Henry W. (Henry William) Schimpf.

Essentials of volumetric analysis, an introduction to the subject, adapted to the needs of students of pharmaceutical chemistry, embracing the subjects of alkalimetry, acidimetry, precipitation analysis, oxidimetry, indirect oxidation, iodometry, assay processes for drugs, estimation of alkaloids, p online

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Online LibraryHenry W. (Henry William) SchimpfEssentials of volumetric analysis, an introduction to the subject, adapted to the needs of students of pharmaceutical chemistry, embracing the subjects of alkalimetry, acidimetry, precipitation analysis, oxidimetry, indirect oxidation, iodometry, assay processes for drugs, estimation of alkaloids, p → online text (page 18 of 24)
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* J. A. C. s., XVII, 828.


off the aqueous solution into a second separatory funnel.
Repeat this operation with two more portions of 15 mils of
acidulated water. Now^snder the contents of the separatory
funnel alkaline by adding ammonia- water. This liberates the
alkaloids, which are then separated by treatment with a mix-
ture of chloroform, three parts (by volume), and ether, one
part, using three successive portions, first 20 mils, then twice
1 5 -mils.

The chloroform-ether solution is heated on a water-bath
until the solvent is evaporated, and then the varnish-like
residue treated twice with 8 mils of ether and again evaporated.

The residue is then dissolved in 15 mils of alcohol, water
added to slight permanent turbidity, and then the indicator.
Titrate in usual way with decinormal acid and centinormal

A serious objection to this method lies in the taking of a
so-called aliquot part: First, because of the well-known solu-
bility of ether in water, and conversely of water in ether, as
a result of which the volume of the ethereal stratum is materially
changed. Furthermore, commercial ether contains variable
quantities of alcohol, hence the change in volume will not
always be the same.

Another source of error in the aliquot part is found in
the volatile nature of the solvents used. In warm weather
it is impossible to avoid loss by volatilization, hence the aliquot
part taken is too large.

W. A. Puckner *"Tias described a modification of the
Keller method which avoids the use of the aliquot part. He
uses only one-half of the ethereal solvent for the maceration,
and after the usual maceration transfers the drug to a small
percolator in which, after the ethereal solution has % been well

* Ph. Rev. XVI, 180, and XX, 457.


drained off, the marc is percolated with the same menstruum
to complete exhaustion. The quantity of ethereal solvent
required is not materially greater than in the Keller method,
while the quantity of alkaloid obtained for weighing or titrating
is larger because it represents the whole of the sample taken
for the assay. In the case of drugs containing a very small
proportion of alkaloid this is an important advantage.

The objection to this plan is that the transfer of the mass
from the flask in which the maceration has been conducted
to a suitable percolator, which should not be more than 3 cm.
in diameter, requires very 'dextrous manipulation, or it will
be attended with loss of alkaloid.

Assay of Galenical Preparations.

J. U. Lloyd's Method. One gm. of a solid extract which
has been dissolved in 5 to 8 mils of an alcoholic menstruum or
a corresponding volume of the tincture evaporated to this
bulk, or 5 mils of the fluid extract in a flat-bottomed porcelain
mortar, are mixed with 2 mils of a solution of perchloride of
iron. To this is added sodium bicarbonate with constant
trituration until a stiff magma * results. Extract this magma
by repeated trituration with chloroform, using first 20 mils
and then three portions of 10 mils each, decani ing them severally
by means of a 1 guiding-rod, being careful that no suspended
portions of the magma are drawn off. In order to make sure
that all of the alkaloid has been extracted, add 5 mils more of
chloroform, draw it off, evaporate on a watch-glass, dissolve

* The ferric hydroxid which is produced in the above process serves to
attract most of the tannates, gums, vegetable acids, and coloring matters,
while the excess of sodium bicarbonate liberates the alkaloids, which are then
dissolved by the chloroform. If the fluid extract is strongly alcoholic the
chloroform will not separate easily, in which case the addition of a few mils
of water containing a very little glucose will cause a sharp separation.


residue in dilute sulphuric acid, and test for alkaloids by
Wagner's or Mayer's reagent.

