.
Acid, aeatic, glacial. ......
Alcohol (at 15.56C.). , .
Al c oh 01, d eh yd r a ted
(15.56C.) ..............
Alcohol, diluted (15.56C.).
Amyl nitrite............
Balsam, Peruvian .........
Benzin, petroleum, purified
Brandy ..................
Bromine, R.1 .............
Camphor, spirit of ........
Carbon tetrachloride ......
Chloroform ..............
Collodion ................
Copaiba .................
Creosote .................
Creosote carbonate ........
Cresol. . . . . . . . . . . . . . . . . ..
Ether ...................
Ether, absolute, R ........
Ethyl acetate, R ..........
Ethyl nitrite. spirit of. ....
Ethyl oxide ..............
Eucalyptol. ..............
Eugenol. . . . . . . . . . . . . . . ..
Ferric chloride, solution of
Glycerin .................
Giyceryl trinitrate, spirit of
Honey' ..................
Malt, extract of. .........
Methyl salicylate (natural)
Methyl salicylate (synthetic) ....................
Oil (fixed) of
almond, expressed .......
castor .................
chaulmoogra ...........
cod liver ...............
corn ...................
cottonseed .............
linseed .................
olive ....... \ ..........
theobroma' ............
Oil (volatile) of
anise ..................
bitter almond. . . . . . . . ..
chenopodium ...........
cinnamon ..............
clove ..................
coriander ..............
Specific
gravity,
25C.
Substance
U.S.P.
dwarf pine needles ......
eucalyptus .............
!en~el. ................
(n.m.t.) 0.798
Jumper ................
0.935 to 0.937
lavender .............
0 865 to 0.875
lemon .................
1.150 to 1.170
mustard ...............
0.634 to 0.660
myristica ..............
0.933 to 0.921
orange .. : ..............
(n.l.t.) 3.099
peppermmt ............
0.824 to 0.826
rose' .................
1.588 to 1.590
rosemary ..............
1.474 to 1.478
santa!....... ........
0.765 to 0.775
sassafr'!s. . . . .. ........
0.930 to O. 995
spearmmt .. '" ........
(n.l.t.) 1.076
tar, rectified ............
(n.l.t.) 1.145
turpentine .............
1.030 to 1 .038
turpentine, rectified.. ..
0.713toO.716 Oleoresin of aspidium ......
(n.m.t.) 0.710
Ox bile ..................
0.893 to 0.898 Paraffin, chlorinated .......
(n.m.t.) 0.823
Petroleum' ...............
0.713 to 0.716 Pet~olatum,liquid ........
0.921 to 0.923 Rosm...................
1.066 to 1.070 Spermaceti ...............
1. 29 to 1. 32
Sodium hypochlorite, di(n.l.t.) 1.249
luted solution of ........
0.814 to 0.820 Tar, juniper ..............
(n.Lt.) 1.099
Terebene ................
1.350 to 1.430 Wax, white and yellow ....
1.176 to 1.182 Whisky ..................
N.F.
1. 180 to 1.185 Anethol. ... : ..............
Ether, spmt of ...........
0.910 to 0.915 Ethyl acetate .............
0.945 to 0.965 Caramel.................
0.940 to 0~960 Hamamelis water...
0.918 to 0.927 Oil (fixed) of
0.914 to 0.921
croton ...............
0.915toO.921
sesame ................
0.925 to 0.935 Oil (volatile) of
0.910 to 0.915
birch tar. rectified .... '"
0.858 to 0.864
bitter orange ...........
caraway ...............
0.978 to 0.988
cardamom . . . . . . . . . . .
1. 038 to 1. 060
myrcia ................
(n.l.t.) 0.950
orange flowers ..........
1.045 to 1.063
pimenta........ ....
1.038 to 1.060
thyme .................
0.863 to 0.875 Tetrachlorethylene . . . . . .
1.047 to 1.050
(n.m.t.) 0.816
(n. m. t.) = not more than. (n. I. t.) = not less than. R. = reagent.
1 Saturated with water.
, Diluted with 2 times its volume of distilled water.
, At 100C. compared to water at 25C.
'At 30C.' compared with water at 15C .
At 60C.
Specific
gravity.
25C.
0.853 to 0.869
0.905 to 0.925
0.953 to 0.973
0.854 to 0.879
0.875 to 0.888
0.849 to 0.855
1.013 to 1.020
0.859 to 0.924
0.842 to 0.846
0.896 to 0.908
0.848 to 0.863
0.894 to 0.912
0.965 to 0.980
1. 065 to 1.077
0.917 to 0.934
0.960 to 0.990
0.854 to 0.868
0.853 to 0.862
(n.l.t.) 1.0
1.015 to 1.025
1.00 to 1.07
0.820 to 0.865
0.828 to 0.905
1.07 to 1 09
0.938 to 0: 944
(n.Lt.) 1.205
0.950 to 1.055
0.860 to 0 865
0.950 to 0:960
0.935 to 0.923
0.983 to 0.987
0.784 to 0.794
0.892 to 0.898
(n.l.t.) 1.35
0.979 to 0.982
0.935 to 0.950
0.916toO.921
0.886
0.845
0.900
0.917
0.962
0.863
1.018
0.894
1.600
to
to
to
to
to
to
to
to
to
0.950
0.851
0.910
0.947
0.990
0.880
1.048
0.930
1.610
CHAPTER XIII
227
10 cm. long; (2) a stirring rod bent into a circle at one end to fit
the above tube and at an angle at the other end to permit easy
manipulation; (3) a standard th~rmometer covering the desired
range of temperature; (4) an auxiliary thermometer to take the
emergent stem correction, preferably graduated from 20 to
100C.; (5) a capillary glass tube about 6 cm. long and 1.0 mm.
in diameter sealed at one end.
For temperatures up to 200C., a purified, concentrated sulfuric
acid is a suitable bath. For higher temperatures, up to about
350C., a pure grade of cottonseed oil (almost colorless) will
serve for a limited number of determinations. Other, though
less desirable, substitutes for sulfuric acid for use at high temperatures are: (1) a pure grade of paraffin which has been freshly
distilled; (2) clean, white, hydrogenated cottonseed oil. A very
satisfactory bath is prepared by cautiously boiling toge~her, for
from five to ten minutes under a hood, a mixture of 70 parts of
sulfuric acid and 30 parts of potassium sulfate, stirring constantly
until the potassium sulfate is completely dissolved.
The following exercise illustrates the methods used to determine the melting points of official substances:
Exercise 76
228
3. Introduce enough of the finely powdered dry salicylic acid into thc
capillary tube to form a column about 0.3 cm. in length.
The salicylic acid may be packed into the sealed end of the
tube by tapping the open end of it into a little mound of the powder, then inverting the tube and tapping it gently on a solid
surface, or by drawing the broad side of a triangular file across
the surface of the tube just below the powder.
4. Attach the charged capillary tube to the thermometer by wetting
both with the acid of the bath, and the tube will then be held in position by
capillary attraction, or attach the capillary tube by means of a rubber band,
clipped from a piece of rubber tubing, in such a position that the column of
salicylic acid is centrally located by the side of the thermometer bulb.
Attach the auxiliary thermometer so that the center of its bulb is as close as
possible to the stem of the main thermometer at a point midway between
the surface of the bath and the 160 graduation mark. Heat the acid bath
by means of a free Bunsen flame until a temperature of about 140C. is
reached, then carefully regulate the rise in temperature to about 3 per
minute until the substance begins to melt, and then regulate the rise in
temperature to about 0.5 per minute until the salicylic acid is completely
melted, while stirring the bath continually. Record the melting interval
temperature and the temperature registered on the auxiliary thermometer
at the end of the melting.
229
point, T the temperature at the end of melting, and t the temperature registered on the auxiliary thermometer. The correction is
added to the observed reading of the main thermometer; i.e.,
if in the determination of the melting point of salicylic acid, the
main thermometer is immersed in the bath to the 30 graduation
mark, the acid ~s completely melted at 156.5C. and the temperature registered on the auxiliary thermometer is 40C., the correction for the melting point temperature would be
0.00015 X 126.5(156.5 - 40) = 2.59C.
and the corrected melting point becomes 156.5 + 2.59 = 159.1C.
The melting point of a substance which cannot be readily
reduced to a powder is determined in the same manner with the
following exceptions: The substance is melted at as Iowa temperature as possible and drawn into a capillary tube, open at
both ends, to a depth of about 1 cm. The charged tube is allowed
to cool at 10C. or at a lower temperature for 24 hr. or in contact
with ice for 2 hr. The melting point of the substance is then
determined by attaching the charged tube to a standard thermometer as described in the above exercise or by means of a
rubber band and heating in a suitable bath so that the rate of rise
of temperature does not exceed 0.5 0 per minute for the last 5
before the expected melting point is reached. The temperature
at which the substance is observed to rise in the capillary tube
is taken as the melting point. Melting point determinations
by the above method are generally performed on substances
which are mixtures and which do not give the sharp melting
point characteristic of pure organic compounds.
Questions and Problems
1. Look up the melting points given for each of the following substances
in the U.S.P. and explain briefly why an interval of melting point temperatures is permitted in some cases while fixed melting points are given in
others: (a) paraffin, (b) petrolatum, (0) acetylsalicylic acid, (d) menthol,
(e) cocaine.
2. Why should thermometers for use in melting point determinations be
made of annealed glass? (See U.S.P., page 470.)
3. How might the emergent stem correction for the main thermometer be
determined by interpolation from a correction curve when a number of
melting points are to be determined? (See U.S.P., page 457.)
230
Substance
Melting
point.
Melting
point,
Substance
C.
U.S.P.
Acetanilid ................
Acetphenetidin ....... , ..
Acid, acetylsalicylic.... ..
Acid, benzoic .............
Acid. salicylio ....... , ....
Aminopyrine ............
Antipyrine ...............
Atropine .................
Atropine Bulfate. . . . . . . . . .
Barbital. ................
Benzidine, R .... , ........
BetanaphthoL ... " .......
Caffeine .................
Camphor ................
Carbromal ...............
ChlorbutanoL. . . . . . . . . . . .
Cocaine. . . . . . . . . . .. .....
Cocaine hydrochloride.....
Codeine (anhydrous) ......
Colchicine ...............
Dichloramine. . . . . . . . . . . . .
Dinitrophenylhydrazine R.
Diphenylamine, R. . . . . . ..
Ephedrine. . . .. . . . . . . . . ..
Ephedrine hydrochloride ..
Ephedrine sulfate .........
Ethyl ..minobcnzoatc. . . . ..
Ethyl morphine hydrochloride ............... .
Guaiacol ............... ..
Histamine phosphate ..... .
Homatropine hydrobromide... . . . . . . . . . . . . . . .
Iodoform.. . . . .. . . . . . . . . .
rsatin, R .................
Lard ................... ,
Menthol. . . . . . . . . . . . . . . ..
Methenamine. . . . . . . . . . . .
Neocinchophen. " . . . . . . . .
Oil. theobroma. . . . .. ....
Paraffin.
Petrolatum ...............
Phenacaine ...............
Phenacaine hydrochloride.
C.
U.S.P. (Oont.)
113 to 115
Phenobarbital. ...........
134 to 135
Phenolphthalein.. . . . . . . . .
(n.l.t.) 135*
Phenylsalicylate ...... " .
120 to 122
Phloroglucinol, R ..... " .
157
to 159
Pilocarpine nitrate .......
107 to 109
Procaine hydrochloride ...
111
to 113
Pyrogallol. ... ...........
114
to 116
Quinine ethylcarbonate....
(n.Lt.) 188
ResorcinoL ............
187 to 190
Saccharin..... ..........
127
to 129
Santonin .................
120 to 122
Scopolamine hydrobromide
235 to 237
Spermaceti. . . .. "
174 to 177
Suet, prepared. . . .. .
116
to 117
Sulfonethylmethane.... . ..
(n.Lt.) 78
Terpin hydrate ...........
Theophylline ............ '.
96 to 98
(n.Lt.) 183
Thymol. .. .. .. .. . .. . .. . ..
154 to 156
TrinitrophenoL ..........
142
to 146
Vanillin... . ............
(s.) 80
Wax (white aJ;)d yellow) ...
198 to 200
N.F.
52.5 to 53.5 Arecoline hydrobromide ...
34 to 40
Camphor, monobroma~d.
216 to 220
ChlorthymoL . . .
240 to 247.5 Cholesterol, R... . . .....
88 to 90
Chrysoidin, ba.se . ........ .
Cinchophen .............
123 (d.)
Cotarnine periodide .......
(a.) 28
Coumarin. . .. . . . . . . . . . . ..
(a.) 130
Dimethylaminoazobenzene,
(a.) 212(d.)
(a.) 115
198 to 201
36 to 42
41
to 43
(a.) 263
(n.l.t.) 74
30 to 35
50 to 57
38 to 54
195 to 197
(n.l.t.) 189
173 to 177
(n.l.t.) 258
41
to 43
216
to 219
170 to 173
153 to 156
130 to 133
89 to 91
109 to 111
(n.l.t.) 222
169 to 171
190
to 192
42
to 50
45
to 50
74
to 76
115
to 117
269
to 272
48 to 51
121
to 123
80
to 82
62
to 65
169
74
59
146
213
142
67
to 171
to 76
to 61
to 148
117
to 216
to 144
to 69
R ..................... 115
to 117
R.
73
214
48
85
86
145
to 75
to 220
to 50
to 90
to 88
to 147
240_
195
-l99
124
to
to
to
to
243
198
202
126
reagent .
231
232
the bulb, the total length of the thermometer being about 38 cm. The bulb
should be about 3 cm. long and 6 mm. in diameter, the scale should be
etched on, and the graduations clear-cut and distinct. The thermometer
should be made of the best thermometric glass and thoroughly annealed, so
that scale errors will not increase after continued heating."
Procedure.-l. "Heat 75 cc. of glycerin-potassium hydroxide solution
(made by dissolving 25 Gm. of potassium hydroxide in 100 cc. of glycerin)
to 150C. in an 800-cc. beaker and add 50 cc. of the clarified fat, melted if
necessary. Heat the mixture for fifteen minutes with frequent stirring, but
do not allow the temperature to rise above 1500. When saponification is
complete, the mixture is homogeneous, with no particles clinging to the
beaker at the meniscus."
233
Then allow the thermometer to hang quietly, the bulb in the center of the
acids and observe the rise of the mercury column. The highest point to
which it rises is the Solidifying Point of the fatty acids."
Substance
U.S.P.
Acid, glacial acetic ........................ .
Acid, oleic. . . . . . . . . . . . . .. ............. "
Acid, stearic ............................. .
Benzene, R .............................. .
Eucalyptol. .............................. .
Fatty acids from
oil, almond, expressed ................... .
oil, cottonseed. . . . . .. . ................ .
oil, olive. . . . . . . . . . . . . . . . . . . . . . . . .. . .. .
oil, theobroma. . . . . . . . . . . . . . . . .. . ..... .
soap, hard ........................... .
sodium stearate. . . . . . . . . . . .. . ......... .
zinc stearate. . . . . . . . . . . .. . ........... .
Oil of anise .............................. .
Oil of eucalyptl,ls. . . . .
. ........... .
Oil of fennel. . . . . . . ............ .
Paraldehyde. . . . . . . . . . . . . . . . . .. . ...... .
Phenol. ................................. .
Phenylhydrazine, R ....................... .
Suet, prepared ........................... .
Congealing
Point, cC.
(n.l.t.) 145
(n.m.t.) 10
(n.l.t.) 54
(n.l.t.) 5.2
(n.l.t.) 0
9 to 12
28 to 35
17 to 26
45 to 50
18 to 23
(n.l.t.) 54
(n.l.t.) 54
(n.l.t.) 15
(n.l.t.) 15.4
(n.l.t.) 3
(n.l.t.) 11
(n.l.t.) 39
(n.l.t.) 16
37 to 40
N.F.
Anethol. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20 to 21
o-Toluidine, R ............................ (n.m.t.) 20
(n.m.t.) = not more than. (n.l.t.) = not less than. R. = reagent.
234
The boiling point of any liquid may be defined as that temperature at which the vapor pressure of the liquid is equal to the atmospheric pressure. Where a given temperature is stated as the
boiling point of a liquid, the inference is that the corresponding
pressure is standard atmospheric pressure, 760 mm., unless
otherwise given.
In the Pharmacopoeia, the boiling point is defined as that range
of temperature within which at least 95 per cent, by volume, of
the substance distils when treated in a definite manner.
The apparatus to be used (Fig. 27) and its construction are as
follows:
235
236
barometric pressure from the normal (760 mm.) by allowing O.lC. for each
2.7 mm., adding if the pressure is lower, and subtracting if higher than
760 mm.
237
238
Substance
Boiling Point, cC.
U.S.P.
Amyl alcohol, R ........................ 128 to 132
Aniline, R ............................. )83 to 186
Benzene, R .............. ' .. .. ...... ... 79.5 to 81
Benzin, purified petroleum. . . . . . . . . . . . . .. 35 ~O 80
Butyl alcohol, R ........................ 116 tb 118
Carbon disulfide, R. . . . . . . . . . . . . . . . . . . .. 76 to 78
Carbon etrachloride. . . . . . . . . . . . . . . . . . . .. 76 to 78
Ethyl a tetate, R. . . . . . . . . . . . . . . . . . . . . .. 76 tb 77.5
Ethyl chcloride. ... . .. . . . . . . . . . . .. . . . . .. 12 to 13
Eucalyptol. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 174 to 177
Eugenol ............................. " 250 to 255
Furfural, R, ........................... 150 to 152
Guaiacol, solid. . . . . . . . . . . . . . . . . . . . . . . . .. 204 to 206
Kerosene, R ............................ 180 to 300
Methanol, R.. ........................ 64 to 67
Methyl salicylate ....................... 219 to 224
Oil of mustard, volatile .... , ............. 148 to 154
Paraldehyde. . . . . . . . . . . . . . . . . . . . . . . . . . .. 120 to 125
Terebene .............................. 160 to 172
Toluene, R ............................. 110 to 111
Xylene, R .............................. 137 to 140
N.F.
Ethylacetate.......................... 75 to 77
Anethol. ... : ... . . . . . . . . . . . . . . . . . . . . . . . .. 234 to 237
R. = reagent.
239
CHAPTER XIV
REFRACTOMETRIC MEASUREMENTS
itEFRACTOME'l'RIC MEASUREMENTS
241
242
FIG.
REFRACTOMETRIC MEASUREMENTS
243
244
REFRACTOMETRIC MEASUREMENTS
245
Exercise 78
The refractiye index of the test plate is etched upon it, and the
reading of th~instrument should correspond to that given on this
plate. If thtJ instrument is not in adjustment, a correction should
be applied to the readings obtained.
2. Remo'l{e the test plate, clean the upper prism with cotton saturated
with alcohol, clamp the prisms together loosely, introduce 2 or 3 drops of
the volatilll oil into the groove at the side of the prisms, and clamp the
prisms together firmly. Adjust the mirror K so that the light is reflected
upon the lower prism, and rotate the alidade until the border line between
the lightl and dark halves of the field of view exactly coincides with the
cross-hai,'rs of the telescope, rotating the compensator prisms to obtain a
sharp uncolored border line if necessary. Read the refractive index of
the oil directly from the graduated sector scale to the fourth decimal place.
Move the aJidade and again determine the refractive index until three
readings are obtained, taking the mean of the readings as the refractive
index of the oiL Note the temperature at which the refractive index is read.
246
3. A range is given for the refractive index of most of the official volatile
oils. Why?
4. How do variations in temperature affect the inqices of refraction of
liquids?
6. Would you expect that oil of orange would have a greater or smaller
index of refraction at 25 than at 20C.? Why?
TABLE
XXXIV.-OFFICIAL
SUBSTANCES
WITH
I
RE~UlRED
REFRACTIVE
INDICES
Substance
U.S.P.
Eucalyptol. ......................
Oil of anise .......................
Oil of bitter almond ...............
Oil of chenopodium ...............
Oil of cinnamon ...................
Oil of clove .......................
Oil of coriander ...................
Oi~ of dwarf pine needles ...........
Oil of eucalyptus ..................
Oil of fennel. .....................
Oil of juniper .....................
Oil of lavender ....................
Oil of lemon ......................
Oil of mustard, volatile ............
Oil of myristica ......... .........
Oil of orange .....................
Oil of peppermint .................
Oil of rose ........................
Oil of rosemary ...................
Oil of santal. .....................
Oil of sassafras ...................
Oil of spearmint ..................
Oil of theobroma ..................
Oil of turpentine ..... , ............
N.F.
Anethol. .........................
Oil of caraway ....................
Temperature,
Official requirement
C.
20
20
20
20
20
20
20
20
20
20
20
30
20
20
20
20
40
20
1.455 to 1.460
1. 5530 to 1. 5600
~.5428to 1.5439
1. 4723 to 1. 4790
1 .'6020 to 1. 6135
1. 5300 to l. 5350
1.4620 to 1. 4720
1. 4580 to 1. 4700
1 . 4600 to 1. 4690
1 . 5280 to 1. 5380
1. 4780 to 1. 4840
1. 4590 to 1. 4700
1.4742 to 1.4755
1 . 5268 td 1. 5280
1. 4740 to'!. 4880
l.4723 to'1.4737
l. 4600 to'!. 4710
1.457 toh.463
1. 4640 to b. .4760
1.5000 to 1.5100
1 . 5250 to 1. 5350
1. 4820 to 1'.4900
1 . 4537 to 1. 4578
1. 4680 to 1. ~ 780
25
20
1. 5580 to 1. 5~10
1.484 to 1.488
20
20
20
20
20
20
CHAPTER XV
ROTATORY POWER
Many organic substances, such as certain constituents of the
volatile oils, alkaloids, and sugars, possess the power of rotating
the plane of polarized light when the latter is passed through
solutions containing them. Substances which possess this power
are said to be optically active and are designated as dextrorotatory when the direction of the rotation is toward the right and as
laevorotatory when it is toward the left.