The mixed chloroformic extracts are collected and may be
estimated volumetrically as follows:

METHOD A. To be used if the chloroformic extract is not

The chloroformic solution is evaporated to dryness in a
flask placed on. a water-bath. To this residue is added an

accurately measured excess of sulphuric V.S. and the solution

diluted with a little water, the indicator added and the excess

of standard acid solution estimated by titrating with potas-

sium hydroxid V.S. The number of mils of the alkali V.S.


used, divided by 2 and subtracted from the volume of acid

V.S. originally added, will give the number of mils of the
latter required for the alkaloid. This number, multiplied by
the proper factor, will give the total alkaloid present in the
fluid extract.

Example. The chloroformic residue obtained from 5 mils
of a fluid extract of hyoscyamus was dissolved in 12 mils of


acid V.S., the solution titrated with - - alkali V.S. 20.6

25 50

mils of the latter were used.


20.6 mils of - - V.S. is the equivalent of 10.3 mils of


V.S. 10.3 mils subtracted from 12 mils, the amount of acid

1 N

originally adde'd, leaves 1.7 mils, the quantity of acid V.S.

which was required for the alkaloid. This, multiplied by the



factor for total alkaloids of hyoscyamus, 0.01157 gm., gives

the quantity of alkaloids present in the 5 mils, which quantity
multiplied by 20 gives the per cent:

1.7X0.01157 = 0.019669 gm.X2o = o. 39338 per cent.

METHOD B. This method may be employed if the chloro-
formic extract is highly colored, the indicator fluorescein being

The residue from the evaporation of chloroform is dis-
solved in 10 mils of acid-free alcohol; then water is added to

slight turbidity, followed by a measured excess of acid V.S.;


2 5

then the titration is completed with - alkali V.S. The first

appearance of fluorescence marks the completion of the reaction.

This is best observed by holding the flask over a dark surface
and viewing by reflected light.

METHOD C. This is to be used in the case of highly colored
extracts. It consists in removing the alkaloid in a pure state
by shaking out in a separating funnel with immiscible sol-
vents. The chloroformic extract is shaken out with several
portions of acidulated water; this removes the alkaloid, leaving
resins, fats, coloring matters, etc., in the chloroform. The
acid alkaloidal solution is then treated with ether in a second
separator, ammonia added to alkaline reaction, and the alka-
loid thus liberated by ammonia dissolves in the ether, from
which it is obtained by evaporation and estimated acidimetrically.

ANOTHER METHOD. Add ammonia and shake out directly
with an immiscible solvent. Wash the alkaloid out of this
with acidulated water and again shake out with a suitable
immiscible solvent.

J. Katz's Method (Arch. d. Pharm., 1898, i; Am. Dr.,
1 898 , 2 8 1 ) . This method has the advantage of all other methods


in that it enables one to rapidly and accurately estimate the
alkaloids in a preparation without the necessity of applying
heat for any purpose whatever during the process. The assay
may be made in from one to three hours. Twenty-five mils of
the tincture of an alcoholic strength of about 45 per cent are
placed in a separatory funnel, i mil of a 33 per cent solution
of soda added, and the mixture shaken for five minutes with
50 mils of ether, and set aside until the liquids have com-
pletely separated into two layers. The lower dark -colored
aqueous layer is drawn off into 'a beaker. The ethereal layer
which, besides the alkaloid, has taken up most of the alcohol
and some coloring matter, is shaken up with 3 mils of water
which, after separating, is drawn off and added to the first
aqueous liquid. The ethereal liquid is then poured into a
suitable flask, while the combined aqueous liquid is further
treated with two portions of ether (25 mils each) the ether to
contain about 10 per cent of alcohol. These ethereal extractions
are washed each with 1.5 mils of water; the first extraction
after washing may be added to the original ethereal solution,
while the second is reserved and later on employed for washing
the flask. The ethereal solution, which contains still some
traces of aqueous fluid containing alkali, is dehydrated by
treatment with 2 or 3 gms. of exsiccated calcium sulphate,
and finally filtered into a glass-stoppered flask containing 50

mils of water.

Titration by means of acid V.S. is employed, using

alcholic solution of iodeosin (1-250) as indicator.

The Method as above described is obviously applicable
only to such alkaloids as are readily soluble in ether. If an
estimation of alkaloids insoluble or only slightly soluble in
ether, but soluble in chloroform, is to be made, the method
is modified as follows:


Twenty-five mils of the tincture of 45 per cent alcoholic
strength are vigorously shaken for five minutes with 30 mils
of a mixture of i part of chloroform and 2 parts of ether. The
solution so obtained is washed with 3 mils of a 30 per cent
solution of sodium chlorid. This operation is repeated twice,,
using each time 15 mils of the ether-chloroform mixture and
washing with 1.5 mils of sodium chlorid solution.

If the Separation of the aqueous and ethereal liquids is not
distinct an additional 2 or 3 gms. of sodium chlorid may be
used. This prevents the emulsification, which, if pure water
were employed, would occur.

If the Tincture to be assayed contains more than 45 per
cent of alcohol it is necessary to add water to reduce it to 40
or 50 per cent.

Tinctures containing Chlorophyll or fat or fatty acids must
first be deprived of these constituents, as these substances,
possessing acid properties inferior to that of iodeosin, will act
the part of an alkali toward it and thus be recorded as alkaloid.

To remove the Chlorophyll and fatty acids, acidulate a
mixture of equal parts of the tincture and water with a few
drops of sulphuric acid, shake with talcum during several
hours, and, after subsidence of the latter, filter. Of this
filtrate 25 gms. (not mils, on account of the admixture of alco-
hol and water causing change of volume) are taken and the
alkaloid estimated in the manner already described, after
first removing, if necessar), the last traces of fat by a single
shaking of the acid solution with petroleum ether.

For the Assay of extracts i to 1.5 gms. are dissolved in
from 40 to 50 mils of 45 per cent alcohol to make a solution
containing less than 3 per cent extractive. For the assay of
fluid extracts 10 mils are taken.

For details of special assays, see the author's Manual of
Volumetric Analysis.


The Influence of the Presence of Certain Volatile Solvents

upon the accuracy of alkaloidal titrations must be borne in
mind. Alcohol in may instances influences the color changes
of the indicators to the extent of rendering them indistinct
or entirely unreliable; while ether or chloroform materially
diminishes the sensitiveness of many of our most valued
indicators, among them phenolphthalein, rosalic acid, Congo-
red, and luteol. On the other hand, fluorescein and gallein
may be mentioned as being more sensitive in the presence of
alcohol or even of ether. It is advisable, therefore, in most
cases, to perform the titration without the presence of the
above-named solvents.

Indicators Vary in their Degree of Sensitivenness to the
same Alkaloid, hence the choice of an indicator in a particular
case is a matter of importance. The following table, based
upon that of Kippenberger, will serve as an aid in the selection.
The smallest quantity which will procure a distinct tint should
be taken.

Atropine. Lacmoid, Fluorescein, lodeosin, Haematoxylin.

Brucine. Cochineal, lodeosin, Haematoxylin.

Cocaine. Lacmoid, Fluorescein, Cochineal, Haematoxylin.

Coniine. Cochineal, Lacmoid, lodeosin, Haematoxylin.

Codeine. lodeosin, Lacmoid, Haematoxylin.

Emetine. lodeosin, Cochineal.

Morphine. Hczmatoxylin, Cochineal, Lacmoid.

Quinine. Hcematoxylin, Azolitmin, Fluorescein.

Strychnine. Azolitmin, lodeosin, Haematoxylin.

Sparteine. Hcematoxylin , Azolitmin.



Preparation of Decinormal Bromin V.S. (Koppeschaar's
Solution), 61=79.92; 7.992 gm. in i liter.