The optical activity of many substances is a function of their
chemical constitution as well as of their concentration. Consequently, a determination of the rotatory power or lack of
rotatory power of a substance may serve as a means of establishing both its identity and its purity. In some cases, the me asu~ement of the optical activity of a substance may also give
some indication of its therapeutic value; e.g., the laevorotatory
alkaloid hyoscyamine is much more active as a mydriatic than
its optically inac.tive isomer atropine.
In a ray of ordinary light, the vibrations are transverse, i.e.,
they take place in a. plane at right angles to the direction of
propagation, but the vibration direction is constantly changing.
In a ray of plane-polarized light, commonly termed polarized light,
the vibrations are also transverse, but they take place in only
one direction.
The polariscope and the polarizing microscope are used in the
determination of the optical activities of liquid and solid substances, the polarizing microscope being employed more often
for the examination of solid SUbstances, while the polariscope
is used primarily for the examination of liquids.
When a ray of ordinary light is passed through a specially
constructed prism made of Iceland spar, such as the Nicol's
prism, the emergent light wave vibrations take place in one
plane, and the light is' said to be plane-polarized. If another
247
248
ROTATORY POWER
249
lOOa
lpd
or [alb
l~a
ia
250
,,~F
r
l\'
,. . ----------.1
lI/E ISID,~-=,=o;::::==:i~,lc ISIB
AO,~R{
~1f,"!.A
ClW
FIG. 34.-Diagram of the optical parts of a polarimeter.
ROTATORY POWER
251
252
ROTATORY POWER
253
254
th~
official
Official Requirement
= Angular rotation
Substance
U.S.P.
Copaiba, volatile oil from ....
Methyl salicylate from gaultheria ....................
Oil of anise .................
Oil of bitter almond. . . .. . ..
Oil of cinnamon. . . . . . . . . .. .
Oil of clove. . . . . . . . . . . . .
Oil of coriander. . . . . . . . . . ..
Oil of fennel. ...............
Oil of juniper. . . . . . . . . . . . . ..
Oil of lavender ..............
Oil of lemon. . . . . . . . . . . . . ..
Oil of dwarf pine needles .....
Oil of myristic a . . . . . . . . . . . ..
Oil of orange .... ,. . . .. . ....
Oil of peppermint ...........
Oil of rose ..................
Oil of rosemary .............
Oil of santal. ...............
Oil of sassafras ..............
Oil of spearmint .............
Terebene. . . . . . . . . . . . . . . . . ..
a = 1 to 40
a = 5 to +10 0
a = -15 to -20 0
a = +2 to +4 0
a = -48 to -59 0
a = not more than +0.3 0
N.F.
Anethol. . . . . . ... . . . . . . . . . . ..
Oil of bergamot .............
Oil of bitter orange. . . . . . . . ..
Oil of caraway ..............
Oil of cardamom ............
Oil of myrcia ................
Oil of orange flowers. . . . . . . ..
Oil of pimenta ..............
Oil of thyme .... , ...........
Salicin. . . . . . . . . . . . . . . . . . . ..
a = 0 to +0.08 0
a = +8 to +240
a = +88 to +980
a = +70 to +80 0
a = +22 to +440
a = not more than _3 0
a = + 10 3~' to +9 0 8'
a = 0 to _4
a = not more than 4 0
a = 62 to 67 0
255
ROTATORY POWER
5. Explain what the following terms mean: (1) [aut = +4.210; (2)
= -10; (3) dextrorotatory; (4) optically inactive.
6. The optical rotation of a sample of oil of chenopodium determined in a
100 mm. tube and having a density of 0.9750 is found to be -12.25 deg.
at 21. Calculate the specific rotation of the oil.
7. A sblution containing 10 Gm. of sugar in 100 cc. was found to exhibit
an angular rotation of +11.5 deg. when determined in a 100 mm. observation tube. Calculate the specific rotation of the sucrose.
[aUf
Substance
U.S.P.
Camphor" natural
Dextrose .........
Ephedrine hydrochloride ........
Ephedrine sulfate ..
Epinephrine ......
Oil, chaulmoogra ..
Ethyl chaulmoograte ...........
Lactose ...........
Scopolamine hydrobromide .....
Sucrose ..........
N.F.
Ephedrine sulfate,
solution of ......
Solvent
used
Concentrationin
.100 cc.
[alD =
[aut =
specific rotation
Alcohol
Water
10 Gm.
10 Gm.
Water
Water
0.5 N HCI
Chloroform
5Gm.
5Gm.
5 Gm.
10 Gm.
[aut
[aut
[aut
[alit
Chloroform
Water
50 cc.
[a]i,s = not less than +44.5
10 Om. [aUf = +52.2 to +52.5
Water
Water
Water
3 Gm.
=
=
=
=
+41 to +42
-33 to -35.5
-29.5 to -32 0
-50 to -53.5
+48 to +60
256
CHAPTER XVI
VISCOSITY MEASUREMENTS
258
VISCOSITY MEASUREMENTS
259
The water in the temperature bath should be stirred continually to insure an even distribution of temper~ture throughout
the sample of oil.
2. When the -thermometer in the oil cup registers exactly 37.8C., remove
the cork from the outlet tube, starting the stop watch at the same instant,
and collect the effluent oil in the flask graduated to hold 60 cc. When the
level of the oil in the flask reaches the 60 cc. graduation mark, stop the
watch.
The time in seconds required for the efflux of 60 cc. of the liquid
petrolatum is called the Saybolt universal viscosity.
The U.S.P. requires that liquid petrolatum have a kinematic
viscosity of not more than 0.370 at 37.8C. (lOOF.). This value
is equivalent to a Saybolt universal viscosity of 170.
Questions and Problems
1. Consult the viscosity conversion table (U.S.P., page 477) and express
the results obtained in the above exercise in terms of kinematic viscosity
and in terms of Engler degrees.
2. If the viscosity of a sample of liquid petrolatum is found to be less than
thc official requirement, what does the determination indicate relative to
the composition of the oil?
3. Would viscosity requirements be of value as a constant for (1) glycerin,
(2) castor oil, (3) simple syrup?
CHAPTER XVII
PHOTOMETRIC METHODS OF ANALYSIS
FIG.
37.-Nessler apparatus.
261
262
263
3. Look up Beer's law in a textbook of physics and explain what application if any is made of that law in colorimetric analysis.
4. Review the Gunning-Kjeldahl method of estimating nitrogen in organic
compounds and briefly explain how that method combined with the colorimetric method might be used to determine the nitrogen content in very
small amounts of certain organic compounds.
264
265
C2
266
267
268
O2 = 0 1 X L1
L2
Questions and Problems
1. Would it be practicable to replace the present official test for arsenic
(see U.S.P., page 436) by a nephelometric method?
269
270
271
Those who desire to make a more extended study of photometric, methods of analysis will find a very comprehensive treatment
of the subject and an extensive bibliography in "Photometric
Chemical Analysis," by J. H. Yoe (2 vols., John Wiley & Sons,
Inc., New York, 1929).
CHAPTER XVIII
DETERMINATION OF HYDROGEN ION CONCENTRATION
H+
+ A-
IB +H+
B+
272
+ OH-
273
For the purpose of this discussion, salts, certain acids, and the
hydroxides of the alkali metals are assumed to be completely
dissociated in dilute aqueous sE>lution.
At equilibrium the ordinary mass action equation will hold as a
first approximation for weak acids
[H+][A-] = Ka
[HA]
[A-]
Ka
[HA] = [H+]'
(1)
(2)
or
log [H+]
(3)
274
Normality,
hydrogen ions
Normality,
hydroxyl ions
1
10-1
10-2
10-3
10-<
10-'
10-
10- 7
10-s
10-'
10-1
10-11
10- 12
10- 13
10-14
10-14
10-13
0
1
2
3
4
5
6
Neutral potnt 7
8
9
10
11
12
13
14
10-12
10- 11
10- 10
10-
10-8
10-7
10-
10-'
10-4
10-3
10- 2
10- 1
1
TABLE XXXVIII
[H+]
pH
CorrespondIng Change
COO
0.70
O.~O
1.5
1.1
1.05
1.023
0.04
0.02
0.01
0.18
log [HA]
+ log Ka
(4)
= pH
ia
ia
will be
by two units,
ia
When pH,
within
2 units log
i,,'
275
2H+
+ 2e
E = RT In (H+)'yPH2
F
(H+)yP'H2
+E
(5)
L,
Where (H+)' is the activity of the hydrogen ions in the halfcell having the greater hydrogen ion activity, P'H2 is the hydrogen
pressure in the same half-cell and EL is the potential jump at the
liquid junction of the half-cells. The latter is not eliminated
but is reduced to a small, usually neglected value, by making the
junc,tion with saturated potassium chloride solution.
The ultimate standard of reference is the hydrogen half-cell
in which the hydrogen ion activity is :unity and the hydrogen
pressure is one atmosphere. If this half-cell were used in conjunction with another half-cell of lower hydrogen ion activity and
the hydrogen pressure were the same in the two half-cells, then
RT
1
E = FIn (H+)
or
~
1
E = 0.0581 log (H+)
(6)
(7)
276
IunSkolution ofH
IPt,
p
~nown
H2 (1 atmos.)
E - 0.2488
0.0581
(8)
277
concentration of solutions can also be determined colorimetrically (see page 297). The potentiometric method, however, is
more accurate in general and is to be preferred even though it
requires a more elaborate apparatus and more experience on the
part of the analyst.
Potentiometric Methods.-When an acid or an alkali is dissolved in water, the characteristic properties of the solution
obtained are due to the hydrogen and hydroxyl ions formed by
the dissociation of the acid or base. The effective acidity
or alkalinity depends on the extent of dissociation of the acid
or base in solution and is independent of the total acidity or
alkalinity. In the volumetric estimations of acids and alkalies,
the total acidity or alkalinity is determined. In measuring
the effective acidity or alkalinity (the strength of the acid or
base) of a solution, however, it is necessary to determine the
hydrogen ion concentration.
The hydrogen ion concentration of an aqueous solution may be
determined by measuring the voltage developed between two
electrodes of special character immersed in the solution by means
of a potentiometer, since the voltage developed between the
electrodes directly depends on the concentration of hydrogen
ions in thc solution. The measurement of the voltage produced
between the electrodes is equivalent, therefore, to a determination
of the hydrogen ion concentration and to the determination of the
effective acidity or alkalinity of th~ solution.
The electrodes employed in the determination of hydrogen ion
concentration must be of such character that one of them will
develop a potential that varies according to the concentration of
hydrogen ions, and the other must have a constant potential
unaffected by the hydrogen, ion concentration. Although a number of electrodes of different character have been developed for
use in potentiometric methods of hydrogen ion concentration
measurements, the fundamental method involves the use of the
so-called hydrogen electrode an'd. the saturated calomel electrode
described here.
The hydrogen electrode (Fig. 40) consists of a small square of
platinum foil attached to a short piece of platinum wire sealed
into and extending through one end of a glass tube. Mercury
is poured into the open end of this tube to cover the platinum wire
278
279
with distilled water, immerse it in dilute sulfuric acid, and electrolyze as cathode for 1 or 2 min. to saturate the platinum black
with hy9-rogen. Suspend the electrode in distilled water until it
is used.
The calomel electrode (Fig. 41) is prepared as follows: Add 200
Gm. of pure potassium chloride to 500 cc. of hot distilled water
contained in a 1,000 cc. beaker, add 0.5 Gm. of pure mercurous
chloride (calomel) to the hot solution, and stir the mixture well.
Allow the mixture to cool to room temperature and filter out the
e~cess potassium chloride and calomel. Store the solution in a
well-stoppered bottle for future use. Clean the electrode
vessel thoroughly by washing it successively with cleaning
mixture and distilled water. Dry the vessel. Pour pure mercury into the electrode vessel until the platinum wire in the
bottom is covered. Add a layer of mercurous chloride about a quarter ineh deep
over the mercury, pour some of the potassium chloride-calomel solution 0 V e r it, +
stopper the mouth of the vessel, close the
stopcock, and shake the contents together,
being careful to avoid as far as possible
getting mercury and calomel into the side
arm. Allow the mixture to settle and fill
the vessel and side arm with the potassium
chloride-calomel solution, wash away any
floating calomel by overflowing, make ~_flL"DINARY M<IOCU".
certain that no air bubbles are trapped FIG. 41.-Calomel eleotrade.
in the side arm, and close the stopcock.
Stopper the electrode vessel until it is ready for use. Fill
the side tube connecting with the bottom of the vessel with
ordinary mercury so that the platinum wire that extends into
this tube from the vessel is covered.
Only the purest obtainable chemicals should be used to prepare the calomel electrode. Specially purified mercury, calomel
produced by electrolysis, and analyzed potassium chloride can
be obtained from supply houses for this purpose.
The potential developed by the calomel electrode depends on
the concentration of potassium chloride used and is independent
of the hydrogen ion concentration of the solutions examined
280
XXXIX
Potential at
Calomel eleotrode
20C.
0.1 N KCl. ...................
NKCl. ......................
Saturated KCl. ...............
0.3379
0.2860
0.2496
25C.
0.3376
0.2848
0.2458
30C.
0.3371
0.2835
0.2420
281
Object.-To Determine the End Point of Titration of Hydrochloric Acid with Sodium Hydroxide Potentiometrically.
Materials Required.-A potentiometer.
A galvanometer.
A standard cell.
A storage battery.
A hydrogen electrode.
A calomel electrode.
A cylinder of compressed electrolytic hydrogen 100 or 200 cu. ft. capacity,
equipped with a pressure-reducing valve.
Two gas-washing bottles.
An aspirator bottle.
12 to 20 ft. of well-insulated, IS-gage copper wire.
3 titration beakers, 50 to 200 cc. capacity.
282
283
284
o ABC
'~ (
\ \\
Z
3
4
5
pH
6
7
8
9
10
1
12
13
\\1\
\~\
~ \\
\\\
'\ \\
1\\\
\ l\\
.~ l\
~\\
"\ \\
\\\
\
l\\
\) l\
140.2 0.3 0.4 0.5 0.9 0.1 0.8 0.9 1.0 1.1 1.2
Voltage
FIG. 43.-Graph showing relation of pH and voltage measured with hydrogen
and calomel electrodes.
285
3 4 567 6 9 W
~ n
E IT ffi
II.
IJ/.
ma/NaOff
IOcc.Orlhophosphoric
Acid-O.! NormaJ NaOIi
V. iOcc.NeQr/ySaturtried
BoricAcia-Norma/ NaOH
5~
6~
<
7~
9~
IO~
II;
IZ~
13:
14'
286
287
690.5; 31 cc. = 860.1; 35.0 cc. = 949.5; 40 cc. = 965.9; 45 cc. = 982.2;
50 cc. = 992.1. Plot the millivolts of electrode potential as ordinates and
the cubic centimeters of NaOH as abscissae. Determine the pH value at
the end point from the curve and calculate the normality of the sodium
hydroxiae solution.
Exercise 88
Object.-To Determine the- pH of Saturated Boric Acid Solution, and Physiological Salt SolutIon.
Materials Required.-25 or 50 cc. of each of the above solutions.
The titration apparatus described in Exercise 87.
Procedure.-Determine the pH of each solution separately. Place the
respective solutions in the titration beaker, allow the hydrogen gas to flow
until the electrode has come to equilibrium with the voltage. Take three
voltage readings at 1 min. intervals. Calculate the pH of the solution from
the data obtained.
288
quinone
+ hydroquinone
+ 2H + 2( -
hydroquinQne
The ratio of quinone to hydroquinone in acid 'solution is maintained constant by the presence of undissociated quinhydrone
in solution. When this condition obtains, the potential at the
electrode is a function of the hydrogen ion concentration of
the solution. In carrying out determinations, the potential
is measured against that of a calomel electrode, and the pH
value is calculated from the measured voltage in the same
manner as with the hydrogen electrode.
The potential of the quinhydrone electrode is higher than
that of the hydrogen electrode in the same solution. If a
saturated calomel electrode is used and the measurement is
carried out at 25C., the pH may be calculated from the equation:
0.453
- V
h
V'IS th e measure d vo1tage.
0.0591
= I
og I
H+ = PH were
289
1\
pH
10
- 0.2
- 0.1
Voltage
.. 0.1 .. O.l.
290
Gl!::'
291
292
293
Indicator
XL.-pH
pH range
INDICATORS
MolecuJar
weight
Color change
Solvent
to
to
to
to
to
to
to
to
4.0
4.6
6.3
6.8
7.6
8.4
9.6
10.5
225
669
269
540
624
354
466
430
Red-yellow
Alcohol
Yellow-blue
3.0 cc. 0.05 N
Red-yellow
7.4 cc. 0.05 N
Yellow-purple 3.7 cc. 0.05 N
Yellow-blue
3.2 cc~ 0.05 N
Yellow-red
5.7 cc. 0.05 N
Yellow-blue
4.3 cc. 0.05 N
Colorless-blue
Alcobol
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
Solutions Used in the Preparation of Buffer Solutions.Fifth molar hydrochloric acid and 0.2 M sodium hydroxide
(carbonate-free) are prepared and standardized according to
the directions given under Standard Solutions.
294
Luns
HCI-KCI Mixtures
pH
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
1.9
2.0
2.1
2.2
0.2 M KOI,
CC.
5.44
24.90
40.32
52.60
62.36
70.06
76.24
81.14
85.02
88.10
90.64
92.48
94.56
75.10
59.68
47.40
37.64
29.90
23.76
18.86
14.98
11.90
9.46
7.52
200
200
200
200
200
200
200
200
200
200
200
200
Phthalate-Hel Mixture
pH
2.2
2.4
2.6
2.8
3.0
3.2
3.4
3.6
3.8
50
60
60
50
50
50
50
50
50
0.2 MHCI
46.60
39.60
33.00
26.50
20.40
14.80
9.95
6.00
2.65
J:?ilute to,
00.
200
200
200
;ZOO
200
200
200
200
200
Phthalate-NaOH Mixtures
pH
4.0
4.2
4.4
4.6
4.8
5.0
5.2
5.4
5.6
5.8
6.0
6.2
50
50
50
50
50
50
50
50
50
50
50
50
0.40
3.65
7.35
12.00
17,50
23.65
29.75
35.25
39.70
43.10
45.40
47.00
200
200
200
200
200
200
200
200
200
200
200
200
295
LUBS.-(Continued)
KH.PO.-NaOH Mixtures
pH
5.8
6.0
6.2
6.4
6.6
6.8
7.0
1.2
7.4
7.6
7.8
8.0
50
50
50
50
50
50
50
50
50
50
50
50
3.66
5.64
8.55
12.60
11.14
23.60
29.54
34.90
39.34
42.14
45.17
46.85
Dilute to,
CC.
200
200
200
200
200
200
200
200
200
200
200
200
pH
7.8
8.0
8.2
8.4
8.6
8.8
9.0
9.2
9.4
9.0
9.8
10.0
50
50
50
50
50
50
50
50
50
50
50
50
2.65
4.00
5.90
8.55
12.00
16.40
21.40
26.70
32.00
36.85
40.80
43.90
200
200
200
200
200
200
200
200
200
200
200
200
296
297
298
0.5 cc. of the indicator solution to each of them, and then sealing
the tubes. Thus in preparing color standards for phenol red
10 cc. of nine buffer mixtures having pH values of 6.8, 7.0, 7.2,
7.4, 7.6, 7.8, 8.0, 8.2, and 8.4, respectively, are placed in separate
tubes, 0.5 cc. of 0.02 per cent phenol req. indicator solution is
added to each tube, and the tubes are sealed. Each tube is
then labeled with the respective pH value corresponding to
that of the buffer solution which it contains. The tube marked
pH 6.8 will exhibit the yellow color and that marked pH 8.4 will
exhibit the red color of phenol
red, and the tubes with intermediate pH values will show
gradations of color between
yellow and red.
Reliable color standards
covering the pH range 1.2 to
10.4 for all of the required
indicators, guaranteed for one
year, can be purchased. It is
unnecessary to secure color
standards for all of the indicat ors cove ring the range
FIG. 48.-Block comparator.
pH = 1.2 to 10.4 unless determinations of pH on a variety of products of widely divergent
hydrogen ion concentration are to be made. Thus if a solution
has a pH falling between 6 and 8.4, color standards for bromthymol blue and cresol red are all that is necessary.
Color Comparators.-Some type of color comparator must be
used to match the color of the unknown with the color standards.
This is especially true if the sample under examination is at all
turbid or colored. Of the numerous devices available, the
LaMotte block comparator (Fig. 48) is 1>est suited for use with
the equipment herein described. This comparator consists of
anyone set of color standards such as bromthymol blue; four
test tubes graduated at 10 cc. and of the same bore and wall thickness as the color standard tubes; and a 50 cc. bottle of the corresponding indicator solution; a tube of distilled water; and a
pipette contained in a wooden case. The top of this case is so
designed that it may be removed and used as a comparator
block.
299
The block comparator is used as follows: Assume that a preliminary test made with various indicators or a mixed indICator
shows that the solution being tested has a pH falling between
pH 6.0 and 7.5. A set of bromthymol blue color standards and
indicator would then serve for the determination. To make the
determination, remove the top of the comparator case (Fig. 48),
and use it as a comparator block. The six holes back of the slots
in the side of this block are desigB
A
c
nated B, A, C and E, D, F, respectively, in Fig. 49.
Fill three of the test tubes to the
10 cc. graduation mark with the
liquid to be tested and place them in
the holes marked B, A, and C. Add
0.5 cc. of bromthymol blue to the
F
D
tube in A and shake the tube well to
.E
mix the contents. Place the tube con- FIG. 49.-Positions of tubes
in the block comparator.
taining distilled water in the hole
marked D, and two of the tubes containing color standards
differing only by 0.2 pH, e.g., 6.8 and 7.0, in the holes E
and F, respectively. Place the comparator block before a
window or other source of light, observe the three pairs
of tubes through the slots, and change the color standards
in E and F, if necessary, until the color of the central pair exactly
matches the color in one of the other pairs or until the color of
the central pair lies between that of the pairs on either side.
If the color of the solution in the central pair matches that of one
of the other pairs, the pH is read off on the color standard with
which the match is obtained. If, however, the color of the solution in the central pair of tubes lies between the colors of the
pairs on either side, the average pH of the latter is taken as the
pH of the sample; e.g., if it lies between 7.0 and 7.2, the value
is taken as 7.1.
The LaMotte roulette comparator (Fig. 50) is designed for
rapid pH determinations with artificial illumination. This comparator consists of a stationary base and metal band, and a
wooden drum which revolves inside the band on ball bearings.
Illumination is provided by a 40-watt Mazda lamp attached in
the center of the base. A piece of "Dalite" glass is placed in the
000
000
300
back of the block between the three test tubes and the color
standards, and a piece of etched glass is placed on the outside
of the block directly over the three slots. This contrivance provides standard conditions of illumination at all times. Ampoules
of distilled water, bottles of indicator solution, graduated test
tubes, and pipettes are a part of the comparator equipment.
Any three sets of color standards such as chlorphenol red,
pH 5.2 to 6.8; bromthymol blue, pH 6.0 to 7.6; and phenol
red, pH 6.8 to 8.4 are placed in alternate holes in the revolving
drum in the order of their pH. Tubes of the same bore filled
with distilled water are then placed in the vacant holes. There
FIG.
will then be :3, tube of distilled water beside each tube of color
standard. If the pH of the solution to be tested falls somewhere
within the range of bromthymol blue, pH = 6.0 to 7.6 as determined by preliminary tests (see page 296), fill three of the test
tubes to the 10 cc. graduation mark with the solution and place
them in the three holes in the block. Add 0.5 cc. of bromthymol
blue to the middle tube and mix it in well by shaking. Turn on
the light and revolve the drum until the bromthymol blue color
standards are directly behind the test sample. While looking
through the slots in the block, gradually shift the standards by
rotating the drum until the color through the test sample exactly
matches that of one of the tubes on either side of it or lies between
them. The pH value may then be read off directly from the color
standards in the same manner as with the block comparator.
301
Exercise 91
302
XLII.-pH
Substance
Concentration
0.1 M
Saturated fjolution
0.1 M
0.1 M
0.1 M
0.1 M
0.1 M
0.1 M
0.1 M
0.1 M
Saturated solution
0.05 M
0.1 M
0.1 M
0.05M
0.1 M
0.1 M
0.1 M
0.1 M
1 in 300
1 in 20
Saturated solution
1 in 100
1 in 25
1 in 25
0.2 M
0.2 M
Saturated solution
1 in 25
Saturated solution
0.1 M
Saturated solution
0.1 M
0.1 M
1 in 50
1 in 200
1 in 200
1 in 100
0.2 M
0.1 M
1 in 200
1 in 100
pH
2.9
2.8
5.1
2.1
1.0
1.0
1.5
2.4
1.1
1.5
2.4
1.2
1.9
1.2
4.6
4.2
4.6
4.6
11.3
4.8
3.0
\9.5
5.4
2.3
7.4
8.0
7.0
6.5 to 7.5
13.5
6.0 to 7.0
6.4
4.5
9.8
4.5
5.0
5.6
to
10.8
5.1
4.4
10.6
6.0to7.0
4.8
5.8
4.8
XLIL-pH
OF SOME OFFICIAL
Substance
Potassium acetate .................... .
Potassium bicarbonate ..... , ..... : .... .
Potassium bromide ... ,'. , , ............ .
Potassium carbonate ...... , , ......... .
Potassium hydroxide ................. .
Potassium iodide .............. , ...... .
Potassium nitrate .................... .
Potassium and sodium tartrate ... , .... .
Procaine hydrochloride ............... .
Quinidine sulfate ... , ....... , ......... .
Quinine ............................. .
Quinine bisulfate ..................... .
Quinine dihydrochloride .. , , .......... .
Quinine hydrobromide ................ .
Quinine hydrochloride ............... , .
Quinine sulfate ..... , ..... , ........ , :.
Quinine and urea hydrochloride ........ .
Sodium acetate ...................... .
Sodium benzoate ..................... .
Sodium bicarbonate .................. .
Sodium biphosphate .......... , ....... .
Sollium borate .... ,., , ...... , ....... :.
Sodium bromide, . , ....... , .......... .
Sodium cacodylate, ........ , ...... , .. .
Sodium carbonate, ..... , , ........ , ., ..
SQ.dium chloride ... , ................. .
Sodium hydroxide .................... .
Sodium iodide ....................... .
Sodium phosphate (dibasic) ........... .
Sodium salicylate. , .................. .
Sodium sulfate ............ , .......... .
Sodium thiosulfate ..... , ............. .
Soluble barbitaL, .................... .
Strychnine nitrate ........... .' ...... , ..
Strychnine sulfate .................. , ..
Theobromine with sodium salicylate ... .
303
SUBSTANCES.-(Continued)
Concentration
pH
0.1 M
9.7
0.1 M
8,2
0.2M
6,5 to 8.0
0.1 M
11..6
0.1 M
13.5
0.2M
.7.0 to 9.0
0.2M
6.5 to 7.5
0.2 M
7.0to8.0
0.1 M
6,0
1 in 200
6.4
Saturated solution
8.8
1 in 25
3.5
1 in 25
2.6
1 in 25
6.4
1 in 25
6.'4
Saturatt;ld solution
6.2
1 in 20
3.1
0,1 M
9.7
0.1 M
8.0
0.1 M
8.2
0.1 M
4.5
9.2'
0.1 M
0.2 M
6.5 to 8.0
0.1 M
7.8
0.1 M
11,6
0.2M
6.7to 7.3
0.1 M
13.5
0.2 M'
8.0 to 9.5
0.1 M
9.5
0.2 M
5.0 to 6.0
0.2 M
6,0 to 7.5
0.2M
6.5 to 8.0
0.1 M
9.4
1 in 250
5.7
1 in 100
5.5
1 in 100
10.3
they usually occur on the market, will falL Some deviations from
these values may, however, be expected, as the presence of even
a very slight excess of base or acid in these salts, or of carbon
dioxide in their solutions, exercises a pronounced influence upon
the hydrogen ion concentration.
304
CHAPTER XIX
ELECTROLYTIC METHODS
Quantitative analysis by means of electrolysis, or electroanalysis, as it is more generally called, is usually restricted to the
determination of metals. This method of analysis is based upon
the fact that an electrical current passed through a solution of
the salt of a metal causes the deposition of the metal, usually
in the elemental state, upon one of the electrodes. The electrolytic method may be applied to a number of official substances,
namely, mercury and its salts and the salts of silver, copper, and
zinc.
Electrical Units and Fundamental Laws.-The unit of current
is the ampere, that of resistance is the ohm, and that of difference
of potential or el~ctromotive force is the voU. The ampere is
the strength of current which when passed through a solution of
silver nitrate under certain standard conditions will deposit 0.001118
Gm. of silver per second. The ohm is defined as the resistance
offered to an unvarying electric current by a column of mercury
106.3 cm. long and 1 sq. mm. in cross-section at 00. The voU
is the electromotive force necessary to force a current of one ampere
through a resistance of one ohm. The relationship between the
ampere, volt, and ohm is expressed in Ohm's law, viz.: The
strength of an electric current flowing through a conductor is directly
proportional to the difference of potential between the ends of the
conductor and inversely proportional to its resistance. If C represents the strength of the current in amperes, E the difference of
potential in volts, and R the resistance in ohms, Ohm's law may
be formulated as follows:
E
C = Ii
or, transposed,
E = OR
- The calculation of the amount of metal which will be deposited
during electrolysis in a given period of time is founded on Faraday's laws, which may be stated as follows:
305
306
ELECTROLYTIC METHODS
307
308
Ion
Metal
Zn++ ........... .
Fe++ ............. .
Sn++ ...... . .......
Pb++ ............ .
H+ ................
CU++ .. ....... .... .
Hg++ ..............
Ag+ ...............
OH- ..............
Zn
Fe
. Sn
Pb
. H 2 (Pt)
. Cu
. Hg
. Ag
. 02CPt)
1-................. . 12 (Pt)
Br- ... .
Cl- .... .
Br2(Pt)
C1 2 (Pt)
Decomposition
voltage
-0.7581 to 0.80
-0.441 to0.44
-0.136 to 0.14
- 0 . 122 to O. 12
0.0
toO.O
+0.3448 to 0.34
+0.7986 to 0.80
+0.7995 to 0.80
+0.3957 to 0.40
+0.5357 to 0.54
+ 1. 0659 to 1. 066
+ 1. 3594 to 1. 36
ELECTROLYTIC METHODS
309
voltage below 2.12 and above 0.27. The greater the difference is
between the decomposition voltages of two metallic ions the easier
it is to separate them by electrolysis. In general, it may be said,
that the decomposition voltages of two substances must differ
by at least 0.2 to 0.3 volt in order to permit their separation by
electrolysis.
Electrolytic methods of assay are not so simple as is implied
in the foregoing examples, since numerous factors complicate
conditions, viz., resistance of the solution, polarization, overvoltage, reactions at the electrodes, the nature of the solutions
used, the current density, the rate of stirring, the shape and size
310
device. A rheostat may be employed, but the ordinary slidingcontact resistance coil is convenient and satisfactory for most
purposes. The difference of potential between the electrodes
is measured by means of a voltmeter. The amount of current
flowing through the electrolytic circuit is measured by an
ammeter. The voltmeter and ammeter employed should be
designed for a limited range of measurement so that they may
be read easily and accurately.
The anode employed in electrolytic determinations usually
consists of a spiral, gauze, or disk of platinum of such construction
that it can be attached to a stirrer. Platinum is employed
FIG.
54.-Platinum
cathode.
dish
FIG. 55.-Platinum
foil cathode.
FIG. 56.-Platinum
gauze cathode.
ELECTROLYTIC METHODS
FIG.
311
FIG.
312
313
ELECTROLYTIC METHODS
Exercise 92
+ 80
4- -
The copper ions migrate to the cathode where each copper ion
gains two electrons and is reduced to metallic copper. The
sulfate ions migrate to the anode where they react with hydroxyl
ions from the water, forming molecular oxygen and sulfuric
acid:
+ 80 ----+280 + O
3-
+H
0--+H 280 4
314
ELECTROLYTIC METHODS
315
After stopping the current, detach the cathode cup and wash it
thoroughly with water, alcohol, and ether successively, dry it in
an electric oven or. air bath for 2 or 3 min. at 80 to 100C., allow
the cathode to cool in a desiccator, and weigh it. The operations
of drying and weighing should be performed as quickly as possible, since the copper is subject to oxidation upon exposure to air.
After weighing the cathodc with the copper deposit, dissolve the
deposit completely by treating it with two successive portions
of about 10 cc. of concentrated nitric acid mixed with about
10 cc. of water using gentle heat to effect solution. Wash the
electrode successively with distilled water, alcohol, and ether
and dry again at 80 to 100C., allow it to cool in a desiccatbr,
and weigh it again. The difference between the weight of the
cathode and the weight of the cathode with the copper deposit
is equal to the weight of copper deposited. The cathode may
be weighed before the electrolysis is started and again after the
deposition of the copper is complete, but this procedure leads to
a slight inaccuracy since the anode dissolves slightly during the
electrolysis and the dissolved platinum is plated out on the
cathode.
Calculate the percentage Cu, CUS04, and CuS04.5H 20 to
which the sample assayed corresponds.
Questions and Problems
1. Explain how oxidation and reduction are involved in the assay of copper
sulfate.
2. Why is the electrolyte acidulated with sulfuric acid?
3. Why is the solution of electrolyte stirred?
4. Why should the current not be stopped until the acid electrolyte has
been washed out of the cathode dish?
5. How many coulombs of electricity would be required to completely
deposit the copper from 0.6 Gm. of pure CuS04.5H 20?
Exercise 93
316
ELECTROLYTIC METHODS
317
+ Na+ + 2CN-
318
The mercury compounds insoluble in water for which electrolytic assays may be used, such as mercurous chloride, mercurous iodide, mercuric salicylate, and ammoniated mercury, are
electrolyzed from a solution of sodium sulfide, because mercury
sulfide is soluble in the presence of an excess of strong alkali
sulfide:
+ 2CH2COOH~2CH2COONa + H 2S
319
ELECTROLYTIC METHODS
Substance
U.S.P.
Copper sulfate ............
Copper sulfate, anhydrous
Mercury .................
Mercury, ammoniated .....
Mercury bichloride .......
Mercuric iodide, yellow ....
Mercuric oxide, yellow ....
Mercuric salicylate ........
Mercurous chloride, mild ..
Mercurous iodide, yellow ..
Mercury with chalk .......
Silver nitrate .............
Silver nitrate, toughened...
Zinc acetate ..............
Zinc chloride .............
Zinc oxide .. ,..............
.zinc sulfate ..............
Zinc sulfate, anhydrous ....
N.F.
Mercuric iodide, red .......
Mercuric oxide, red .......
Zinc phenolsulfonate ......
Amount
used,
grams
0.75 to 1.0
0.50toO.75
0.2 to 0.3
0.5 to 0.6
0.3 to 0.4
1.0 to 1.2
0.2 to 0.3
0.7 to 0.8
0.5 to 0.6
0.7 to 0.8
0.6 to 0.8
0.3 to 0.5
0.3 to 0.5
0.5
0.3
0.2
0.6
0.4
1.0 to 1.2
0.2 to 0.3
1.2
Amperage
used
Grams
equivalent
Voltage to 1 Gm.
used
of
deposited
metal
2.5
2.5
1.5 to
2 to
1 to
2 to
1.5 to
2 to
2 to
2 to
1.5 to
2"5
2.5
4 to
4 to
4 to
4 to
4 to
5 to
5 to
7 to
7 to
8 to
7 to
7 to
7 to
7 to
7 to
7 to
5 to
5 to
5 to
5 to
5 to
5 to
5 to
2
3
3
3
2
3
3
3
2
5
5
5
5
5
2 to 3
1.5 to 2
4 to 5
7
7
10
10
12
10
10
10
10
10
10
7
7
6
6
6
6
6
3.9281
2.5112
1.0000
1.2566
1.3535
2.2654
1.0798
1.1798
1.1768
1.6327
1.0000
1.5748
1.5748
3.3570
2.0849
1.2448
4.3988
2.4695
7 to 10
7 to 10
5 to 6
2.2654
1.0798
8.5011
'PART III
SPECIAL METHODS USED IN OFFICIAL
PHARMACEUTICAL ANALYSES
Quantitative analyses of crude drugs and of the products
derived from them are made to establish purity or to determine
the amount of therapeutically active constituents present for
the purpose of standardization. The special methods employed
in the analyses of this type may be classified as follows:
Chemical methods such as those employed in the determination
of ash, moisture, crude fiber, extractive obtained with different
solvents, the estimation of alkaloidal content, etc.
Physiological methods or those in which the effects upon
animals or animal tissues are measured and which are employed
in the absence of satisfactory chemical methods for standardization. The official drugs assayed by physiological methods are:
U.S.P. aconite, tincture of aconite, cod liver oil, non-qestearinated
cod liv:er oil, digitalis, digitalis powder, tincture of digitalis,
solution of epinephrine, solution of irradiated ergosterol, ergot,
fluidextract of ergot, extract of liver, solution of liver, purified
solution of liver, solution of parathyroid, solution of posterior
pituitary, stomach, and strophanthin and tests for the toxicity
and purity of arsphenamine, neoarsphenamine, and tryparsamide;
N.F. fluidextract of aconite, convallaria root, fluidextract of
convallaria root, ampuls of epinephrine hydrochloride, extract of
ergot, ampuls of posterior pituitary, fluidextract of squill, strophanthus, tincture of strophanthus, and suprarenal. Physiological methods require special apparatus for their performance
and a technique which is not chemical in nature; hence, a discussion of them does not fall within the scope of this text.
CHAPTER XX
324
325
ashless filter paper, incinerate the residue and filter paper until the ash is
white or nearly so, then add the filtrate, evaporate it to dryness and heat the
whole to a low redness. If a carbon-free ash cannot be obtained in this way,
cool the crucible, add 15 cc. of alcohol, break up the ash with a glass rod,
burn off the alcohol, and again heat the whole to a low redness. Finally
determine the weight of the ash. Calculate the percentage of total ash from
the weight of the drug taken."
326
3. Why should the incineration residue not be heated above a dull redness?
4. Name the important inorganic plant constituents which will not be
found in the ash.
6. What does the quantity of acid-insoluble ash in a drug indicate?
327
Substance
U.S.P.
Acacia ................ .
Acetanilid .......... .
Acetophenetidin. . . .. . ..
Acid. acetylsalicyhc.. ..
Acid. acetyltannic..
..
Acid. benzoic .. .
Acid, citric .. .......... .
Acid lactic.. . .
. ..... .
Acid. oleic... ... . . . .. ..
Acid. salicylic .......... .
Acid. tannic ........... .
Acid. tartaric .......... .
Acid. trichloroacetic ... .
Agar ................. .
Albumin tannate.
Aloe .................. .
Aloin .............. .
Aminopyrine . .......... .
Ammonium benzoate .. . .
Ammonium bromide . ... .
Ammonium carbonate.
Ammonium chloride ... .
Ammonium salicylate ... ,
Antipyrine ............ .
Asafoetida .......... '"
Aspidium ............. .
Belladonna leaf. ...... .
Belladonna root ... .
Benzoin, Sumatra ..
Benzoin, Siam .... .
Betanaphthol. ... .
Caffeine ........... .
Caffeine, citrated . .. .
Camphor ......... .
Cannabis ....... . .
Capsicum ......... .
Cardamom seed.
Caraway ..... .
Charcoal. activated ... .
Chloral hydrate ........ .
Chlorobutanol. " ... .
Chrysarobin ........... .
Clove ............... .
Cotton. purified ........ .
Creosote carbonate ..... .
Dextrose ... .
Total
ash.
per
cent
>Acidinsoluble
ash,
per
cent
4.0
0.5
0.05
0.05
0.05
0.3
0.05
0.05
0.12
0.10
0.05
0.5
0.05
0.05
1.0
0.3
4.0
0.5
0.1
0.05
0.05
0.05
0.1
0.05
0.1
15.0
3.0
3.0
4.0
o 05
1.0
0.5
0.05
0.1
0.05
5.0
1.25
5.0
1.5
4.0
0.05
0.1
0.25
0.75
0.2
0.1
0.1
Total
Substance
U.S.P.
Digitalis ............. "
Elaterin ............... .
Ephedrine ............. .
Ephedrine hydrochloride.
Ephedrine sulfate ...... .
Ethyl aminobenzoate .. .
Glucose .............. "
Glycerin .............. .
Glycyrrhiza ............ .
Glycyrrhiza. extract of .. .
Guaiacol. ............ .
Hyoscyamus . .......... .
Iodoform .............. .
Iodine .............. .
Lactose ...... ....... .
Menthol. ........... .
Mercuric chloride 300C.
Mercuric oxide, yellow .. .
Mercuric salicylate . .... .
Mercurous chloride . .... .
Mercurous iodide, yellow
Mercury .............. .
Mercury, ammoniated.
Mercury succinimide . .. .
Methenamine .......... .
Methylthionine chloride.
Myristica ............. .
Myrrh ................ .
Paraffin, chlorinated .... .
Petrolatum ............ .
Petrolatum. white ...... .
Phenacaine hydrochloride
Phenol. ............... .
Phenol. liquefied. . . .. ..
Phenolphthalein ....... .
Phenolsulfonphthalein .. .
Phenyl salicylate ....... .
Pi~ tar ............... .
Prepared chalk ........ .
Pyrogallol. ............ .
Quinidine sulfate ....... .
Qninine ............... .
Quinine ethyl carbonate.
Quinine and urea hydrochloride ............. .
Quinine bisulfate ..
ash,
per
cent
Acidinsolu
ble
ash.
per
cent
5.0
0.1
0.1
0.1
0.1
o1
0.5
0.007
2.5
8.0
0.1
12.0
0.2
0.05
0.1
0.05
0.1
0.2
0.2
0.1
0.2
0.02
0.2
0.1
0.05
1.0
0.5
4.0
0.1
0.05
0.05
0.1
0.05
0.05
0.05
0.2
0.05
0.25
2.0
0.1
0.1
0.1
0.2
0.05
0.05
328
Substance
Total
ash,
per
cent
U.S.P.
Quinine dihydrochloride.
Quinine suliate ......... .
Resin of podophyllum .. .
Resorcinol. ............ .
Resin ................. .
Saccharin, soluble ...... .
Santonin .............. .
Sarsaparilla, Mexican ... .
Senna ................. .
Serpentaria ............ .
Starch ................ .
Acidinsoluble
ash,
per
cent
0.05
0.05
1.5
0.05
0.05
0.5
0.1
4.0
3.0
10.0
0.5
Stramoni UIn .. . . . . . . . . . .
4.0
LIM1TS.-(Continued)
Substance
Total
ash,
per
cent
N.F.
Colocynth ............. .
Convallaria root ....... .
Coriander ............. .
Corpus luteum...... .... 6.0
Crocus.................
7.5
Cudbear. . . . . . . . .. .... 12.0
Damiana .............. .
Euonymus ............ .
Euphorbia ............. .
Fennel. ............... .
Gambir ............... .
Gamboge .............. .
0.1
Guaiacol carbonate......
Guarana .............. .
Humulus .............. .
Hydrastis ............. .
IchthammoI........ .... 0.5
Ipomoea .............. .
Iris .......... ......... .
10.0
4.0
0.5
5.0
3.0
3.0
1.0
0.5
6.0
due ................. .
1:::::
,.....
6.0
5.0
10.0
0.25
4.0
4.0
7.0
Pimenta .............. .