KBr =119.02 NaBr =102.92
KBrO 3 = 167.02 NaBrO 3 = 150.92

This solution does not contain free bromin, but it contains
two salts, a bromid and a bromate, which, when treated with
hydrochloric acid, liberate a definite quantity of bromin.

It is made as follows: Dissolve 3 gms. of sodium bromate
and 50 gms. of sodium bromid (or 3.2 gms. of potassium
bromate and 50 gms. of potassium bromid) in sufficient water
to make 900 mils.

Transfer 20 mils of this solution by means of a pipette into
a bottle having a capacity of about ^250 mils, provided with a
glass stopper; add 75 mils of water, then 5 mils of pure hydro-
chloric acid, and immediately insert the stopper.

Shake the bottle a few times, then remove the stopper
just sufficiently to quickly introduce 5 mils of potassium iodid
solution (1-5), taking care that no bromin vapor escape, and
immediately stopper the bottle.

Agitate the bottle thoroughly, remove the stopper and
rinse it and the neck *of the bottle with a little water so that
the washings flow into the bottle, then add from a burette
decinormal sodium thiosulphate until the color of the free
iodin is nearly all discharged, then add a few drops of starch



solution, and continue the titration with thiosulphate V.S.

until the blue color disappears.

Note the number of mils of the sodium thiosulphate

thus used, and dilute the bromin solution so that equal volumes
of it and the sodium thiosulphate will exactly correspond

to each other under the above-mentioned conditions.

Example. Assuming that the 20 mils of bromin solution

required 25.2 mils of the thiosulphate to completely absorb

the iodin, the bromin solution must be diluted in the pro-
portion of 20 to 25.2; that is, each 20 mils must be diluted to
make 25.2 mils.

Thus if 850 mils are left, they must be diluted to make
1071 mils, and the solution is decinormal.

A new trial should always be made after diluting, and
the bromin solution should correspond, volume for volume,
with the decinormal sodium thiosulphate.

The first step in the preparation of this solution is to
dissolve the salts; then hydrochloric acid is added, which
liberates a definite quantity of bromin, as the equation illus-
trates :

5NaBr + NaBrO 3 + 6HC1 = 6NaCl + 3Br 2 + 3 H 2 O.

The stopper should be inserted into the bottle as soon
as the hydrochloric acid has been added, in order that no
bromin vapor escape, and the bottle rotated so as to mix the
acid thoroughly with the liquid.

The next step is to determine the quantity of bromin
which a definite volume of solution will liberate. The bromin
solution should be of such strength that 1000 mils of it will


contain 7.976 gms. of available bromin. Bromin, like chlorin,
liberates iodin from potassium iodid, and is estimated in
the same manner.

One atomic weight of iodin is liberated by one atomic
weight of bromin:

Thus by determining the quantity of iodin liberated the
quantity of bromin is found.

The iodin is determined by the - - sodium thiosulphate,

one liter of which represents 12.692 gms. of iodin, which is
equivalent to 7.992 gms. of bromin, as shown by the following
equation :

(Br 2 ) I 2 f 2(Na 2 S 2 O 3 + 5H 2 O)

20)159.84 20)253.84 20)496.44 N

7.992 gms. 12.692 gms. 24.822 gms. or 1000 mils V.S.

2NaI + Na 2 S 4 O 6 + ioH 2 O.

The Assay of Phenol. Dissolve i gm. of the sample in
sufficient water to make 500 mils of solution at the standard
temperature. Twenty mils of this solution containing 0.04 gm.
of the sample are transferred to a glass-stoppered bottle, having
a capacity of about 200 mils.

To this, 30 mils of decinormal bromin, followed by 5 mils
of hydrochloric acid, are added, and the bottle immediately
stoppered, and shaken repeatedly during half an hour.

Then the stopper is removed just sufficiently to introduce
5 mils of a 20 per cent aqueous solution of potassium iodid,
being careful that no bromin escape.