0.5
4.0
4.0
3.0
1.5
0.5
1.0
0.5
4.0
1.0
Kamala .............. .
1.5
2.5
4.0
3.0
6.0
6.0
1.5
Kola .................. .
Leptandra .......... , .. .
Lobelia ............... .
Lupulin ............... .
Mastic ................ .
Matricaria . ........... .
Mullein leaves ......... .
Ovary and ovarian resi-
10.0
0.5
2.5
AcidinsolubIe
ash,
per
cent
7.0
Pituitary, whole ....... . 7.0
Plantago seed .......... . 4.0
Poplar bud ............ .
Quassia ............... .
Resin. ipomoea . ..... , ..
0.5
Rose ................. .
Salvia ................ . 10.0
Sassafras .............. .
Sassafras pith .......... .
Strychnine ............ . 0.1
Suifonemethane ........ . 0.05
Suprarenal. ........... . 7.0
Taraxacum ............ .
Thyme ..... " ......... .
Triticum ....... ' ...... .
Ulmus ................ .
Viburnum prunifolium .. .
0.4
1.0
1.0
0.5
1.0
1.0
5.0
0.5
4.0
4.0
3.0
1.0
3.0
329
Substance
U.S.P.
Acetone ...... " ................ "
Acid, acetic .......................
Acid, diluted hydriodic .............
Acid, hydrochloric .................
Acid, nitric .......................
Acid, sulfuric .....................
Alcohol. .................... '" '"
Benzin, petroleum .................
Ether ............................
Ethyl oxide .......................
Water,
ammonia .......................
distilled ........................
distilled, sterilized ...............
orange flower ...................
rose, stronger ...................
N.F.
Antiseptic solution .................
Water ............................
Water, hamamelis .................
Water, redistilled ... , ..............
Amount
used, Gm.
or cc.
__Residue
dried at
c.
Official
requirement, Gm.
100
40
100
100
0.002
0.002
0.100
0.002
0.002
0.001
0.001
0.001
0.001
0.001
10
100
100
100
100
100
100
100
100
100
0.002
0.001
0.001
0.001
0.001
10
100
100
100
100
100
100
100
0.184
0.030
0.025
0.0005
50
20
5
10
30
2
40
50
50
50
100
100
Ignite
Ignite
Ignite
Ignite
330
331
Exercise 95
96
332
moisture-tube receiver calibrated to 0.1 cc. of the type illustrated (Fig. 59).
Clean the condenser and moisture tube with cleaning mixture (see page 5),
rinse with distilled water and then with alcohol, and dry them in an oven at
100C.
333
Substance
U.S.P.
Acacia .............. .
Acid acetyltannic. . . . .
Acid. tannic.. . . . . . . . .
Acriflavine. . . . . . . . . . .
Acr i II a vi ne, hydrochloride ............
Agar ............... .
Albumin tannate......
Aloe ................ .
Alum. exsiccated. . . . . .
Barbital. soluble. . . . . .
C~ffeine. .. . .. . . . . . . . .
Caffeine. citrated. . . . . .
Caffeine with sodium
benzoate. . . . . . . . . . .
Calcium iodobehenate.
Calcium lactate... . . . .
Cantharides. . . . . . . . . .
C ....ein. R...... . . . . . .
Codeine..............
Codeine sulfate. . . . . . .
Dextrose. . . . . . . . . . . . .
Digitalis ............ .
Digitali powdered ... .
Emetine hydrochloride
Ephedrine hydrochloride ................
Ephedrine sulfate. . . ..
Ergot ............... .
Ethylhydrocupreine
hydrochloride ......
Ethylmorphine hydrochloride.. .. . . . . . . . .
Fluorescin. soluble. . . .
Gentian ............. .
Glucose ............. .
Histamine phosphate ..
Iodoform ............ .
Magnesium oxide .... .
Magnesium sulfate ...
Merbaphen .......... .
Methylthionine chloride ..............
Morphine sulfate ..... .
Phenacaine hydrochloride .............. .
Phenobarbital. ...... .
Temperature,
C.
Moisture
limit,
per cent
15
100
100
100
H2S0,
100
200
100
80
80
80
100
120
100
100
80
100
105
100
H2S0.
H2S0,
3
12
7
7
16
6
10
10
1
9
5
5
2
25 to 30
10
10
6
12
10
8
5
8 t<i 16
2
2
8
H2S0,
100
105
90
100
H2S0.
Ignite
Ignite
100
10
5
10
21
1
1
10
45 to 52
2
"
16
110
130
12
105
140
7
7
Tern ..
Substance
perature,
C.
Moisture
limit,
per cent
U.S.P.
Phenolsulfonphthalein.
110
1
Potassium carbonate . .
180
15
Potassium citrate . ... .
150
3 to 6
Potassium iodide. " .. .
100
1.5
Potassium and sodium
tartrate .... ....... .
150
21 to 26
Quinidine sulfate. '" ..
120
5
Quinine ....... , ..... .
100
15
Quinine bisulfate ..... .
24
100
Quinine dihydrochloride .............. .
100
3
Quinine ethyl carbonate ............... . H2S0,
2
Quinine sulfate ....... .
100
16.2
Scopolamine hydrobromide .............. .
100
13
SoaP ............... .
llO
36
Soap. powdered ...... .
10
llO
Soap, 8oft ........... .
52
llO
Sodium acetate ...... .
120
36 to 41
Sodium biphosphate .. .
10 to 15
100
Sodium carbonate. ..
monohydra ted ..... .
10 to 15
110
10 to 13
Sodium citrate ... " .. .
150
Sodium iodide ....... .
120
7
Sodium phosphate ... .
43 to 50
110
Sodium phosphate, exsiccated ........... .
110
5
Sodium stearate .... .. .
110
5
Sodium sulfate ....... .
51 to 57
120
Sodium thiosulfate ... .
32 to 37
100
Starch .............. .
14
Strychnine sulfate .... .
100
11.5
Theobromine with sodium salicylate .. .. .
110
10
Theophylline ........ .
100
9.5
Theophylline with
ethylene diamine ... . H,SO,
4.5
Thyroid ............. .
100
6
Tryparsamide ....... .
110 2.5 to 3.5
Wool fat ............ .
100
0.5
Wool fat. hydrous .... .
25 to 30
100
N.F.
Acid. gallic .......... .
12
100
Aluminum sulfate .... .
200
45 to 49
Ammonium hypophosphite .............. H 2SO,
3
334
(Continued)
Temper-
Substance
ature,
DC.
Moisture
limit,
Substance
per cent
Temperature,
DC.
Moisture
limit.
per Qent
- - - - - - - - -------11--------N.F.
Ammonium iodide .. ..
Ammonium valerate,
acid ............ .
Arecoline hydrobromide ............ .
Brucine sulfate ...... .
Calcium glycerophosphate ............. .
Calcium hypophosphite ............. .
Calcium phosphate ... .
Carmine ............ .
Charcoal. purified animal. .............. .
Cholesterol. R ....... .
Cinchonidine sulfate .. .
Cinchonine sulfate ... .
Cinchophen ......... .
Corpus luteum ....... .
Cotarnine chloride, .. .
Ethyl carhamate ...
Ferric glycerophosphate ......... .
Ferric hypo phosphite ..
Hydrastine hydrochloride .............. .
Lithium benzoate .... .
Lithium c,,,bonate ... .
Li thi um citrate .... .. .
Lithium slllicyiate .... .
Manganese glycerophosphate......... .
Manganese hypophosphite ............. .
Mercuric iodide, red .. .
R.
= reagent.
H2S0.
110
H2S0.
H2S0.
100
13
130
10
H,SO.
3
4
200
100
100
100
100
100
100
H,SO.
H,SO.
110
H,SO.
25
12
2
12
5
2
6
1
3
5
3
H,SO.
100
100
150
26
100
110
H2S0.
120
= dried
10
2
1
N.F.
Mercuric o)(ide. red. .. H2S0,
Methyl-rosaniline. . .
110
Morphine hydrochloride. . . . . . . . . . . . . . .
Ovarian residue . ..... .
Ovary .............. .
Papaverine hydrochloride ...............
Pilocarpine hydrochloride ...............
Pituitary. anterior ... .
Pituitary, whole .. .
Potassium chloride.
Potassium guaiacolsulfonate... ....
Potas::dum hypophosphite...
. ...... .
Potassium thiocyanate
Quinine hYdrobromide.
Quinine hYdrochloride.
Quinine salicylate . ... .
Resin of ipomoea . ..... .
Resin of jalap .......
Sabal. .............. .
Salicin.. .. . .
. .... .
Sodium ",senate ..... .
Sodium hYllOphosphite.
Sodium sulfate ....... .
Sodium thiocyanate . . .
Sparteine sulfate ..... .
Strontium bromide ... .
Strontium salicylate .. .
Sulfonmethane ....... .
Suprarenal . ......... .
100
7.5
15
6
6
H2S0.
H,SO.
100
6
6
1
H,SO.
H,S04
Ii
Ii
llO
100
llO
5
10
100
1100
i
4
100
10 to 16
H2S04
"150
3
3
3
.;
H,SO.
100
llO
100
200
22
32
3
6
5
335
CHAPTER XXI
EXTRACTIVE AND CRUDE FIBER CONTENT
337
338
Substance
U.S.P.
Capsicum ............ .
Cinnamon ..............
Clove ............... , ..
Ginger .................
Ginger, fluidextract of ...
Linseed .............. , ..
Myristica ......... , .....
12
.
.
.
.
.
.
2
15
4.5
4.5W/V
20
30
25
N.F.
.
.
.
.
.
.
.
22
0.5
10
70
60
97
1.0
3.5
339
hours and weigh the total ether extract. Now heat the extract gradually
up to 110C. until the weight becomes constant; the loss in weight during
the heating represents the,volatile portion of the extract."
Object.-Assay of Benzoin.
Materials Required.-2 Gm. of benzoin.
100 cc. of alcohol.
Procedure.-l. "Place about 2 Gm. of Benzoin, accurately weighed, in a
tared extraction thimble and about 0.1 Gm. of sodium hydroxide in the
receiving flask of the extraction apparatus and extra-ct with -.alcohol in a
Soxhlet apparatus or other suitable extraction apparatus for five hours, or
until completely extracted."
340
method, page 331, calculate the weight of moisture in the Benzoin and subtract this weight of moisture from the original weight of the Benzoin taken
for the assay. The difference between this result and the weight of the
residue determined above represents the alcohol-soluble extractive."
Substance
Alcohol used,
per cent
Extractive,
per cent
U.S.P.
Asafoetida ..............
Benzoin, Sumatra ........
Benzoin, Siam ...........
Bismuth and potassium
tartrate ...............
Bismuth subgallate .... '"
Kino ...................
Myrrh ..................
Rhubarb ................
94
94
94
50
75
90,
94
94
94
94
49
(n.m.t.) 0.5
(n.m.t.) 0.5
73
94
94
94
94
95
95
49
25
65
60
85
75
80
40
12
60
30
30
N.F.
341
Water-soluble Extractive and Water-insoluble Residue.The determination of the water-soluble extractive content is
applied to those drugs one or more of the most important constituents of which are soluble in water, e.g., aloe, gambir, anet
kino. The determination is performed in the same way as the
determination '~f the alcohol-soluble extractive. The determination of the amount of water-insoluble residue is used as a
test for the purity of some substances. Thus, it is required
that acacia yield not more than 1 per cent, aloin yield not more
than 1.5 per cent, acetyltannic acid yield not more than 6 per
cent, and acriflavine yield not more than 0.5 per cent of waterinsoluble residue.
Exercise 99
Object.-Assay of Aloe.
Materials Required.-2 Gm. of aloe.
Procedure.-Proceed as directed in the assay of benzoin, Exercise 97,
using distilled water instead of alcohol as the solvent.
Water-soluble
Extractive,
Per Cent
Substance
U.S.P.
Aloe .........................................., ....
Gentian ..........................................
Ginger ...........................................
Kino .............................................
50
30
12
80
N.F.
Gambir ........................................... 70
342
343
By diluting exactly 51 cc. of normal sulfuric acid or an equivalent amount of a standard acid of known normality to 200 cc.
at 25C., 200 cc. of 1.25 per cent sulfuric acid may conveniently
be prepared. The prepared acid solution should be measured
and heated to boiling before it is added to the drug. When
the acid solution is added to the powdered, ether-exhausted
drug contained in a cold flask, the solution is cooled below its
boiling point. The mixture should be heated rapidly to bring
it to the boiling point again, and thereafter the flame should be
cut down to the minimum required to maintain slow, steady
boiling. Since the amount of material dissolved by the acid
solution is partly dependent upon the length of time that the
latter is heated in contact with the sample, it is important that
the mixture should be boiled exactly 30 min., the time period
being taken from the time the mixture starts to boil and not
from the time the hot acid solution is added. The flask should
be rotated gently from time to time while the mixture is being
boiled to bring particles of the drug which adhere to the walls
of the flask into contact with the acid. A current of air, passed
into and beneath the surface of the mixture, through a capillary
tube, will frequently prevent excessive frothing. The acidinsoluble residue is collected on a filter and washed until free of
acid, since the latter, if present, would neutralize~some of and,
consequently, reduce the concentration of the alkali used in the
next step of the procedure.
3. "Rinse the residue back into"the flask with 200 cc. of boiling sodium
hydroxide solution, adjusted to exactly 1.25 per cent by titration and free
from sodium carbonate. Again heat the mixture to boiling and continue
the boiling exactly 30 min. under the reflux condenser as described under
the treatment with acid, then rapidly filter through a tared filter, wash the
residue with boiling distilled water until the last washing is neutral, dry it at
110C. until of constant weight, and note the weight."
344
CHAPTER XXII
346
347
benzoic acid in the free state, an acid value of less than 112 would
indicate that the acid content of the balsam was low and thll.t it
was of inferior quality or adulterated. On the other hand, an
acid value greater than 168 would indicate adulteration with
some substance having high acid value, such as certain resins.
Exercise 101
348
Substance
Amount
used,
Gm.
Alkali
used
Official
rtquircment,
cid value
U.S.P.
Acid, oleic ................
Copaiba ..................
Peruvian balsam ..........
Rosin ...................
Soap, hard (acids) .........
Soap, soft (acids) ..........
Storax, American ..........
Storax, Levant ............
Tolu balsam ........ I .
10
2
1
10
10
10
1
1
1
N.F.
Mastic ...................
Resin of ipomoea ..........
10
2
0.1 N NaOH
0.5NKOH
0.5 N NaOH
0.1 N NaOH
0.1 N NaOH
0.1 N NaOH
0.5 N NaOH
0.5 N NaOH
0.5NKOH
(alcoholic)
.0.5 NKOH
(alcoholic)
0.5NKOH
(alcoholic)
188 to 200
28 to 95
56 to 84
Not less than 150
185 to 205
190 to 205
38 to 85
56 to 85
112 to 168
0.1 N NaOH
0.5 NKOH
17 to 23
18 to 24
349
o. If a 2 Gm. sample of cod liver oil required 4.5 cc. of 0.02 N NaOH in
the titration of the free fatty acids, would the oil conform to the official
purity requirement? What would be the acid number of the oil?
6. Calculate the minimum and maximum acid values permitted under
the tests for purity of chaulmoogra oil.
In addition to the listed substances for which definite acid
value limits are given in the official standards, there are a number
of substances for which the maximum content of free fatty acids
is fixed by the volume of the standard alkali solution required
in their titration; e.g., 2 Gm. of cod liver oil must require not
more than 1 ee. of 0.1 N NaOH, and 1 Gm. of prepared suet
should not require more than 0.6 cc. of 0.1 N NaOH to neutralize
the free fatty acids.
Saponification Value.-The saponification value, saponification
number, or Koettsdorfer number, as it is sometimes called from
the originator of the process, is defined as the number of mt'lligrams
of potassium hydroxide required to neutralize the free acids and
saponify the esters contained in 1 Gm. of oil, fat, wax, or other
substance of similar composition. This value represents the
amount of potassium hydroxide, expressed in tenths of 1 per cent,
required to neutralize the total free and combined acids in 1 Gm.
of the substance, or, in other words, it is ten times the percentage
of potassium hydroxide required to neutralize all of the acids
contained in the sample afte.r saponification. Since the natural
fats and oils consist of mixtures of glyceryl esters of the higher
acids, their saponification values do not differ greatly. The
determination of the saponification value, however, serves to aid
in the detection or" the presence of the glycerides of acids containing less than 16 or more than 18 carbon atoms, since the value
of this constant is inversely proportional to the mean molecular
weights of the acids present. In some. cases, it may a,_lso indicate
adulteration of the sample with ul,lsaponifiable matter, such as
mineral oil.
Exercise 102
350
"If the oil has been saturated with carbon dioxide for the purpose of preservation, it should be exposed in a shallow dish in a vacuum desiccator for
twenty-four hours before the portions are weighed for this determination."
Procedure.-l. Place from 1.5 to 2 Gm. of the sample, accurately weighed,
in a flask of from 200 to 250 cc. capacity, and add to it exactly 25 cc. of
alcoholic 0.5 N potassium hydroxide. rnsert into the neck of the flask, by
means of a perforated stopper, a glass tube from 70 to 80 cm. in length and
from 5 to 8 mm. in diameter, and heat the flask on a water bath for 72' hr.,
frequently rotating the contents.
CSH6(C17HssC02)S
glyceryl oleate
potassium oleate
351
The approximate amount of alkali consumed in the saponification of the oil is found by subtracting the volume of 0.5 N ReI
used in the residual titration from the volume of 0.5 N alcoholic
KOR originally added. Sulfuric acid should not be substituted
for hydrochloric acid, since potassium sulfate would be precipitated from the alcoholic solution and this would interfere with
the observation of the end point.
3. Make a blank test at the same time, using exactly the same amount
of alcoholic 0.5 N potassium hydroxide. The difference in the number o~
cubic centimeters of 0.5 N hydrochloric acid consumed in the actual test
and the blank, multiplied by 28.06 and divided by the weight of the sample
taken, gives the saponification value.
or to 2
~6i~~00 =
0.02806 Gm.
~OR,
= 192.2 mg. KOH required to saponify the esters and neutralize the free fatty acids in 1 Gm. of the sample.
352
Saponification
value
Amount
us~sl,
Substance
Gm.
o
U.S.P.
Balsam of Peru ................
Castor oiL ....................
Chaulmoogra oil. .......... ...
Cod liver oil. ..................
Corn oil. .....................
Cottonseed oil. ................
Ethyl chaulmoograte ...........
Expressed oil of almond .........
Lard .........................
Linseed oil. ......... , ........
Oil of thedbroma ...............
Olive oil. ............
Prepared suet .................
Storax ........................
Tolu balsam ...................
N.F.
Croton oil ................... ~ .
Resin of ipomoea ..............
Sesame oil. ...................
o
3
1.5 to 2
1.5 to 2
1.5 to 2
1.5to2
1.5to2
1.5to2
1.5 to 2
1.5to2
1.5to2
1.5to2
1.5to2
1.5to2
1.5 to 2
1
235 to
179 to
196 to
180 to
188 to
190 to
190 to
191 to
195 to
187 to
188 to
190 to
193 to
160 to
154 to
1.5 to 2
1.5to2
1
200 to 215
170 to 190
188 to 193
238
185
213
192
193
198
196
200
203
195
195
195
200
200
220
353
354
355
the ether just to dryness on a water bath, and dry the residue for
30 min. at 100C. Cool the beaker in a desiccator for 30 min.,
and weigh the residue of unsaponifiable matter.
The Pharmacopoeia requires that both cod liver oil and linseed
oil should not contain more than 1.5 per cent and that corn oil
should contain not more than 2 per cent of unsaponifiable matter.
Iodine Value.-The iodine value, or number, is the number of
grams of iodine absorbed by 100 Gm. of oil, jat, wax, or other substance under specified conditions. This value is a quantitative
measure of the proportion of unsaturated fatty acids present,
both free and combined as esters, which have the property of
absorbing iodine.
The determination of the iodine number of fats and oils is
important, since it serves to characterize them and to indicate
whether they are pure or admixtures. The so-called drying oils,
such as linseed oil, and the fish oils, such as cod liver oil, have
very high iodine numbers, usually above 120, since they contain
a large proportion of unsaturated fatty acids; the non-drying oils,
such as olive oil and almond oil, have relatively low iodine
numbers, below 100; and the semidrying oils, such as cottonseed
oil and sesame oil, have intermediate iodine values, that is,
between 100 and 120. In the case of the animal fats, the iodine
number is not very high, usually being less than 90. The determination of the iodine number, therefore, not only serves as an
aid to the identification of known oils, but it also serves to indicate in a definite manner the class to which an unknown fat or
oil belongs. Furthermore, when the iodine number is considered
in conjunction with the saponification value of a fat or oil, it
serves as a means of detecting adulteration, and frequently it
indicates the nature of the adulterant; e.g., olive oil might be
adulterated with cottonseed oil without changing -the saponification value appreciably, but the iodine number of the olive oil
would be increased. Again, castor oil might be adulterated
with olive oil without changing the iodine number greatly, but
the saponification value of the castor oil would be increased.
Several methods have been developed for the determination
of the iodine number of fats and oils. These methods are
generally designated by the name of their originators, as, for
example, the Hubl, Hanus, and Wijs methods. The method
356
~~5
ing 980 cc. of iodine test solution would contain 980 X 0.01238 =
12.13 Gm. of iodine. Since 126.92 Gm. of iodine-is equivalent to
79.92 Gm. of bromine, the quantity of bromine equivalent to
the iodine contained in the solution may be calculated.
X :12.13 ::79.92 :126.92
X = 7.64 Gm. bromine
357
358
Upon the addition of the potassium iodide solution, the iodine bromide reacts with the K1,
liberating iodine until all of the bromine is used up:
K1
+ 1Br~KBr + 12
2Na 2S20a
+ 12~2NaI + Na2S406
3. "Carry out a blank test at the same time .with the same quantities of
chloroform and iodobromide solution, allowing it to stand for the same length
of time and titrating as directed. The difference in the number of cubic
centimeters of thiosulfate consumed by the blank test and the actual test,
multiplied by 1,269 and divided by the weight of sample taken gives the
Iodine Value.