The bottle is then thoroughly shaken and the neck rinsed
with a little water, the washings being allowed to flow into the
bottle, then i mil of chloroform is added, the mixture thoroughly


shaken, and titration with decinormal sodium thiosulphate
V.S. begun, starch being used as indicator, until the blue color
is just discharged.

The precipitated tribromphenol interferes somewhat with
the end-reaction when starch is used, and frequently with
old phenol solutions * the precipitate possesses a bluish color
which is not removed by an excess of sodium thiosulphate and
which makes the end-reaction difficult. This difficulty is over-
come by the use of a small quantity of chloroform which dissolves
the tribromphenol and admits of a very sharp end-reaction.

When chloroform is alone used, the end-reaction is very
clearly denned, and is known by a colorless aqueous solution
and the chloroform being free from any tinge of pink, due to
traces of iodin.

Note the number of mils of thiosulphate used; deduct

this number from 30 mils (the quantity of bromin originally


added), and the quantity of bromin which went into com-
bination with the phenol is obtained.

Each mil of bromin represents 0.001556 gm. of pure


Example. Assuming that 6 mils of sodium thiosulphate

were required to discharge the color of the starch iodid, this
deducted from 30 mils leaves 24 mils, the quantity which
combined with the phenol.

0.001566X24=0.037584 gm.


= 93.96 per cent of pure phenol.

* F. X. Moerk, A. J. Ph., 1904, 475.


The above method originated with Koppeschaar, and is
the only volumetric method by which accurate results may
be obtained.

It is based upon the fact that bromin reacts with phenol,
producing an insoluble precipitate of tribromphenol.

The titration is not made directly; but the phenol solution
is treated with an excess of standard bromin solution in the
presence of some hydrochloric acid. The hydrochloric acid
liberates the bromin, and the freed bromin reacts with the
phenol, as shown by the equations:

(a) sNaBr + NaBrO 3 + 6HC1 = 6NaCl + 3H 2 O + 3Br 2

(b) C 6 H 5 OH + 3Br 2 - C 6 H 2 Br 3 OH

6)94 6)479.92

10)15.66 io)79-9 2 N

1.566 gms. 7-99 2 g m s. or 1000 mils bromin V.S.

Thus each mil of the - - bromin represents 0.001566 gm.

of pure phenol.

The bromin solution which was added in excess, and
the liberated bromin of which is not fixed by phenol, is then

found by residual titration with sodium thiosulphate after

the addition of some potassium iodid.

The decinormal bromin solution and the decinormal sodium
thiosulphate solution being equivalent, each mil of the latter
consumed represents one mil of the former. Then by sub-
tracting the number of mils of the sodium thiosulphate solu-
tion from the number of mils of bromin solution originally
added, the quantity of the latter which was actually consumed
by the phenol present is found. This number, when mul-
tiplied by the factor for phenol, then gives the quantity of
pure^phenol present.


The hydrochloric acid used in the above estimation must
contain no free chlorin. The potassium iodid must be free
from iodate. The starch T.S. should not be added until
most of the free iodin has been taken up, and the color of
the solution has diminished to light yellow.

The carbolic acid should be diluted with water before
titration, and should never be stronger than o.i gm. in 25 mils.

Resorcinol, C 6 H 4 (OH) 2 i : 3 (110.05). Dissolve about 1.5
gm., accurately weighed, in sufficient distilled water to measure
500 mils. Transfer 25 mils of this solution (representing 0.075
gm.) to a 5oo-mil glass-stoppered flask, add 50 mils of deci-
normal bromin V.S., and dilute with 50 mils of distilled water.
Then add 5 mils of hydrochloric acid and at once stopper
the flask, shake well, dilute it with 20 mils of distilled water,
add 5 mils of. potassium iodid T.S., let stand five minutes, and
then titrate the liberated iodin with decinormal sodium thio-
sulphate V.S., using starch as indicator.

Calculate as in preceding assay. Each mil of decinormal
bromin corresponds to 0.001834 gm. of C 6 H 4 (OK) 2 .