"NOTE.-If the number of cubic centimeters of tenth-normal sodium
thiosulfate consumed in the actual test is less than 60 per cent of the quantity
consumed in the blank test, the determination must be repeated, using a
smaller amount of the material being assayed."
The blank test, when carried out under the same conditions
as the actual test, corrects for the presence of impurities in the
reagents, changes in volume at different temperatures, etc.,
and makes it unnecessary to know the exact normality Of the
iodobromide test solution. The blank test should be carried out
359
~6i9000
, =
Substance
Iodine Number,
Official Requirement
U.S.P.
Acid, oleic. . . . . . . . . . .
. ......... .
85 to 95
Acid, stearic ...... " . . .. . ....... . Not more than 4
Castor oiL.... . .. . .. . ............ .
83 to 88
Chaulmoogra oil. .................... .
93 to 104
Cod liver oil. ............... , . .. ..
145 to 180
128 to 180
Cod liver oil, non-destearinated. .. . .. .
Corn oiL.... . . . . . . . . . .. .... . ..... .
112 to 128
105 to 114
Cottonseed oil. . . . . .. . .............. .
Ethyl chaulmoograte ................. .
90 to 100
Expressed oil of almond .............. .
93 to 100
Lard .................... .
46 to 70
Linseed oil. . . . . . . . . . . . . . . . .. . ...... . Not less than 170
Oil of theobroma. . . . . . .. . .......... .
35 to 40
Olive oil. ........................... .
79 to 88
Prepared suet. . . . . . .. . ............. .
33 to 48
Soap, hard (acids from) .......-;-....... .
83 to 92
Soap, soft (acids from) ............... . Not less than 170
Wool fat ........................... .
18 to 36
N.F.
Croton oil. ......................... .
104 to 110
Oil of sesame ........................ .
103 to 115
360
CHAPTER XXIII
ASSAY OF VOLATILE OILS
Volatile oils, also known as ethereal oils or essential oils and, in
some cases, as essences, are generally complex products composed
of mixtures of compounds of widely variant chemical characteristics. The most important chemical components of the
official volatile oils are:
1. Hydrocarbons, occasionally of the aliphatic series, such as
heptane, myrcene, and various paraffins; but more often of the
aromatic series, e.g., pinene, camphene, limonene, bornylene,
fenchene, dipentene, sylvestrene, and phellandrene.
2. Alcohols, present both in the free state and in combination
with acids as esters. The alcohols most generally found in the
official volatile oils are linalool, geraniol, citronellol, terpineol,
borneol, menthol, and santalol.
3. Aldehydes, such as benzaldehyde, cinnamic aldehyde, salicyl
aldehyde, citral, and citronellal.
4. Ketones, the most important being camphor, carvone,
fenchone, thujone, and menthone.
)
5. Phenols, e.g., anethol, eugenol, carvacrol, safrol, chavicol,
and thymol.
6. Acids, sometimes present in the free state in small quantities, those occurring most commonly being acetic, propionic,
butyric, valerie, benzoic, cinnamic, and hydn>cyanic acids; but
more often occurring in combination with the alcohols mentioned under 2 as esters, e.g., linalyl acetate, bornyl acetate, and
menthyl acetate.
I
7. Sulfur compounds, such as\. the allyl thiocyanate, found in
mustard oil.
The analysis of volatile oils for the purposes of determining
their purity and value is based on the measurement of certain
physical characteristics, on the quantitative estimation of certain
components as alcohols, phenols, esters, and aldehydes, and on
361
362
the qualitative tests for the various substances which are commonly employed as adulterants. Only the official quantitative
procedures will be discussed here.
Methods of General Application.-The purity and quality of
volatile oils may be judged to some extent by their appearance,
odor, color, etc.; but the information gained from the determination of the specific gravity, rotatory power, refractive index,
solidifying point, solubility, and behavior on distillation is of
much greater importance.
Specific Gravity.-The specific gravity of a volatile oil may be
determined with the Westphal balance or pycnometer, the
latter being the more accurate method of the two, and expressed
as the ratio of the weight of the volume of oil to that of an equal
volume of pure water when both are determined at 25C. (see
page 217).
The specific gravities of the official volatile oils vary approximately between 0.84 and 1.2. Those oils which are lighter
than water are usually rich in hydrocarbons, alcohols, esters,
aldehydes, and ketones, such as oil of orange, caraway, coriander,
lemon, turpentine, and rosemary. Oils the spt;;_cific gravities of
which approach or exceed 1.0 usually contain chiefly phenols,
phenolic derivatives, or certain esters, e.g., oil of anise'lcinnamon,
clove, sassafras, and mustard.
The specific gravity of any volatile oil is not absolutely constant, since it is influenced by such factors as the matl,J.rity of the
plant from w!ich the oil is obtained, as well as the method of
preparation, purification, and age of the oil.
Rotatory Power.-The rotatory power of a volatile oil is
generally measured with a Laurent half-shadow polarimeter,
according to the procedure described on page 247, using sodium
light and a tube 10 cJ?1. long, but for highly colored oils, tubes 5
or even 2.5 cm. long may be used. The observation of the
optical activities of the official essential oils should be made at
25C. Slight deviations from this temperature do not greatly
affect the rotatory power of a volatile oil, except in the case of oil
of lemon and oil of orange.
The rotatory power of some of the volatile oils varies within
relatively wide limits. This determination should never be
omitted in their examination, however, since it frequently serves
363
as a valuable means of detecting adulteration with inactive substances, such as alcohol t or with substances of different rotatory
power from that of the oil being examined, e.g., oil of lemon
(+57 to +64) adulterated with oil of turpentine (about +25 to
-40).
Refractive Index.-The refractive index of a volatile oil is
most commonly determined by means of an Abbe refractometer,
as described on page 240. The measurement of the refractive
indices of all of the official volatile oils should be performed at
20C. The index of refraction does not vary greatly with
different official volatile oils, the values being between about
1.46 and 1.61 at 20C. In some cases, this determination may,
however, serve for the detection of extraneous matter.
Congealing Point.-The congealing point of a volatile oil is
determined by the method described on page 231. Most essential oils solidify only at low temperatures, consequently in
practice, this determination is carried out with only a few oils,
such as oil of anise and oil of fennel, which contain large amounts
of the readily crystallizable constituent anethol. The higher
the congealing point of these oils the more they are valued.
An abnormally low congealing point of an essential oil indicates
the partial removal of the characteristic constituent for which
the oil is valued or the addition of extraneous matter, such as
alcohol.
Distilling Point.-The distilling point of a volatile oil is
determined by the general method described on page 234.
Volatile oils which are composed of mixtures of hydrocarbons,
alcohols, esters, etc., do not have a fixed boiling point but boil
between certain limits of temperature, frequently separated
widely. Consequently, the official standards usually designate
the temperature or range of temperature at which a definite
percentage of the oil distils; e.g., 90 per cent of oil of turpentine
should distil between 154 and 170C., and less than 10 per cent of
oil of dwarf pine needles should aistil below 1650.
Fractional Distillation.-Fractional distillation is resorted to
occasionally in the official tests for purity of volatile oils. It
serves either to' separate the various components of volatile oils
or to detect adulteration. Thus, alcohol and petroleum ether,
both of which boil below 1000., may be separated and identified
364
in this way. The addition of oil of turpentine and other adulterants may be detected by collecting various fractions of the oil
and determining the rotary power and refractive index of
each fraction; e.g., see Oil of Orange, U.S.P., page 250.
Solubility.-The volatile oils are generally soluble in organic
solvents, such as absolute alcohol, ether, chloroform, benzene,
carbon disulfide, etc. They dissolve more or less readily in
dilute alcohol according to the nature of their components. Oils
containing a large percentage of oxygenated substances often
produce turbid solutions with petroleum ether or carbon disulfide due to the separation of water, small quantities of which
are dissolved in such oils.
Practically all of the volatile oils exhibit almost constant
solubility in 90, 80, or 70 per cent alcohol. Consequently, the
test of the solubility of a volatile oil in dilute alcohol frequently
gives valuable data relative to its purity, since the commonly
used adulterants, oil of turpentine, petroleum oils, and fatty
oils, are but slightly soluble in 80 or 70 per cent alcohol.
Assay for Ester Content.-A number of the official volatile
oils are evaluated on the basis of their ester GOntent. The esters
found are mostly the acetates of alcohols of the formula C lOH 170H,
e.g., borneol, geraniol, linalool, and terpineol; C 1QH 190H, such
as menthol or citronellol; or C 15H 2SOH, e.g., santalol. When
these esters are refiuxed with alcoholic potassium hydroxide,
they are saponified and yield the free alcohol and the potassium
salt corresponding to the acid component of the ester.
The number of milligrams of KOH required to saponify 1 Gm.
of the oil represents the ester value or ester number of the oil.
The ester number for any given oil may be subject to considerable
variation, but the minimum requirement set by the official
standards must be complied with when the oil is represented as a
product conforming to the U.S.P. or N.F. standards. The
determination of the total esters when taken in conjunction with
the official tests for purity serves to detect adulteration
and to establish the quality of those oils valued for their ester
content.
The ester values of oils which contain appreciable amounts of
aldehydes or phenols cannot be estimated accurately by saponification with an alkali, since variable amounts of the latter are
365
The potassium hydroxide converts any acids present into nonvolatile salts and causes the polymerization of aldehydes. The
lead acetate is decomposed by the KOH with the formation of
lead oxide and potassium acetate. The lead forms insoluble and
non-volatile compounds with any sulfur compounds present.
The lead oxide carries down the polymerized aldehydes when it
is precipitated so that it is easy to decant the clear supernatant
liquid.
2. "Dissolve about 35 Gm. ot potassium hydroxide in 20 cc. of distilled
water and add sufficient aldehyde-free alcohol to make 1000 cc. Allow the
solution to stand in a tightly-stoppered bottle (using either glass or rubber
stopper) for twenty-four hours. Then quickly decant the clear supernatant liquid into a bottle provided with a well-fitting rubber-stopper and
standardize as follows:"
366
Calculate the
'
2. "Allow the mixture to cool, disconnect the flask from the condenser,
and titrate the excess of alkali with half-normal sulfuric acid, using 10
367
~8i~0400
This
368
Amount Equivalent of
used,
1 cc. of 0.5 N
Gm.
KOH,Gm.
Official requirement,
per cent
U.S.P.
Methyl salicylate ......
0.07603
Methyl salicylate
C.H4(OH)CO.CH. = 98
10
0.09811
0.09811
10
0.09912
10
0.09811
Bornyl acetate
CloHI7C.H.02 =
Linalyl acetate
C IOH I7C.H.O. =
Menthyl acetate
CloHuC.HaO. =
Bornyl acetate
C IOH I7C.HaO. =
N.F.
Oil of bergamot .......
0.09808
5
30
5
2.5
Linalyl acetate
C1oH'7C.H.O. = 36
Exercise 106
369
C-CH3
OH+O
'\,
-O-C-CH 3 + CHaCOOH
G-CH s
,f'
.
6
-OH
0
~
+ H0-C--CHs-
'\,
O-G-CHs + HOH
2. "When the liquids have completely separated, reject the aqueous layer,
and wash the remaining oil with successive portions of sodium carbonate
T.S., diluted with an equal volume of distilled water, until the washing is
alkaline to 2 drops of phenolphthalein T.S. Dry the resulting Oil with
anhydrous sodium sulfate (prepared by drying sodium sulfate to constant
weight at 110C. and powdering), and filter it."
370
The oil is washed with sodium carbonate test solution (12.5 Gm.
of Na2,C0 3 .H2,O ,in sufficient distilled water to make 100 ce.) to
neutralize the excess acetic acid. The washed oil is then dried
over anhydrous sodium sulfate to remove the small amounts of
alkaline sodium carbonate solution which it contains.
3. "Transfer 5 cc. of the dry acetylilled oil to a tared, 100-cc. Erlenmeyer
flask, note its exact weight, add 50 ce. of half-normal alcoholic potassium
hydroxide, connect the flask with a reflux condenser, and boil the mixture
on a water bath for one hour."
The 0.5 N KOH saponifies the menthyl acetate, forming menthol and potassium acetate in the s~me manner as in the assay for
total esters. The liberated menthol dissolves in the alcoholic
solution.
4. "Allow the mixture to" cool, disconnect the flask from the condenser,
and titrate the excess of alkali with half-normal sulfuric acid, using 10 drops
of phenolphthalein T.S. as the indicator. Calculate the per cent of menthol
by the following formula:
Per cent of total menthol in the Oil tested
!(~ ~8~~21)
_x [1 - (E X 0.0021)].
371
198.17 (moleculal' weight of menthyl acetate) - 156.16 (molecular weight of menthol) = 42.01 (molecular weight of the acetyl
radical). Therefore, 1,000 cc. of N KOH is equivalent to 42.03
Gm. of acetyl radical, and 1 cc. of 0.5 N KOB is equivalent to
2 X 4;,000
(A X 0.021), therefore,
(E X 0.0021)].
Problem~
1. Having determined the ester value and 'the percentage of total borneol
present in oil of rosemary, how could the percentage of free borneol be
found? Give an example.
;372
2. Write the reactions which take place in the assay of oil of rosemary for
total borneol.
3. If oil of peppermint containing 7.2 per cent of total esters is found to
contain 51.5 per cent of total menthol (uncorrected), what change in the
result would the correction 1 - (E X 0.0021) cause? Is this correction
important?
TABLE LVI.-OFFICIAL VOLATILE
OILS ASSAYED
FOR THEIR
ALCOHOL
CONTENT
Oil
Amount of
acetylized
oil used,
Gm.
Equivalent
of 1 cc. of
0.5 N KOH,
Gm,
Correction factor
U.S.P.
Oil of peppermint ...
0.07808
1 - (E X 0.0021)
0.0771
1 - (E X 0.0021)
0.1101
None
Menthol
ClOH"OH =50
Borneol
ClOH170H = 10
Santalol
C"H"OH = 90
/'
CR CH-C
'"
NaO
0
'" /'
+2
SH
/~
Na
0
+ 2NaOH
373
The sulfite addition product dissolves in water leaving the nonaldehyde constituents as a water-insoluble layer. The volume
of this water-insoluble layer is then measured in a cassia flask,
(Fig. 63).
The cassia flask is a glass flask of about 100 cc. capacity with a
long, narrow neck graduated to 10 cc. in 0.1 cc. divisions. In the
assay for aldehydes and ketones by the sulfite method or bisulfite method, the portion of the oil which does not react to form
a water-soluble addition product rises to the surface, and when
the flask is filled, this oily layer rises into the graduated neck
of the cassia flask where its volume can be measured. The volume of the residual oily layer
subtracted from the volume of the sample of oil used
represents the volume of the aldehyde constituents
r
which formed a water-soluble addition product with
the sulfite.
I:
Those volatile oils which contain aldehydes in
very small amounts, such as oil of lemon, or which
contain other constituents that form water-soluble
addition products with sodium sulfite and bisulfite
cannot be assayed accurately by this method. In FIG. 63.Cassia
these cases, the aldehydes are generally determined flask.
by the phenylhydrazine method (see assay of
benzaldehyde, N.F.) or by the hydroxylamine method described
in the following exercise.
Exercise 107
374
375
Oil
Amount
used
Official requirement,
per cent
Method
U.S.P.
Oil of bitter almond ......... 1 Gm. Hydroxylamine
Oil of cinnamon .. 10 cc.
Sulfite
Benzaldehyde = 95
Cinnamic aldehyde = 80
N.F.
Benzaldehyde ....
Carvone, the principal ketone present in the oil, reacts with the
sodium sulfite, forming a water-soluble addition product as
follows:
376
ONa
()<sE~
) ~
ONa
The presence ,of free alkali in the aqueous layer renders other
components of the oil, such as phenols, water-soluble and also
tends to reverse the addition reaction. To pt:event this the
sodium hydroxide is neutralized by the addition of sodium acid
sulfite:
2. "When no coloration appears upon adding a few more drops of phenolphthalein T.S. and heating for 15 minutes, cool the mixture to room temperature, and, when the liquids have separated completely, add sufficient
sodium sulfite solution to raise the lower limit of the oily layer within the
graduated portion of the neck of the flask. Note the volume of the residual
oily liquid. This volume does not exceed 5 cc., indicating the presence in
the Oil of not less than 50 per cent, by volume, of carvone."
The difference between the volume of oil used as the sample and
the volume of the oily layer which remains insoluble represents
the carvone which dissolved in the aqueous layer. If drops of
oil adhere to the walls of the fiask,-they may be made to rise into
the neck by gently tapping and rotating it. If the residual
liquid measures 4.5 cc., the percentage of carvone by volume in
the oil would be 10
~O 4.5
The only other official oil evaluated for its ketone content is oil
of spearmint. It is assayed in exactly'the same way as is oil of
377
-CH 2-CH
+KOH~
CH 2
-OK
O-OCH3
-CH2-CH
+HOH
CH2
378
~t
Amount
used, cc.
Alkali
used
Official requirement,
per cent
10
KOH
Eugenol C lOH ,2 0 2 = 82
myrcia ..............
pimenta. , ..........
thyme ... , ..........
10
10
10
KOH
KOH
KOH
Phenols = 50 to 60
Eugenol,C ,o H 120 2 = 65
Phenols = 20
Oil
U.S.P.
Oil of
N.F.
Oil of
Oil of
Oil of
Assay for Hydrocyanic Acid Content.-Only one official volatile oil is assayed for its hydrocyanic acid content, namely, oil of
bitter almond.
379
Exercise 110
+ 2NaOH~Mg(OH)2 + Na 2S04
20
-C-OH
"C=N
+ Mg(OH),-.
H
/
C~
0
+ Mg(CN)2 + 2HOH
380
+ 2AgNOa~Ag2Cr04 + 2KNOa
381
The ascaridol in the oil dissolves in the 60 per cent acetic acid.
The exact nature of the reaction that occurs is not known, but it
may be represented as follows:
{D
I
~
I-O-C-CHs
+ 2CH'COOH~O + 2HOH + 0,
382
383
N-C sH5
~C
+ 2NH NOs + H 20
4
+ 3NH s + 2AgNOs~Ag2S +
CNNHCsH.
+ 2NH4NOs
NH4SCN~AgSCN
NH4NOs
6NH4SCN~2Fe(SCN)3
4(NH4)2S04
Each cubic centimeter of 0.1 N AgN0 3 consumed in the reaction with the hydrogen sulfide is equiyalent to 10 X 91~OI;O X 2
0.004947 Gm. allyl isothiocyanate, where 99.13 is the molecular
weight of the latter and 2 is its hydrogen equivalent. In calculating the percentage of aliyl isothiocyanate in the sample, it should
be noted that an aliquot portion of the filtrate corresponding to
one-half of the sample taken is represented in the titration.
384
1. Why is nitric scid used in the titration of the excess AgNO a with
KCNS?
2. Explain each step of the procedure given in the U.S.P. for the sssay
of black mustard.
3. Write equations for all of the reactions that take place in problem 2.
385
Spirit
Amount
used,
cc.
5
5
10
2
5
~5
Factor
4.2
4.2
2.2
10.5
4.2
4.2
Official
requirement,
per cent
9 to
9 to
4 to
25 to
9 to
9 to
11 V/V
11 V/V
6V/V
30V/V
11 V/V
llV/V
CHAPTER XXIV
ALKALOIDAL ASSAYING ..
Proximate Assays.-Alkaloidal assays are commonly referred
to as proximate assays. When such substances as the alkaloids
and glycosides were first isolated from. vegetable matter, they
were regarded as plant principles which still retained their
vegetable character, which entered immediately into the composition of the plant, and which had not been: altered in composition.
Consequently, they were called proximate principles is opposed
to the ultimate principles, such as water, carbon, acetic acid, and
methyl alcohol which had previously been obtained more ot less
from all plant products by the methods of pyroanalysis (destructive distillation).
General Principles.-The alkaloidal drugs and preparations
derived from them constitute a relatively large1>roportion of the
official substances which are employed frequently in modern
therapy. As a class of medicinal agents, they ar~ ch~racterized
by their high potency. A slight deficiency of alkaloid in a
preparation may cause a marked decrease in physiological
effect; on the other hand, a slight excess may cause toxic effects
when the preparation is administered. It therefore follows that
the accurate estimation of the quantity of alkaloids present in a
medicinal substance is an important subdivision of pharmaceutical analysis.
"The assay of alkaloidal drugs and preparations is generally
performed for purposes of standardization, proof of purity,
commercial evaluation, or pharmaco-Iegal purposes. Methods of
various types have been developed for the quantitative estimation.
of these principles, e.g., gravimetric, volumetric, colorimetric,
potentiometric, and physiological. The official assays are limited
to the gravimetric, volumetric, and physiological methods, only
the first two of which come within the scope of this work.
The amounts of alkaloids which occur in crude drugs are subject
to considerable variation in different samples of the same drug.
386
ALKALOIDAL ASSAYING
387
The variations may be caused by several factors, i.e.: (1) the age
of the plant when it is collected; (2) the season of the year when
the drug is harvested; (3) the soil and climate in which the drug is
grown; (4) the conditions under which the drug is collected,
dried, and stored. The quantity of alkaloid present in galenical
preparations is alscl ,subject to variation due to a number of
factors, some of'--which are: (a) the quality of drug employed;
(b) the menstruum used in the extraction of the alkaloid; (c)
the ltmount of decomposition of the alkaloid during the process
of extraction and during the period of storage.
Many alkaloidal preparations deteriorate comparatively
rapidly, the rate of deterioration being markedly affected by the
nature of the alkaloid, the pH value of the preparation, heat, and
light. Frequent restandardization of the alkaloidal drugs and
their preparations is therefore essential.