Phenylsulphonates, Sulphocarbolates. Dissolve about 0.25
gm. of the salt, accurately weighed, in 50 mils of distilled
water, add 50 mils of decinormal bromin V.S. and 5 mils of
hydrochloric acid. Allow the mixture to stand for fifteen
minutes, then add 2 gms. of potassium iodid dissolved in 5
mils of water, and titrate the liberated iodin with decinormal
sodium thiosulphate V.S., using starch as indicator.

Each mil of decinormal bromin V.S. used corresponds tc
0.04903 gm. of



The Acid Value or Proportion of Free Fatty Acids. This
indicates the number of milligrams of KOH required to neutral-
ize the free fatty acids in i gm. of oil, fat or wax. This standard

alkali used is in alcoholic solution and may be , , or weaker,

depending upon the nature of the fat. Phenolphthalein is the
indicator. The fat is dissolved, according to Geissler, in ether,
but alcohol or purified methylated spirit, chloroform or a mix-
ture of alcohol and ether may be used. The solverft, wh'chever
is used, must be free from acidity, and should be neutralized

with alkali if necessary.

The Process. Ten gms. of the oil are accurately weighed
into a flask and about 50 mils of solvent added. A few drops
of phenolphthalein are then added and the titration with


alcoholic - potassium hydroxid solution begun, shaking con-
stantly until the first appearance of a pink color. Care must
be taken not to add too great an excess of the alkali, other-
wise saponification will occur. A small excess may, however,
be added and retitrated with standard acid; a more distinct
end-point is then obtained. In the case of waxes or solid
fats, the solvent is added, heat applied until it boils, and the
titration at once started.



One mil of - KOH = 0.02805 gm. of KOH or 28.05 mgms.

The number of mils used, multiplied by 28.05 and then
divided by the weight of oil taken, gives the milligrams of
KOH neutralized by the free fatty acids of the oil, i.e., the
acid value.

The Saponification Value (Kottstorfer Number).* This
indicates the number of milligrams of KOH required for the
complete saponification of one gram of fat or oil. Reagents
required are:

Alcoholic Potassium Hydrfxid Solution, made by dissolving
40 gms. of potassium hydroxid in i liter of 95 per cent alcohol.

Half -Normal Hydrochloric Acid Solution. Each mil of
which = 28.05 m g m s. of KOH.

Indicator. Phenolphthalein i gm. in ieo mils of 95 per
cent alcohol.

The Process. Into an Erlenmeyer flask capable of holding
200 mils, accurately weigh about 1.5 gms. of the fat (previously
purified and filtered). Run into this from a burette 25 mils
of the alcoholic potassium hydroxid solution. Then insert
into the neck of the flask a perforated stopper provided with
a glass tube 70 to 80 cm. in length and from 5 to 8 mm. in
diameter, and set it in a water-bath for half an hour or until
the fat is entirely saponified. The operation is facilitated
by occasional agitation. The flask is then removed, its con^
tents cooled and titrated with the half-normal hydrochloric
acid, using phenolphthalein as indicator. The alcoholic potas^
sium hydroxid solution is standardized by conducting a blank
experiment similar in every detail to the above with the exception
that the fat is omitted.

* J. Kottstorfer, 1879, Zeitschr. anal. Chem., XVIII, 199.


The Kottstorfer number is then ascertained by subtracting
the number of mils of the standard hydrochloric acid used in
the analysis from the number necessary to neutralize 25 mils
of the alcoholic potassium hydroxid solution in the blank
experiment, multiplying the difference by 28.05 and dividing

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 18 20 21 22 23 24

Online LibraryHenry W. (Henry William) SchimpfEssentials of volumetric analysis, an introduction to the subject, adapted to the needs of students of pharmaceutical chemistry, embracing the subjects of alkalimetry, acidimetry, precipitation analysis, oxidimetry, indirect oxidation, iodometry, assay processes for drugs, estimation of alkaloids, p → online text (page 18 of 24)