In view of the fact that the alkaloids may comprise only a fraction of 1 per cent of the substance assayed and that this small
amount must be separated from numerous other constituents
present in the crude drug or preparation, such as resins, volatile
and fatty oils, coloring matter, glycosides, fatty acids, gums, and
proteins, it is evident tnll1t the exact technique involved in any
given method must be carefully adhered to in order to estimate
the variations in alkaloidal content. It is this special technique
that characterizes the chemicai assay of alkaloidal drugs rather
than the gravimetric or volumetric nature of the procedure
employed.
The principles employed in the quantitative determination of
the alkaloids by chemical methods are based upon certain
characteristic properties of these substances. The following
general properties are possessed by most of the members of this
class of compounds: (1) Alkaloids are usually sparingly soluble
in water but readily soluble in certain organic solvents which are
immiscible with water, such as chloroform, ether, amyl alcohol,
benzene, petroleum benzin, or mixtures of these solvents. (2)
Alkaloids combine directly with acids to form salts which are
usually soluble in water but insoluble in certain organic solvents
such as chloroform and ether. (3) Alkaloids are liberated and
usually precipitated from aqueous solutions of their salts by
alkalies. (4) Alkaloids form highly insoluble precipitates with a
388
ALKALOIDAL ASSAYING
389
390
ALKALOIDAL ASSAYING
391
-x
100
C acid
= 2~~ and
Ce>her
= 11~0 x. If the
392
0.1~15~ Xl
= 9 and
100
Xl
WALES,
393
ALKALOIDAL ASSAYING
TABLE LX.-INDICATORS FOR ALKALOIDAL TITRATIONS
Salt of
Average
pH
pH range
for
indicator
Aconitine ................. .
Arecoline ................. .
Atropine .... '" .......... .
Brucine .................. .
Cephaeline. . . . . . . . . . . .. '"
Cinchonine ............... .
Cinchonidine .............. .
COcaine .................. .
Codeine .................. .
Cotarnine ................ .
Diacetyl morphine. .. . .... .
Emetine .................. .
Ethyl hydrocupreine ....... .
Ethyl morphine ........... .
Homa,tropine .............. .
5.04
4.81
5.56
4.85
4.81
6.02
5.90
5.20
4.86
5.97
4.89
4.90
6.33
4.99
5.'14
4.2 to 5.8
3:8 to 5.8
3.8 to'7.2
3.9 to 6.0
4.2 to 5.4
5.5 to 6.5
5.4 to 6.4
4.0 to 6.5
3.6 to 6.3
4.9 to 7.0
4.2 to 5.7
4.2 to 5.6
5.6 to 7.0
4.2 to 5.8
3.9 to 7.6
Hydrastine ............... .
4.45
3.8 to 5.0
4.83
5.83
3.6 to 5.6
3.8 to 7.6
Morphine ................. .
Narcotine ................ .
Nicotijle .................. .
Papaverine ............... .
4.68
4.43
5.26
4.23
4.0 to
3.9 to
4.4 to
3.8 to
Physostigmine ............ .
Pilocarpine ............... .
Quinine .................. .
Quinidine ................. .
Strychnine ................ .
Thebaine ................. .
Yohimbine ................ '1
4.85
4.31
6.12
6.10
4.81
5.08
4.72
3.8 to 6.0
3.6 to 5.0
5.5 to 6.5
5.5 to 6.5
3.8 to 6.0
4.0 to 6.2
4.0to5.3
5.2
4.9
6.1
4.6
Indicator
Methyl red
Methyl red
Methylred
Methyl red
Methyl red
Bromcresol purple
Bromcresol purple
Methyl red
Methyl red
Bromcresol purple
Methyl red
Methyl red
Bromcresol purple
Methyl red
Methyl red, propyl red,
bromcresol purple
No end poin t wi th
methyl red or bromphenol blue
Bromphenol blue
Methyl red, propyl red,
bromcresol purple
Methyl red
Bromphenol blue
Methyl red
Indistinct, cannot be
titrated
Methyl red
Bromphenol blue
Bromcresol purple
Bromcresol purple
Methyl red
Methyl red
Methylred
Alkaloidal Test Solutions.-A number of reagents form insoluble compoubds with many of the alkaloids precipitating the
latter from aqUeous solution. In many cases, the presence of a
mere trace of alkaloid can be detected by adding a suitable
394
ALKAWIDAL ASSAYING
395
396
ALKALOIDAL ASSAYING
397
398
1-
I
oil
~
1
!
Le.
ALKALOIDAL ASSAYING
399
tion and of 10 cc. portions of 0.5 N or 2 per cent acid for succeeding extractions will be found to be practical and convenient. The
shaking of the immiscible solvents should not be violent, but it
should be sufficient to mix them thoroughly without emulsification. Repeated successive extractions with small portions of the
acid must be continued until the alkaloid is completely removed
from the ethereal or chloroformic liquid as shown by tests with
the designated reagents. Each portion of the acid solution
should be carefully separated from the organic solvent and run
directly into another separatoryfunnel. In all assays, the extraction should be continued until 0.5 cc. of the last acid washing
shows no turbidity on the addition of a drop of mercuric
potassium iodide T.S., or, in the case of caffeine and colchicine,
on the addition of a drop of iodine T.S. If traces of organic
solvent are drawn off with the acid solution, they may be
removed by washing the combined acid extractives with 2 to 3
cc. of ether or chloroform which is separated and washed in turn
with about 5 cc. of distilled water, the aqueous washings being
separated and added to the acid solution.
If sulfuric acid is used, the acid converts the free alkaloids dissolved in the organic solvent into their sulfates which pass into
solution in the aqueous acid layer of the immiscible solvents when
the mixture is shaken, leaving chlorophyll, resins, fixed and
volatile oils, and other impuritIes dissolved in the organic solvent.
The rate at which the alkaloids pass from solution in the organic
solvent into the acid solution is increased greatly by shaking the
mixture, since a greater area of contact surface between the
liquids is produced. Sulfuric acid solution is employed to extract
the alkaloids, because the ammonium sulfate formed in the next
step in the procedure is not appreciably solub~e in the organic
solvent used for the final extraction of the alkaloid.
5. Extraction of the Alkaloids from Acid Solution with Organic
Solvents.-The acid solution of the alkaloids contained in a
separatory funnel is made alkaline, in most cases with ammonia
T.S., and then shaken with several successive portions of organic
solvent, such as ether, chloroform or ether-chloroform mixture.
The volume of organic solvent used in each extraction should be
at least one-half that of the aque<;ms solution. The extraction
with portions of organic solvent must be repeated as long as any
400
alkaloid is extracted by the solvent. To determine the completion of extraction, evaporate 1 cc. of the last washing and dissolve
the residue in a few drops of diluted hydrochloric acid; the resulting solution should show no turbidity on the addition of a drop
of mercuric potassium iodide T.S., or, in the case of caffeine and
colchicine, on the addition of a drop of iodine T.S. The number
of extractions required depends largely on the character of the
alkaloid. With most alkaloids it is advisable to extract three or
four times before testing. Physostigmine and pilocarpine
require about twice as many extractions as other alkaloids.
The ammonia reacts with the alkaloidal sulfates contained in
the aqueous solution to form the free alkaloids and ammonium
sulfate. If considerable quantities of alkaloid are contained in
the acid solution, the alkaloids may be precipitated when the
alkali is added. Consequently, the first portion of organic
solvent is added prior to the addition of the ammonia water to
dissolve any alkaloidal precipitate formed. If this procedure is
not followed, the precipitate frequently agglomerates into large
particles which dissolve slowly when the organic solvent is
added.
6. Evaporation of Organic Solvents.-The evaporation of the
final alkaloidal solution in organic solvents may be perfllrmed by
distillation with recovery of the solvent, by evaporation on a
steam bath or sand bath, or in a current of warm air. When the
evaporation is conducted on a steam bath, precautions must be
observed to prevent the ignition of the vaporized solvent. The
operation may be performed by heating a prepared water bath
until the water boils, turning out the flame, and placing the
alkaloidal solution contained in a suitable container on the bath.
If a sand bath is employed, it should preferably be of the steamheated type and the temperature of the bath should be about
60C.
Chloroform tends to form unstable compounds with many
alkaloids; consequently, when chloroformic solutions of the
alkaloids are evaporated, the residue may retain traces of
chloroform rather tenaciously. These traces of chloroform are
best removed by treating the alkaloidal residue with 2 to 3 cc.
of ether or alcohol and evaporating the solution to dryness again.
This is a wise pr~caution to employ in the evaporation of all
ALKALOIDAL ASSAYING
401
solutions of alkaloids in organic solvents when the final determination is made by volumetric methods in order to remove small
traces of ammonia which may be occluded in the alkaloidal residue, particularly if the latter is gummy in nature.
Those alkaloids which have the structure of esters such as
atropine, hyoscyamine, and cocaine and some others are decomposed more or. less by heat and by prolonged contact with water
and strong acids and alkalies. Consequently, their solutions
should be evaporated at a low temperature, usually at about
60C.; and, if it is necessary to allow the alkaloid in solution to
stand from one laboratory period to the next before the assay can
be completed, it should be shaken out of acid or alkali solutions
into an organic solvent and kept in a tightly stoppered flask.
7. Gravimetric Determinations of Alkaloids.-If the alkaloid is to
be estimated gravimetrically, the solvent is evaporated in the
usual manner from a previously weighed evaporating dish,
wide-mouth flask, or beaker, arid the residue is dried to constant
weight in an electric or hot-air oven and weighed. The same
procedure should be followed in drying the flask or beaker used
as is employed in drying the container with its residue. When
the residue is to be weighed, if the final solvent has been chloroform, the last traces of that solvent should be removed by
the addition of a little neutral ether or alcohol, followed by
evaporation. Care must be taken to avoid loss by decrepitation,
especially when evaporating chloroformic solutions of nux
vomica or cinchona alkaloids. Decrepitation may usually be
prevented by the addition of a little alcohol after the solution
has been reduced to a volume of 1 or 2 cc., evaporating at a low
temperature, and rotating the container during the process.
8. Volumetric Determinations of Alkaloids.-If tlie alkaloid is
directed to be assayed volumetrically, the residue should be
softened by the addition of about 1 cc. of neutral alcohol or ether,
the required amount of standard acid added, and the mixture
gently warmed to insure the complt'~te solution of the alkaloid.
If preferred, the alkaloidal residue may be dissolved in chloroform, the standard acid added, and the chloroform removed by
evaporation. Before titrating add a sufficient quantity of distilled water to make the volume of the mixture measure about
25 cc. The amount of acid in excess of that which combines
402
CHAPTER XXV
OFFICIAL TYPE METHODS
The official alkaloidal drugs and the galenical preparations
containing alkaloids are assayed by two type methods and
by special methods. The type methods are (1) the aliquot part
method for drugs and galenical preparations and (2) the total
extraction method for drugs and galenical preparations. The
procedures in the following assays are taken almost verbatim from
the U.S.P. and N.F., slight changes being introduced where
necessary to include more specific details.
Gravimetric Assays by the Aliquot-part Method
Exercise 114
The alkaloids found in the rhizomes and roots (If hydrastis consist chiefly of hydrastine and berberine in varying proportion.
The latter is almost inactive, while the hydrastine is very active
physiologically. Consequently, a determination of the total
alkaloids of hydrastis would not ~be a correct measure of the
therapeutic activity of the drug. Ether is used, therefore, as the
organic solvent in the extraction of the alkaloids, because hydrastine is readily soluble and berberine is practically insoluble in this
solvent. The aliquot portion of 50 cc. of the ethereal solution is
equivalent to 59100 X weight in grams of the sample of hydrastis.
403
404
2. "Extract the alkaloids completely from the ethereal solution by shaking with successive small portions of dilute sulfuric acid (about 1 per cent).
Combine the acid solutions in a separator, add about an equal volume of
ether, then add a slight excess of ammonia water, and immediately shake to
extract the alkaloids." (See General Procedure 4, page 398.)
405
16%00
X the weight of
406
4. "Make the acid solution strongly alkaline with ammonia T.S. and
completely extract the alkaloids with chloroform. Evaporate or distil the
chloroform in a tared beaker or flask and dry the alkaloidal residue to constant weight at 100C. The weight obtained, multiplied by 25, represents
the per cent of the alkaloids of cinchona in the drug." (See General Procedures 5, 6, and 7, page 399.)
407
408
409
complete solution and to remove all of the ether. Cool, and titrate the
excess of acid with tenth-normal sodium hydroxide, using methyl red T.S.
as the indicator. Each cubic centimeter of tenth-normal sulfuric acid is
equivalent to 0.0240 Gm. of the ether-soluble alkaloids of Ipecac." (See
General Procedures 5, 6, !ltnd 7, page 399.)
The ammonia sets the emetine and cephaeline free, and the
liberated alkaloids dissolve in the ether.
The residue consists almost entirely of emetine and cephaeline
which dissolve in the standard acid solution, forming emetine
and cephaeline sulfates, as illustrated by the following reaction
for emetine:
2C16H2202N
+ H2S0C~(C15H2202N)2.H2S04
Object.-Assay of Areca.
Materials Required.-15 Gm. of a'teca.
250 cc. of ether.
15 of a saturated solution of sodium bicarbonate (about 1 in 10).
About 3 Gm. of sodium bicarbonate.
Procedure.-l. "Place 15 Gm. of Areca, in moderately fine powde!' and
accurately weighed, into a suitable flask, add 150 cc. of ether, allow to stand
about five minutes, then add 15 ce. of a saturated solution of sodium bicar-
410
bonate. Agitate the mixture in a mechanical shaker for one hour, or intermittently during two hours, set it aside overnight, and again agitate in a
mechanical shaker for one hour. Separate 100 cc. of the clear ethereal
liquid." (See General Procedure 3A, page 395.)
The arecoline and guvacoline which are soluble in \ all proportions in water and in ether form salts of the acid which are soluble
in water but very slightly soluble in ether.
3. "Extract the alkaloid completely from the alkaline liquid with successive portions of ether. Filter the ethereal solutions successively into 10 cc.
of tenth-normal sulfuric acid, rotating after each addition. Evaporate the
ether from this mixture, and determine the alkaloid by titration of the
excess acid with fiftieth-normal sodium hydroxide, using cochineal T.S. or
methyl red T.S. as the indicator.
"Each cubic centimet!-lr of tenth-normal sulfuric acid represents 0.0155
Gm. of arecoline, CSH1302N." (See General Procedures 5, 6, and 7,
page 399.)
2CsH 130 2N
+ H2S04-(CsH1302N)2.H2S04
411
Substance
Amount
used,
Gm.
or cc.
Assayed
for
Official
requirement,
per cent
U.S.P.
Cinchona ...............
Cinchona, compound tincture of ...............
Ipecac .................
Total alkaloids
(n.l.t.) 5
50
10
0.4 to O.5W jV
(n.Lt.) 2
10
Total alkaloids
Ether-soluble
alkaloids
Ether-soluble
alkaloids
N.F.
Areca ..................
Hy\lrastis ...............
15
10
Arecoline
Ether-soluble
alkaloids
Ether-soluble
alkaloids
Ether-soluble
alkaloids
Ether-soluble
alkaloids
Ether-soluble
alkaloids
(n.l.t.) 0.2
(n.l.t.) 2.5
2*
Hydrastis, fluidextract of
5*
25*
50*
1. 8 to 2. 2W jV
to 11
2.25 to 2. 75W jV
0.45 to 0.55WjV
0.18 to 0.22W jV
412
drug with a mixture of 8 cc. of stronger ammonia T.S., 10 cc. of alcohol and
20 cc. of ether, and mix thoroughly. Macerate the mixture over night, then
extract it for not less than three hours on a water bath, using 'ether as the
solvent. The following alternative process may be used: Moisten 25 Gm.
of Hyoscyamus, in fine powder, with a mixture of 8 cc. of stronger ammonia
T.S., 20 cc. of ether and 10 cc. of chloroform, in a small Ilercolator, previously
prepared by packing the outlet with a pledget of purified cotton. Macerate
the mixture over night, paek it in the percolator and extract by slowly percolating with a mixture of 3 parts of ether and 1 part of chloroform, by
volume. Continue the percolation until the 3 or 4 cc. of percolate last
passed, when evaporated to dryness and the residue dissolved in dilute
sulfuric acid, fails to become turbid when treated with mercuric potassium
iodide T.S." (See General Procedure 3B and C, page 397.)
The large volume of liquid obtained, especially by cold percolation, is concentrated to a small volume to secure a convenient
amount. It should not be evaporated to dryness because the
chlorophyll and other non-alkaloidal residue make it difficult
to completely dissolve the alkaloids in the acid. The alkaloids,
hyoscamine and atropine, being esters undergo hydrolysis readily
in aqueous acid and alkaline solution especially when heated.
Consequently, the evaporation of the organic solvent should be
conducted at a low temperature, preferably not exceeding 40C.,
after the addition of the acid. The evaporation may be carried
out advantageously in a vacuum desiccator under reduced pressure. Upon filtration, the non-alkaloidal residue consisting
mostly of chloropyll is retained on the filter. This residue is
dissolved in chloroform, treated with acid, and evaporated to
413
The alkaloids are set free by the ammonia water and dissolve
in the chloroform.
4. "Evaporate or distil the chloroform from the combined extractions
until reduced to a small volume, then evaporate to dryness on a water bath,
and keep at this temperature for fifteen minutes. Dissolve the residue in
chloroform, evaporate to dryness on a water bath, and continue the heating
for fifteen minutes. Repeat this treatment for the third time."
2C 17H 23 0 3N
289.3
+ H2S04~(C17H2303N2).H2S04
98
414
is equivalent to 2
~ ~ ~9i~000 =
415
hyoscya~us.
416
Substance
U.S.P.
Belladonna leaf ................... .
Belladonna ointment .............. .
Belladonna, pilular extract of ...... .
Belladonna plaster ................ .
Belladonna, powdered extract of ... .
Belladonna root ................... .
Belladonna root, fluidextract of .... .
Belladonna, tincture of ............ .
Hyoscyamus ...................... .
Hyoscyamus, pilular extract of ..... .
Hyoscyamus, powdered extract of .. .
Hyoscyamus, tincture of ........... .
Stramonium ....... '............... .
Stramonium, pilular extract of ..... .
Stramonium, powdered extract of ...'
Stramonium, tincture of ........... .
N.F.
Belladonna leaf, fluidextract of ..... .
Hyoscyamus, fluidextract of . ...... .
Stramonium, fluidextract of ........ .
(n.l.t.)
Amount
used,
Gm.or
cc.
Official
requirement,
per cent
10
25
3
10
2
10
10
100
25
5
5
250
10
3
2
100
(n.l.t.) l3
O. 118 0 O. 132
1.18 to 1.32
0.25 to 0.30
1.18 to 1.32
(n.l. t.) 0.45
0.405 to 0.495WjV
0.027 to 0.033WjV
(n.l.t.) 0.040
0.135 to 0.175
0.135 to 0.175
0.0034 to 0.0046WjV
(n.l.t.) 0.30
1.10 to 1.30
1.10 to 1.30
0.027 to 0.033WjV
10
25
10
0.27 toO.33W/V
0.035 to 0.045WjV
0.25 to 0.35WjV
417
CHAPTER XXVI
ALKALOIDAL ASSAYS BY SPECIAL METHODS
Object.-Assay of Opium.
Materials Required.-6 Gm. of opium.
3 Gm. of freshly slaked lime.
1 G~. of ammonium chloride.
100 ce. of ether.
25 cc. of water saturated with morphine.
Procedure.-l. "Triturate in a mortar 6 Gm. of the Opium to be assayed
which, if fresh, should be in very small pieces, and if dry, in fine powder, with
about 40 cc. of distilled water for fifteen minutes. Transfer the mixture
completely to a flask with the aid of 30 cc. of warm distilled water, stopper
the flask, and shake it every ten minutes, or continuously in a mechanical
agitator, during one hour. Pour the contents as evenly as possible upon a
wetted filter of from 10 to 11 cm. in diameter or, preferably, upon a sintered
glass funnel attached to a suction flask. When the liquid has drained off,
wash the residue with abollt 20 cc. of distilled water, carefully dropped upon
the edges of the filter and its contents. Transfer the moist residue to a
mortar, rub it to a smooth paste, then rinse it into the original flask with
40 cc. of distilled water, agitate it thoroughly during ten minutes, and return
the entire mixture to the filter. When the liquid has drained off, wash the
residue with small portions of distilled water until the washings are nearly
colorless. "
419
420
and, after shaking the mixture, add 1 Gm. of ammonium chloride. Stopper
the flask, shake it frequently during ten minutes and set it aside in a cool
place over night. Remove the stopper and brush any adhering crystals back
into the flask."
421
422
Amount
Equivalent
used,
of 1 cc. of
Gm. or
0.1 N H 2SO 4
cc.
Substance
U.S.P.
Opium ............. , ....
Opium, granulated ...... "
Opium, powdered .........
Opium, tincture of ........
Opium, tincture of, camphorated ..............
6
6
6
60
0.02852
0.02852
0.02852
0.02852
100
0.00570*
9.5
10
to 10.5
10
to 10.5
0.95 to 1.05W/V
0.035 to 0.0045
N.F.
Opium, extract ...... , ....
* Equivalent of 1
CC.
0.02852
19.~
.....
to 20.5
of 0.02 N H 2SO
Exercise 123
423
which the alkaloid must be separated. The free alkaloid, colchicine, is miscible in all proportions with water, and it is extracted
from the drug when the latter is digested with water. The
digestion temperature should not exceed 70C., because the
starch content of the drug, especially of the corm, is gelatinized
at higher temperatlJres, and because colchicine is less soluble in
hot than in cold water. The lead subacetate is added to prevent
solution of the tannin, gums, resin, and coloring matter with
which it forms water-insoluble compounds and to liberate the
colchicine from acids with which it may be combined in the crude
drug. The mixture is cooled, and distilled water is added to
restore the original weight of the sample, water, and lead subacetate mixture, so that an aliquot portion, corresponding to a
definite weight of the sample taken, may be used. Two hundred
cubic centimeters of the liquid representing the alkaloids contained in two-thirds of the weight of the sample are filtered off.
2. "Add 2 Gm. of sodium phosphate to the clear filtrate, or sufficient to
precipitate the lead completely, shake the mixture frequently during half an
hour, ffiter, collect 100 cc. of ffitrate, representing 5 Gm. of Colchicum Seed."
424
4. "To this weighed residue in the flask, add 5 cc. of tenth-normal sulfuric
acid, 5 cc. of distilled water, and a few drops of chloroform, and heat the
mixture at 70C. for ten minutes. Filter the liquid through a pledget of
purified cotton, wash the flask and cotton with distilled water, reject the
filtrate and washings, and remove as much of the water from the cotton as
possible. Dissolve the residue, if any, which may remain on the cotton by
washing it first with a little alcohol and then with ether; collect the alcoholether washings in the flask, evaporate, and dry the residue to constant
weight at 100C. Deduct this weight from the weight of residue previously
obtained. The difference is the weight of colchicine obtained from 5 Gm.
of CoI<:hicum Seed."
425
Substance
Amount
used
U.S.P.
Colchicum seed ............ 15 Gm.
Colchicum seed, tincture of 150 cc.
Colchicine, official
requirement,
per cent
5 Gm.
50 cc.
0.45
0.036 to 0.044W IV
N.F.
Colchicum corm ...........
Colchicum corm, fluidextract of. ................
Colchicum corm, strong
tincture of ..............
Colchicum seed, fluidextract
of .....................
15 Gm.
5Gm.
0.35
15 cc.
5 cc.
0.31 to 0.39WIV
45 cc.
15 cc.
0.125 to 0.155WIV
15 cc.
5 cc.
0.4
toO.5WIV
Exercise 124
426
hour. Now allow the mixture to stand for twelve hours or over night in a
cool place, At the expiration of this period, shake the container gep.tly for
fifteen minutes, and then allow the liquids to separate."
427
428
dissipated. Cool to room temperature and titrate the excess of acid with
fiftieth-normal sodium hydroxide, using 1 drop of methyl red T:S. as the
indicator. Each cubic centimeter of tenth-normal sulfuric acid is equivalent
to 0.03342 Gm. of strychnine."
+ H2S04---+(C21H2202N2)2.H2S04
2C21H2202N2
334.19
Nux
VOMICA AND
Amount
used,
Gm. or
cc.
Substance
U.S.P.
Nux
Nux
Nux
N.F.
Nux
Nux
VOMICA PREPARATIONS
Official'requirement,
per cent
15
Strychnine = (n.Lt.) 1.15
1.5 Strychnine = 7 to 7.75
100
Strychnine = 0.108 to 0.120
10
429
Object.-Assay of Guarana.
Materials Required.~ Gm. of guarana in No. 60 powder.
250 cc. of chloroform.
Procedure.-l. "Place 6 Gm. of Guarana, in fine powder and accurately
weighed, into a suitable container, add 120 cc. of chloroform, allow the
mixture to stand about five minutes, and then add 6 cc. of ammonia water
and 6 cc. of distilled water. Shake t.he mixture continuously for one hour
or intermittently dUring two hours, and allow it to stand overnight.
Again shake intermittently during one half hour and separate 100 cc. of
the clear chloroformic solution."
430
small portions of distilled water until no test for alkaloid is obtained with
iodine T.S. in a portion (1 cc.) of the filtrate after a:cidulating strongly with
diluted sulfuric acid."
1. Why is not the caffeine extracted from the chloroformic solution with
dilute acid in the usual manner?
2. Could mercuric potassium iodide solution be used to test for the complete extraction ,of the caffeine from the acid solution?
431
Amount
used,
Official requirement,
Gm. or
per cent caffeine
cc.
Substance
N.F.
Guarana .................
Guarana, fluidextract of ...
Kola ...................
Kola, fluidextract of .......
.
.
.
.
6
5
12
10
4.0
3.6 to 4.4 W IV
1.0
0.85 to 1.15W IV
432
+ NaOH----+NaCI + H
C5H7N(CH3)30(C6H5CO)
The liberated alkaloid is dissolved in the alcohol.
Each cubic
0.02836
433
weighed, in 10 cc. of warm distilled water, and titrate the solution with
normal hydrochloric acid, using phenolphthalein T.S. as the indicator: not
more than 5.5 cc. of normal hydrochloric acid is required to neutralize 2 Gm.
of the dried Theobromine with Sodium Salicylate."
434
435
Exercise 130
The extracted ephedrine is dissolved by the alcohol and converted quantitatively to ephedrine hydrochloride by the acid:
C 1oH 150N
165.13
+ HCl~ClOH150N.HCl
201.60
436
Substance
U.S.P.
Caffeine, citra ted ............... .
Caffeine with Bodium benzoate .. . .
Codeine phosphate ............. .
Ephedrine ..................... .
Ephedrine hydrochloride ........ .
Ephedrine Bulfate . ... " ......... .
Ethylhydrocupreine hydrochloride
Eucaine hydrochloride .......... .
Phenacaine hydrochloride ....... .
Quinine and urea hydrochloride . . .
Theobromine with sodium salicylate ......................... .
Theophylline with ethylene diamine ........................ .
Amount
used,
Gm. or
cc.
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
Anhydrous caffeine = 48 to 52
Anhydrous caffeine = 47 to 50
Anhydrous codeine = (n.l.t.) 70
Ephedrine = 98 to 100
Anhydrous ephedrine = 80 to 82.5
Anhydrous ephedrine - '(:5.5 to 77.3
Ethylhydrocupreine = (n.l. t.) 90
Eucaine hydrochloride = (n.l.t.) 99
Phenacaine = 87.5 to 90.5
Anhydrous quinine = 58 to 65
Anhydrous, theophylline = 70 to 80
Anhydrous theophylline = 55 to 65
1
1
0.2
10
0.2
0.5
Anhydrous caffeive
= 45 to 52b
0.5
0.5
0.5
0.13
0.06
0.13
0.4
0.13
CHAPTER XXVII
OTHER OFFICIAL ASSAYS INVOLVING THE USE OF
IMMISCIBLE SOLVENTS
Use is made of the immiscible solvent principle of extraction
and purification in the proximate determination of the amount
of active constituent contained in a number of non-alkaloidal
drugs such as jalap, cantharides, and oleoresin of aspidium and
in the assay of certain synthetic medicinal products, e.g., soluble
barbital.
Exercise 131
Object.-Assay of Cantharides.
Materials Required.-15 Gm. of cantharides in No. 40 powder.
75 cc. of purified petroleum benzin.
100 cc. of benzene.
50 cc. of chloroform.
25 cc. of absolute alcohol.
Procedure.-l. "Place 15 Gm. of Cantharides, in moderately coarse
powder, in a pressure bottle' of not less than 250 cc. capacity, add 150 cc. of a
mixture of benzene, two volumes, and purified petroleum benzin one volume,
and then add 2 cc. of hydrochloric acid. Stopper the bottle tightly, shake
it well, and allow it to stand about ten hours. Now gradually warm the
bottle and its eontents to about 40C. and maintain it at approximately
that temperature with frequent shaking during three hours, avoiding
evaporation. If necessary, add more solvent to replace any lost by
evaporation."
438
439
440
The filicic acid and filicin are liberated from their barium salts
and dissolved in the ether, leaving barium chloride in the aqueous
solution.
3. "Filter the combined ethereal solutions, wash the filter with ether,
evaporate, and dry the residue to constant weight at 100C. This residue
is calculated as crude filicin and its weight should be not less than 24 per
cent of the weight of Oleoresin taken for the assay."
Exercise 133
Object.-Assay of Jalap.
Materials Required.-lO Gm. of jalap in No. 60 powder_
20 cc. of 1 per cent hydrochloric acid.
90 cc. of chloroform.
120 cc. of alcohol.
Procedure.-l. Place 10 Gm. of jalap, in fine powder and accurately
weighed, with about 60 cc. of a mixture of 9 volumes of alcohol and 1 volume
of water, in a flask provided with a reflux tube or condenser, and digest the
mixture on a steam bath during Y2 hr. Transfer the warm mixture to a
small-percolator, allow it to drain, press the marc down gently, and percolate
with the warm alcohol-water mixture until 100 cc. of percolate, when cooled,
is obtained, and mix thoroughly.
441
442
NON-ALKALOIDAL
SUBSTANCES
ASSAYED
BY
Substance
U.S.P.
Aspidium ........................... .
Aspidium, oleoresin of ................ .
Cantharides. . . . . . . . . . . . . . . . .. ... . ..
Podophyllum ................. .
Soluble barbital. ............. .
Soluble phenobarbital. ..
N.F.
Acetophenetidin, tablets of. .......... .
Acetophenetidin and phenyl salicylate,
tablets of. .. .. . . . . .. . ........ .
Aminopyrine, elixir of . ......... .
Aminopyrine, tablets of. . . .. . ..
Barbi tal, elixir of. . . .. ...... .
Barbital, tablets of, more than 0.07 Gm ..
0.07 Gm. orle8s .......... .
Ipomoea .................. .
Jalap...... . . . . . . . . . . . . . . . . . .
Jalap, fluidextract of. .. . . ... ..
Jalap, tincture of ...... , ... .
Phenobarbital, elixir of ........ .
Phenobarbital, tablets of
more than 0.07 Gm .. : .......... .
0.07 Gm. or less ....
Soluble barbital, tablets of
more than 0.07 Gm ............... .
0.07 Gm. or less .................. .
Soluble phenobarbital, tablets of
more than 0.07 Gm ...
0.07 Gm. orless ...
Amount
used,
Gm. or
cc.
0.5
0.3
5
I"
10
0.3"
0.3
10
10
2
10
25
125
3
15
10
0.3
0.3
0.3
0.3 a
0.3 a
0.3
443
and wash the cotton with small portions of the solvent. Evaporate the
combined filtrate and washings on a water bath with the aid of a current of
air, and dry the residue of phenobarbital to constant weight at a temperature
not exceeding 100C."
The Hel liberates the phenobarbital from the soluble" phenobarbital and the-liberated phenobarbital is dissolved and extracted
upon shaking with successive portions of the mixed organic
solvents_
Questions and Problems
1. Calculate the amount of phenobarbital in each of the tablets.
2. Docs thc amount of phenobarbital found fall within the tolerance
limits established for these tablets in the National Formulary?
3. Consult the U.S. Pharmacopoeia for the formulae of phenobarbital
and soluble phenobarbital and write equations for the reactions that occur
in the assay using graphic for~ulae.
CHAPTER XXVIII
ASSAY OF ENZYME-CONTAINING SUBSTANCES
No methods are known whereby the quantity of enzymes in a
substance can be accurately determined. ,Consequently, the
assay of enzyme-containing substances is based on observations
of their power to produce changes in other substances. In
other words, the activity of the enzymes is measured. Thus,
pepsin is evaluated on the basis of the quantity of egg albumen
which it will digest, and extract of malt is assayed for its power to
convert starch into soluble carbohydrates under definite conditions. Any condition which tends to increase or decrease the
activity of the en'zymes manifests itself in the assay results as
an increase or decrease in the quantity of enzyme;; present.
Numerous factors tend to influence the activity of enzymes.
Some of the more important of these factors are as foqows:
L Practically all enzymes are destroyed when they are heated
to 100C. Many 'of them are gradually inactivated at comparatively low temperatures (35 to 40C.), and many of them
undergo a slow loss of activity at room temperature and even at
OC.
2. Enzymes have an optimum temperature of action; that is,
for each enzyme there is a definite range of temperature at
which it exhibits its maximum activity under definite conditions.
The optimum temperature for most enzymes lies between 30 and
45C.
3. The activity of the enzymes is affected by the media in
which they react; e.g., pepsin is most active in acid media, and
pancreatin is most active in alkaline media.
4. The enzymes are inactivated by many chemical agents,
such as alcohol, salts of the heavy metals, tannin, and phosphotungstic acid, which precipitate the enzymes from solution.
Because the activity of enzymes is influenced by so many
factors, it is necessary to adhere strictly to the procedures out444
445
Object.-Assay of
P~psin.
When 35 cc. of normal Hel is diluted to 420 cc., the concentration of acid in the solution is reduced to approximately 0.3 per
cent. This is about the normal acidity of the stomach. Investigation has shown that pepsin is most active as an albumen digestive in media containing this concentration of acid. Other
strongly dissociated acids which supply the same hydrogen ion
concentration as 0.3 per cent Hel might be used, since the digestive activity of the pepsin is directly related to the hydrogen ion
concentration of the reaction mixture.
2. "Immerse one or more hen's eggs in boiling water during fifteen
minutes. Cool them rapidly to room temperature by immersion in cold
water, remove the shell and pellicle and all of the yolk and at once rub the
albumen through a clean, dry, No. 40 sieve, rejecting the first portion that
passes through the sieve. Place 10 Gm. of the succeeding well-mixed portion in each of three wide-mouth bottles of about 100-cc. capacity."
446
dust particles and traces of metallic compounds from the materials of the sieve.
3. "Immediately add 35 cc. of the dilute acid at one time or in portions
and, by suitable means, disintegrate thoroughly the particles of albumen.
Place the bottles in a water bath at 52C. After the contents of the bottles
have reached that temperature, add exactly 5 cc. of the acidulated solution
of Pepsin to one bottle, 4.30 oc. of the same solution and 0.70 co. of the dilute
acid to another bottle, and exactly 5 cc. of the acidulated solution of Reference Pepsin to the third bottle. At onoe stopper the bottles s'ecurely, invert
them three times, and maintain them at a temperature of 52C. for two and
one-half hours, agitating the contents equally every ten minutes by inverting
the bottles once."
447
448
The percentage of moisture remaining in the stch is determined so that a sample equivalent to 3.75 Gm. of dry starch
can be used for digestion. Thus, if the sample dried at 500.
is found to contain 10 per cent of moisture, each gram of the
sample is 'equivalent to 0.9 Gm. of dry starch. Then 3.75/0.9 =
4.1666 Gm. starch equivalent to 3.75 Gm. of dry starch.
The starch is mixed with cold water to obtain a paste so that it
will not form lumpy masses when the hot water is added. When
this paste is added to warm water and the resulting mixture is
boiled, the starch grains burst, liberating their contents which
dissolve in the hot water to form a more or less mucilaginous
mass. Until the starch grains are broken down in this way,
they remain insoluble and are not acted upon by pancreatin.
2. "Add enough distilled water to make the mixture weigh 100 Gm.,
cool the paste to 40C., and place the beaker on a water bath maintained
at 40C. Suspend 0.15 Gm. of Pancreatin in 5 cc. of distilled water and add
the suspension to the starch paste, mixing it well by pouring the mixture
from beaker to beaker for thirty seconds, noting the time when the Pancreatin suspension was added to the starch. Maintain the mixture at a
temperature of 40C. for exactly five minutes."
449
450
Immediately immerse the test tube in a water bath at 400., and 'keep it
at this temperature for one hour. Then remove from the bath, and add 3
drops of the acetic acid mixture. No precipitate is produced."
~O~ =
~.~ =
0.0004 X 25 = 0.0100.
The mixture is maintained at 40C., the optimum temperature
for trypsin, for 1 hr. to allow the proteolytic action to proceed.
The casein is digested by the pancreatic enzymes with the
formation of soluble proteoses and possibly small amounts of
amino acids. When the alcoholic acetic acid solution is added,
the alkali is neutralized and any undigested casein is precipitated, since casein is insoluble in alcohol and in acetic acid.
The proteoses and other products of casein digestion, being
soluble in alcohol and acetic acid, are not precipitated. Consequently, if a precipitate is formed, it indicates that the proteolytic activity of the pancreatin is below stanQ.ard; that is,
that 1 part of the pancreatin is not capable of digesting 25 parts
of casein.
Questions and Problems
1. Why is the protein digestive capacity of pancreatin determined in an
alkaline medium?
2. Which of the enzymes of pancreatin take part in protein digestion?
3. Define the term optimum temperature as applied to enzymes.
4. How might the relative proteolytic power of a sample of pancreatin
stronger or weaker than the official standard be determined?
Exercise 138
Object.-Assay of Rennin.
Materials Required.--o.l Gm. of rennin.
0.1 Gm. N.F. reference rennin (a carefully preserved, stable, powdered
rennin that has been repeatedly tested for a number of years so that its
stability and its standard are definitely established. It coagulates approximately but not less than 25,000 times its weight of fresh cow's milk).
100 cc. of cow's milk.
451
452
Substrate
Substance
Official requirement
\
U.S.P.
Malt, extract of. . . . . . . .. Potato starch
Pancreatin ............ , Potato starch
Casein
N.F.
Pepsin, compound elixir Egg albumen
of
Pepsin, elixir of. . . . . . . .. Egg albumen
Pepsin, elixir of and ren- Egg albumen
run
453
APPENDIX
LOGARITHMS OF NUMBERS
Proportional parts
Natural
numbers
9
11213141516171819
12
13
14
10
0000 0043 0086 0128 0170 0212 0253 0294 0334 0374
0414 0453 0492 0531 0569 0607 0645 0682 0719 0755
0792 0828 0864 0899 0934 0969 1004 1038 1072 1106
1139 1173 1206 1239 1271 1303 1335 1367 1399 1430
1461 1492 1523 1553 1584 1614 1644 167a 1703 1732
4
4
3
3
3
8 12 17 21 25 29 3337
811 15 19 23 26 30 34
7 10 14 17 21 24 2831
6 10 13 16 19 23 2629
6 912 15 1821 24 27
15
16
17
18
19
1761 1790 1818 1847 1875 1903 1931 1959 1987 2014
2041 2068 2095 2122 2148 2175 2201 2227 2253 2279
2304 2330 2355 2380 2405 2430 2455 2480 2504 2529
2553 2577 2601 2625 2648 2672 2695 2718 2742 2765
2788 2810 2833 2856 2878 2900 2923 2940 2967 2989
3
3
2
2
2
6
5
5
5
4
20
21
22
3010 3032 3054 3075 3096 3118 3139 3160 3181 3201
3222 3243 3263 3284 3304 3324 3345 3365 3385 3404
3424 3444 3464 3483 3502 3522 3541 3560 3579 3598
3617 3636 3655 3674 3692 3711 3729 3747 3766 3784
3802 3820 3838 3856 3874 3892 3909 3927 3945 3962
2
2
2
2
2
4
4
4
4
4
25
26
27
28
3979 3997 4014 4031 4048 4065 4082 4099 4116 4133
4150 4166 4183 4200 4216 4232 4249 4265 4281 4298
4314 4330 4346 4362 4378 4393 4409 4425 4440 4456
4472 4487 4502 4518 4533 4548 4564 4579 4594 4609
4624 4639 4654 4669 4683 4698 4713 4728 4742 4757
2
2
2
2
1
3
3
3
3
3
5
5
5
4
80
4771 4786 4800 4814 4829 4843 4857 4871 4886 4900
4914 4928 4942 4955 4969 4983 4997 5011 5024 5038
5051 5065 5079 5092 5105 5119 5132 5145 5159 5172
5185 5198 5211 5224 5237 5250 5263 5276 5289 5302
5315 5328 5340 5353 5366 5378 5391 5403 5416 5428
1
1
1
1
1
3
3
3
3
3
4
.4
4
4
11
23
24
29
81
82
83
84
5 7 910 1214 18
7
6
6
6
810 1113 15
8 9 1113 14
8 9 1112 14
7 9 1012 13
4 6 7 910 1113
6 7 810 1112
5 7 8 9 1112
5 6 8 9 1012
5 6 8 9 1011
1 2 4
1 2 4
1 2 3
1 2 3
1 2 3
39
40
41
42
43
44
6021 6031 6042 6053 6064 6075 6085 6096 6107 6117
6128 6138 6149 6160 6170 6180 6191 6201 6212 6222
6232 6243 6253 6263 6274 6284 6294 6304 6314 6325
6335 6345 6355 6365 6375 6385 6395 6405 6415 6425
6435 6444 6454 6464 64_74 6484 6493 6503 6513 6522
1
1
1
1
1
2
2
2
2
2
3 4 5 6
3 4 5 6
3 4 5 6
3 4 5 6
3 4 5 6
45
46
47
48
~m
1
1
1
1
1
2
2
2
2
2
3 4
3 4
3 4
3 4
5
5
5
4
3 4 4
50
6990 6998 7007 7016 7024 7033 7042 7050 7059 7067 1
70711 7084 7093 7101 7110 7118 7126 7135 7143 7152 1
7160 7168 7177 7185 71937202 7210 7218 7226 7235 1
7243 7251 7259 7267 72757284 7292 7300 7308 731611
7324 7332 7340 7348 73567364 7372 7380 7388 7396 1
2
2
2
2
2
3 3 4 Ii 6 7 8
3 3 4 5 6 7 8
35
36
87
88
49
51
52
53
54
5 6 7 9 1011
5
5
5
4
6
6
6
5
7
7
7
7
8 1011
8 910
8 910
8 910
8
7
7
7
7
910
8 9
8 9
8 9
8 9
6 7 8 9
6 7 7 8
5 6 7 8
.5 6 7 8
5 6 7 8
2 3 4 5 6 7 7
2 3 4 /; 6 6 7
2 3 4 Jj 6 6 7
* See page 13 for example. illustrating the us","of logarithmic table. in calculations.
454
Proportional parts
Natural
numbers
9
11213141516171810
55
56
57
68
59
7404 7412 7419 7427 7435 7443 7451 7459 7466 7474
7482 7490 7497 7505 7513 7520 7528 7536 7543 7551
7559 7566 7574 7582 7589 7597 7604 7612 7619 7627
7634 7642 7649 7657 7664 7672 7679 7686 7694 7701
7709 7716 7723 77a1 7738 7745 7752 7760 7767 7774
1
1
1
1
1
2
2
2
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
60
61
62
63
64
7782 7789 7796 7803 7810 7818 7825 7832 7839 7846
7853 7860 7868 7875 7882 7889 7896 7903 7910 791~
7924 7931 7938 7945 7952 7959 7966 7973 7980 798
7993 8000 8007 8014 8021 8028 8035 8041 8048 8055
8062 8069 8075 8082 8089 8096 8102 8109 8116 8122
1
1
1
1
1
1 2
1 2
1 2
1 2
1 2
3
3
3
3
3
4 4 5
4 4 5
3 4 5
3 4 5
3 4 5
6
6
6
5
5
6
6
6
6
6
65
66
67
68
69
8129 8136 8142 8149 8156 8162 8169 8176 8182 8189
8195 8202 8209 8215 8222 8228 8235 8241 8248 8254
8261 8267 8274 8280 8287 8293 8299 8306 8312 8319
8325 8331 8338 8344 8351 8357 8363 8370 8376 8382
8388 8395 8401 8407 8414 8420 8426 8432 8439 8445
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
2
3
3
3
3
3
4
4
4
4
4
5
5
5
4
4
5
5
5
6
5
6
6
6
70
72
73
74
8451 8457 8463 8470 8476 8482 8488 8494 8500 8506
8513 8519 8525 8531 8537 8543 8549 8555 8561
8573 8579 8585 8591 8597 8603 8609 8615 8621 ~m
8633 8639 8645 8651 8657 8663 8669 8675 8681 8686
8692 8698 8704 8710 8716 8722 8727 8733 8739 8745
1
1
1
1
1
1
1
1
1
2
2
2
2
1 2
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5 6
5 /)
5 I)
75
76
77
78
79
8751 8756 8762 8768 8774 8779 8785 8791 8797 8802 1
8808 8814 8820 8825 8831 8837 8842 8848 8854 8859 1
8865 8871 8876 8882 8887 8893 8899 8904 8910 8915 1
8921 8927 8932 8938 8943 8949 8954 8960 8965 8971 1
8976 8982 8987 8993 8998 9004 900~ 9015 9020 9026 ,1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
5
5
4
4
4
80
81
82
83
84
9031 9036 9042 9047 9053 9058 9063 9069 9074 9079
9085 9090 9096 9101 9106 9112 9117 9122 9128 9133
9138 9143 9149 9154 9159 9165 9170 9175 9180 9186
9191 9196 9201 9206 9212 9217 9222 9227 9232 9238
9243 9248 9253 9258 9263 9269 9274 92('9 9284 9289
1 1 212
1 1 2 2
1 1 2 2
1 1 2 2
1 1 2 2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
85
86
87
89
9~4 9299 9304 9309 9315 9320 9325 9330 9335 9340
9345 9350 9355 9360 9365 9370 9375 9380 9385 9390
9395 9400 9405 9410 9415 9420 9425 9430 9435 9440
9445 9450 9455 9460 9465 9469 9474 9479 9484 9489
9494 9499 9504 9509 91?13 9518 9523 9528 9533 9538
1
1
0
0
0
1
1
1
1
1
2
2
1
1
1
3
3
2
2
2
3
3
3
3
3
4
4
3
3
3
4
4
4
4
4
90
91
92.
93
94
9542 9547 95112 9557 9562 9566 9571 9576 9581 9586
9590 9595 9600 9605 9609 9614 9619 9624 9628 9633
9638 9643 9647 9652 9657 9661 9666 9671 9675 9680
9685 9689 9694 9699 9703 9708 9713 9717 9722 9727
9731 9736 9741 9745 97!i0 9754 9759 9763 9768 97;,?3
0
0
0
0
0
1
1
1
1
1
1 2 2
1 2 2
1 2 2
1 2 2
1 2 2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
95
96
97
98
99
0777 9782 9786 9791 9795 9800 9805 9809 9814 9818
9823 9827 9832 9836 9841 9845 981)0 9854 9859 9863
9868 9872 9877 9881 9886 9890 9894 9899 9903 9908
9912 9917 9921 9926 9930 9934 9939 9943 9948 9952
99b6 9961 9965 9969 9974 9978 9983 9987 9991 9996
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
2 2
2 2
2.2
2 2
2 2
3
3
3
3
3
3 4 4.
3 4 4
71
88
2
2
2
2
2
2
2
2
2
2
5
5
5
4
4
I)
I)
5 II
IS
5
5
.5
5
5
5
.5
5
4 5
IS
/)
4
4
4.
4.
4.
4.
4.
3 4 4.
3 4 4
3 3 4.
455
APPENDIX
ANTlLOGAlUTHMS
,Proportional pa.rts
Logarithms
1009
1033
1057
1081
1107
1012
1035
1059
1084
1109
1\2\3\415\6\7181~
a a
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2 2 2
0
0
0
1
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2 2 2
2 2 2
.09
1122 1125 1127 1130 1132 1135 1138 1140 1143 1146
1148 1151 1153 1156 1159 1161 1164 1167 1169 1172
1175 1178 1180 1183 1186 1189 1191 1194 1197 1199
1202 1205 1208 1211 1213 1216 1219 1222 1225 1227
1230 1233 1236 1239 1242 1245 124'1 1250 1253 1256
.10
.11
.12
.13
.14
1259 1262
1288 1291
1318 1321
1349 1352
1380 1384
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
.15
.16
.17
.18
.19
1413
1445
1479
1514
1549
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2 3 3
2 3 3
:I 3 3
2 3 a
3 3 3
.20
.21
.22
.23
.24
1600
1637
1675
1714
1754
1603 1607
1641 1644
1679 1683
1718 1722
1758 1762
.25
.26
.27
.28
.29
1778
1820
1862
1905
1950
1795
1837
1879
1923
1968
.00
.01
.02
.03
.04
1000 1002
1023 1026
1047 1050
1072 1074
1096 1099
.05
.06
.07
.08
1005 1007
1028 1030
1052 1054
1076 1079
1102 1104
1265 1268
1294 1297
1324 1327
1355 1358
1387 1390
1271
1300
1330
1361
1393
1014 1016
1038 1040
1062 1064
1086 1089
1112 1114
1019 1021
1042 1045
1067 1069
1091 1094
1117 1119
2 2 2
2 2 2
2 2 2
2 2 2
2 2 2
2 2 3
2 2
2
2
2
3
3
3
3
3
3
1439
1472
1507
1542
1578
1442
1476
1510
1545
1581
0
0
0
0
0
1
1
1
1
1
1611 1614
1648 1652
1687 1690
1726 1730
1766 1770
1618
1656
1694
1734
1774
0
0
0
0
0
1 1 1 2 2 3 3 3
1 1 2 2 2 3 3 3
1816
1858
1901
1945
1991
0
0
0
0
0
.30
.31
.32
.33
.34
1995 2000 2004 2009 2014 2018 2023 2028 2032 2037
2042 2046 2051 2056 2061 2065 2070 2075 2080 2084
2089 2094 2099 2104 2109 2113 2118 2123 2128 2133
2138 2143 2148 2153 2158 2163 2168 2173 2178 2183
2188 2193 2198 2203 2208 2213 2218 2223 2228 2234
0
0
0
0
1
1 1 2 2 3 3 4 4
1 1 2 2 3 3 4 4,
1 1 2 2 3 3 4 4
.35
.36
.37
.3S
.39
2286
:1339
2393
2449
2506
1
1
1
1
1
1 2 2 3 3 4 4 Ii
.40
.41
.42
.43
.44
2512 2518 2523 2529 2535 2541 2547 2553 2559 2564
2570 2576 2582 2588 2594 2600 2606 2612 2618 2624
2630 2636 2642 2649 2655 2661 2667 2673 2679 2685
2692 2698 2704 2710 2716 2723 2729 2735 2742 2748
2754 2761 2767 2773 2780 2786 2798 2799 2805 2812
1
1
1
1
1
1
1
1
1
1
3
3
3
3
3
4
4
4
4
4
4 5 6
4 II 6
.45
.46
.47
.48
.49
2818 2825 2831 2838 2844 2851 2858 2864 2871 2877
2884 2891 2897 2904 2911 291.7 2924 2981 2938 2944
2951 2958 2965 2972 2979 2985 2992 2999 3006 3013
3020 3027 3034 3041 3048 3055 3062 3069 3076 3083
3090 3097 3105 3112 3119 3126 3138 3141 3148 3155
1
1
1
1
1
1 2 3 3
1 2 3 3
1 2 3 3
1 2 3 4
1 2 3 4
4
4
4
4
4
5
5
5
5
5
1 1 2 2 2 3 3 3
1 1 2 :I 2 3 3 4,
1 1 2 2 2 3 3 4,
1 1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
8 4
3
3
4
4
4
4
4
,4
1 1 2 2 3 3 4 4
1 2 2 3 3 4 4 Ii
1 2 2 3 3 4 4 5
1 2 2 3 3 4 4 Ii
1 2 2 3 3 4 4 Ii
1 2 2 3 3 4 5 5
"
2
2
2
2
2
2
2
2
3
3
4 5 II
4 5 8
4 IS 6
IS
5
5
6
6
6
6
6
6
6
456
Logarithms
"5
7'
11213141516171819
.50
.51
.52
.53
.54
3162 3170 3177 3184 3192 3199 3206 3214 3221 3228
3236 3243 3251 3258 3266 3273 3281 3289 3296 3304
3311 3319 3327 3334 3342 3350 3357 3365 3378 3381
3388 3396 3404 3412 3420 3428 3436 3443 3451 3459
3467 3475 3483 3491 3499 3508 3516 3524 3532 3540
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
4
5
5
5
5
5 6 7
5 6 7
5 6 7
6 6 7
6 6 7
.55
.56
.57
.58
.59
3548 3556 3565 3573 3581 3589 3597 3606 3614 3622
3631 3639 3648 3656 3664 3673 3681 3690 3698 3707
3715 3724 3733 3741 3750 3758 3767 3776 3784 3793
3802 3811 3819 3828 3837 3846 3855 3864 3873 3882
3890 3899 3908 3917 3926 3936 3945 3954 3963 3972
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5
5
5
5
6
6
6
6
7
7
7
7
.60
.61
.62
.63
.64
3981 3990 3999 4009 4018 4027 4036 4046 4055 4064
4074 4083 4093 4102 4111 4121 4130 4140 4150 4159
4169 4178 4188 4198 4207 4217 4227 4236 4246 4256
4266 4276 4285 4295 4305 4315 4325 4335 4345 4355
4365 4375 4385 4395 4406 4416 4426 4436 4446 4457
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
6
7
7
7
7
7 8
8 9
.65
.66
.67
4467 4477 4487 4498 4508 4519 4529 4539 4550 4560
4571 4581 4592 4603 4613 4624 4634 4645 4656 4667
4677 4688 4699 4710 4721 4732 4742 4753 4764 4775
4786 4797 4808 4819 4831 4842 4853 4864 4875 488
4898 4909 4920 4932 4943 495/? 4966 4977 4989 5000
1
1
1
1
1
2
2
2
2
2
3
3
3
3
4
4
4
4
3 5
5
5
6
6
.68
.69
6
7
7
7
5012 5023 5035 5047 5058 5070 5082 5093 5105 5117 1 2 4 5 6 7
5129 5140 5152 5164 5176 5188 5200 5212 5224 5236 1 2 4 5 6 7
5248 5260 5272 5284 5297 5309 5321 5333 5346 5358 1 2 4 5 6 7
5370 5383 5395 5408 5420 5433 5445 5458 5470 5483
4 5 6 8
5495 5508 5521 5534 5546 5559 5572 5585 5598 5610 ~ ~ 4 5 6 8
.75
.76
.77
.78
.79
5623 5636 5649 5662 5675 5689 5702 5715 5728 5741
5154 5768 5781 5794 5808 5821 5834 5848 5861 5875
5888 5902 5916 5929 5943 5957 5970 5984 5998 6012
6026 6039 6053 6067 6081 6095 6109 6124 6138 6152
6166 6180 6194 6209 6223 6237 6252 6266 6281 6295
6310 6324 6"389 6353 6368 6383 6397 6412 6427 6442
6457 6471 6486 6501 6516 6531 6546 6561 6577 6592
6607 6622 6637 6653 6668 6683 6699 6714 6730 6745
6761 6776 6792 6808 6823 6839 6855 6871 6887 6902
6918 6934 6950 6966 6982 6998 7015 7031 7p47 7063
.80
.81
.82
.83
.84
.85
.86
.87
.88
.89
8
8
8
8
I)
8 9
8 9
5 6 7 8 9
.70
.11
.72
.73
.74
6 7 7
7
8
8
8
910
910
910
910
8 9
810
910
910
910
11
11
11
11
12
1
1
1
1
1
3 4 5 7 8 9101 2
3 4 5 7 8 9 1112
3
7 810 1112
3
7 810 1113
3 4 6 7 910 1113
1
2
2
2
2
3
3
3
3
! Ig
3 4 6 7 910 1218
5
8 911 1214
5 ~ 8 9 11121 4
5 6 8 9 111314
5 6 810 11131 5
7079 7096 7112 7129 7145 7161 7178 7194 7211 7228 2 3 5 7 810 12131 5
7244 7261 7278 7295 7311 7328 7345 7362 7379 7396 2 3 5 7 810 1213 15
.90
.91
.92
.93
.94
7413 7430 7447 7464 7482 7499 7516 7534 7551 70682
7586 7603 7621 7638 7656 7674 7691 7709 7727 7745 2
7762 7780 7798 7816 7834 7852 7870 7889 7907 7925 2
7943 7962 7980 7998 8017 8035 8054 8072 8091 8110 2
8128 8147 8166 8185 8204 8222 8241 8260 8279 8299 2
8318 8337 8356 8375 8395 8414 8433 8453 8472 8492 2
8511 8531 8551 8570 8590 8610 8630 8650 8670 8690 2
8710 8730 8750 8770 8790 8810 8831 8851 8872 8892 2
.95
.96
.97
.98
.99
8913 8933 8954 8974 8995 9016 9036 9057 9078 9099
9120 9141 9162 9183 9204 9226 9247 9268 9290 9311
9333 9354 9376 9397 9419 9441 9~62 9484 9506 9528
9550 9572 9594 9616 9638 9661 9683 9705 9727 9750
9772 9795 9817 9840 9863 9886 9908 9931 9954 9977
2
2
2
2
2
3 5 7 910 1214 16
4 5 7 911 1214 16
4 5 7 911 13 14 16
4
4
4
4
4
6
6
6
6
6
7 911 13 15 17
8 911 13 15 17
8 10 12 14 15 17
810 12 14 16 18
8 10 12 14 16 18
4 6 810 12 15 1719
4 6 811 13 15 1719
4 7 911 13 15 1720
4 7 911 13 16 1820
5 7 911 14 16 18 2()
INDEX
A
~ldehyde
458
B
Babcock bottle, 384
Balance, analytical, 21
Barium hydroxide, 83
standard solution of, 83
Barium sulfate, determination of
specific gravity of, 220
Belladonna leaf, assay of, 416
extract, assay of, 415
fluidextract, assay of, 416
tincture, assay of, 414
Benzoin, assay of, 339
Block comparator, 299
Boiling points, 226
apparatus for, 234
method of determining, 235
table of official, 238
Boric acid, asslJlY of, 107
determination of pH of solution
of,287
of solubility in water, 205
Boyle's law, 189
Bromcresol purple, 73
Bromine, 0.1 N, 180
Bromphenol blue, 73
Bromthymol blue, 73
Buffer mixtures,,294
table of, 294
Buffer solutions, 293
solutions used to prepare, 293
Buffers, 67
'
Bunsen valve, 150
Burettes, 58
calibration of, 63
illustrations of, 59
official requirements ior, 59
reading of, 60
C
Caffeine, assay of drugs containing,
429
table of official substances assayed
for, 431
Calcium carbonate, assay of, 146
Calcium gluconate, assay of, 141
Calcium glycerophosphate, assay of,
48
Calculation of results and errors, 9
Calibration of weights, 26
IlY DEX
459
460
461
INDEX
Gravimetric methods, 37
assay of alum, 50
of calcium glycerophosphate, 48
of mercuric chloride, 45
of sodium chloride, 37
of sodium sulfate, 43
of solution of magnesium
citrate, 52
sample data for, 40
Grazing incidence, 241
Guarana, 429
H
J
Jalap, assay of, 440
K
I
462
Laevorotatory, 248
Laws, Boyle's, 189
Charles', 190
Dalton's, 198
Faraday's, 98, 306
Ohm's, 305
Limit test for chlorides and sulfates,
269, 270
Liquid petrolatum, determination of
kinematic viscosity of, 259
Liquids, transfer of, 19
Liter, normal, 58
Litmus, 74
Logarithms of numbers, 453
use of, 13
Lunge nitrometer, 194
Nature of errors, 9
Nephelometry, 260, 266
Nessler apparatus, 260
Neutralization methods, 65
buffers in, 67
pH value in, 66
theory of, 66
Neutralization reactions, 69
Nitrogen estimation, by GunningKjeldahl method, 98
with nitrates and nitrites absent,
98
with nitrates present, 99
Nitrometer, illustration of, 194
preparation and testing of, 195
Non-volatile ether-soluble extractive, 337
Normal conditions, 189
Normal liter, 42
Normal solution, 7(,-77
Normality, 77
Normality factor, 78
Notebooks,4
,.
Nux vomica, assay of, 425
M
Magnesia magma, assay of, 94
Magnesium, determination of, 52
Magnesium citrate, assay of, 52
Mass of ferrous carbonate, assay of,
153
Materials required, 7, 392
Mayer's reagent, 394
Measuring flasks, 61
Melting points, 226
apparatus for taking, 226
table of official, 230
Meniscus, 60
>to
Mercuric chloride, assay of, 45
~.!"
Mercuric potassium iodide, 394
Mercurous chloride, assay of, 166
Methenamine, assay of, 95
Methyl orange, 74
Methyl red, 75
Milliliter, 58
Moisture content, 329
Moisture limits of official substances,
333
Moisture tube, 332
Molal solution, 76
Molar solution, 76
preparation of, 185
Monochromatic light, 249
o
Official sample, 8
Ohm, 305
Oil of bitter almonds, assay for
benzaldehyde content, 373
assay for hydrocyanic acid, 379
of caraway, assay of, 375
of chenopodium, assay of, 380
of clove, assay of, 377
of mustard, assay of, 382
of orange, determination of refractive index of, 245
of peppermint, assay for total
esters, 366
assay for total menthol, 368
nephelometric estimation of,
269
Oleoresin of aspidium, assay of, 439
INDEX
Olive oil, iodine value determination
of,357
Opium, assay of, 418
table of official substances'assayed
by the same method as, 422
Optical activity, official substances
with requirements, 254
Optimum temperature of enzymes,_
444
Organic solvents, evaporation of, 400
Oxalic acid, 0.1 N solution of, 143
Oxidation, definition of, 130
Oxida tion-red uction, dichromate
methods, 151
table of substances assayed by,
154
direct titration methods, 136
table of substances assayed by,
140
iodometric methods, 155
standard solutions for, 132
methods, 155
theory of, 129
Oxide, official substances assayed by
ignition to, 51
P
Pancreatin, assay for casein digestive power, 449
for starch digestive power, 447
Parallax, effect of, 60
Partition coefficient, 391
Pepsin, assay of, 445
Permanganate methods, 133
pH, colorimetric methods of determining, 292
indicators and their use, 293
measurements, directions for, 29.6
meter, 291
potentiometric methods of determining, 277
relationship to voltage, 283, 284
value, 66
Phenobarbital, assay of tablets of,
441
Phenol, assay of, 181
463
464
Q
Quinhydrone, 288
Quinhydrone electrode, relation of
pH to voltage, 288
R
Reactions, in neutralization, 69
reversible, 30
Reagents, 6
Reduced iron, assay of, 137
Reduction, definition of, 130
Refractive index, 240
Refractive indices, determination of,
245
S
Salicylic acid, melting point determination o,"227
Samples, 'selection of, 7
drying and ignition'of,\19
Sampling, 7
Saponification value, definition of,
349
determination of, 349
official substances with limits of,
352
Saybold universal viscosity, 259
Sedimentation cone, 447
Separatory funnel, 388
Significant figures, 11
Silver nitrate, 0.1 N solution of, 117
Sodium arsenate, exsiccated, assay
of, 173
Sodium bicarbonate, assay of, 86
Sodium chloride, assay of, 37, 122
Sodium hydroxide, assay of, 87
normal solution of, 81
Sodium nitrite, assay of, 144
Sodium salicylate, assay of, 89
tablets, assay of, 108
Sodium sulfate, assay of, 43
INDEX
465
466
T
Tar~aric acid, assay of, 110
Test solutions, for alkaloids, 394
Theobromine with sodium salicylate,
assay of, 432
Xheophylline with sodium acetate,
assay of, 434
Thymol blue, 75
Thyroid, assay of, 170
Titer, 65
Titration, 78
curves, 285
direct, 86
potentiometrically, 281
residual, 86
Titrimetric methods, 57
Toluene moisture method, 331
Total ash, 323
Total esters, assay of oil of peppermint for, 364
Transfer of liquids, 19
Turbidimetric tests, 269
Type process, aliquot, 403
alkaloidal assays by, 403
general procedure, 394
Type process, total extraction, for
alkaloidal assays, 403
Units of capacity, 58
of electricity, 305
Unsaponifiable matter, 354
V
ViSCOSimeter, 258
ViSCOSity, definition of, 256
determination of, 259
units of, 257
Volatile ether-soluble extractive, 337
W
Wagner's reagent, 394
Wash bottles, 5
Water, determination of aIIJ.monia
content of, 261
Water-soluble extractive, 341
table of official substances with
limits of, 341
Wax, yellow, determination of specific gravity of, 222
Weights, calibration of set of, 26
description of, 25
Westphal balance, 216
use of, 217
X
Xylene moisture method, 331
z
Zinc oxide, assay of, 92