AMERICAN
OURNAL of PHARMACY
SINCE 1825
Becord of the Progress of Pharmacy and the Allied Sciences
COMMITTEE ON PUBLICATION
arles H. LaWall, Ph. M.,Sc.D. Joseph W. England, Ph. M. J. W. Sturmer, Pharm. D.
on K. Thum, Ph. M. Arno Viehoever, Ph. D. E. Fullerton Cook. Ph. M.
IVOR GRIFFITH, Ph. M., Editor
Frederick B. Kilmer, Ph. M., Special Contributor
JULY, 1933
CONTENTS
itorials:
Apple Laundering
Wanted—A Leader
Original Articles:
A Simplified and More Efficient Method for the Extraction of Capsaicin
Together With the Colorimetric Method for Its Quantitative Deter-
mination in Capsicum Fruit and Oleoresin. By Linwood F. Tice, Phil-
adelphia, Pa.
The Identification of Cocaine and Novocaine (to be Continued). By Charles
Studies in Percolation, III. By Milton Wruble, Madison, Wis. ...........
The One Hundred and Eleventh Annual Commencement of the Philadel-
phia College of Pharmacy and Science
Medical and Pharmaceutical Notes
Book Review
Pri-e $3.00 per Annum in Advance Foreign Postage, 25 Cents Extra
Single Numbers, 30 Cents. Back Numbers, 50 Cents
Entered as Second-Class Matter at the Post Office at Philadelphia, Pa., Under the
Act of March 3, 1879
\cceptance for Mailing at Special Rate of Postage Provided for in Section 1103, Act of
October 3, 1917. Authorized February 15, 1920
PUBLISHED MONTHLY BY THE
Philadelphia College of Pharmacy and Scien
OF NATURA
43d Street and Kingsessing Avenue, West Philadelphia, re
JUL 29 1922
SF
i. 105 Pe No. 7
315
318
320
|
American Journal of Pharmacy
ESTABLISHED IN 1825
Four preliminary numbers were published at different times until in
1829, when the publication of the regular volumes began. Since then the
publication has been uninterrupted. During the period from 1829 to 1852
four numbers were published annually, except in 1847, when five numbers
were published. From 1853 to 1870 six numbers were published. Since this
time twelve numbers have been published annually.
Manuscripts should be sent to the Editor. It should be stated in this
connection that the Editor does not assume any responsibility in connection
with the views or investigations of contributors, other than to exercise gen-
eral care in the selection of matter.
Contributors are allowed a reasonable number of copies of this JouRNAL,
free of charge, if applied for when the proof is returned.
ReEprINTS, if desired, must be applied for when the proof is returned.
The table below shows the approximate cost of reprints, the make-up of the
pages to be identically the same as in the JourNAt. The actual cost may
vary from the figures given, and will depend upon the amount of presswork,
paper, binding, etc. Reprints containing half-tones may be expected to cost
somewhat more than the rates given.
CovERS WITH TITLES ‘ ’ 8 pp. 16 pp.
25 copies $1.75 $ 9.00
9.75
10.75
12.00
<=> Our readers will find it to their advantage to carefully consult the
advertising pages when desiring to correspond with STRICTLY
FIRST-CLASS PARTIES.
|
is
lack
his
appl
sene
tion,
dust
an
do
of
Sci
cry
col
| the
tra
plo
har
; less
and
Sap
is 1
| lear
||
|
THE AMERICAN
JOURNAL OF PHARMACY
VoL. 105 JuLy, 1933 No. 7
EDITORIAL
APPLE LAUNDERING
HE ancient adage
“An apple a day, keeps the doctor away”
antedated both the vegetarian vows of Fletcher and the drugless
dogmas of the Eddyists. Nor is it a slogan styled by an association
of enterprising fruit growers bent on making the world apple con-
scious. Rather it is the rhyming reaction of someone who long ago
crystallized in words the fundamental findings of an instinct-guided
countryside.
And proverbs of this wise are mostly dependable and true, al-
though they may not be nearly as euphonious or clever as are the
trade slogans of today, tempered to some special purpose.
Ever since Eve made the apple of Eden a symbol of lasting em-
ployment—and so slandered its services—the apple, in spite of such
handicap, is everywhere held in esteem.
It has furnished the healthy, healthful food and drink of count-
less generations. Young and old relish it and recognize its value—
and in its diversified kinds, from the sour crab to the succulent wine-
sap, democracy favors its flavor and finds it a form of insurance.
Yet the apple has recently come upon harrowing times. For man
is not the only creature with an apple appetite. Other insects have
learned to love it and the tree that gave it birth. No fruit tree today
is subject to such a variety of insect menaces as is the old apple tree.
‘No tree has been more inbred and altered, with a consequent
lack of resistance. Since the primitive Johnny Appleseed spread
his practical gospel over Ohio way—much change has come to the
apple—much improvement in flavor and texture, but a greatly les-
sened resistance. And to save his beloved fruit from insect extinc-
tion, man has had to resort to all manner of preventive sprays and
dusts and poisons.
(315)
ATURAL
or N
9
S Jur 29
OF
4
|
316 Apple Laundering { Am. Jour. Pharm.
Today it looks as if he has won a partial victory, even though
he continues to wage a tedious, torrid battle.
Arsenic, the far-famed poison of history, once the toxic tool of
courts and embassies, latterly gutterized to poison rats—has become
the successful weapon of defense in man’s fight for his precious apple.
And it is this wide use of arsenic in apple tree sprays that brings
our ancient adage back into the picture again—though with variation,
“An apple a day, may bring the doctor your way”
—except that fortunately, as usual, the lynx-eyed chemists of the
Federal force were quick to sense the danger and as quick to circum-
vent it. For of the arsenic used to kill the bugs much remained on
the skin of the apple—and was a potential danger to every consumer.
As high as a grain (a fatal dose) of arsenic has been reported
on a single apple, and one can only guess as to what damage was
done before the government insisted upon the thorough removal of
poison residues. This removal of arsenical residues is not a per-
functory, haphazard job. It must be thorough.
Today apples are forbidden in interstate sale if they contain
more than 1/100th of a grain of arsenic to the pound, a quantity obvi-
ously harmless. But how to dispose of these residues was the prob-
lem. And here is how the fruit of democracy is today made safe
for little Johnny; not particularly appetizing to read about, but at
least satisfying from a safety-first standpoint.
One method of washing involves the use of muriatic acid (1 per
cent. at 120 degrees F.), and another uses a silicate of soda at about
the same temperature, frothing of the bath being prevented through
the addition of kerosene. And this detergency must be complete, for
the oil sprays and the apple wax bind the arsenic quite firmly to the
skin.
Of course one finds it difficult to associate muriatic acid and
silicate of soda and kerosene with the time honored orchard comestible
—but better a laundered apple than an arsenic tainted fruit.
All of which suggests that the so-called forward march of our
civilization is often more of a retreat than a march, and always in
the face of tremendous odds.
We pollute our rivers with all manner of filthy sludge and sew-
age—and then proceed to remove the contaminants so as to secure for
our city-packed people, a drinkable Adam’s ale—well chemicalized in
the bargain.
l
|
t
I }
Apple Laundering 317
We grow a bumper crop of wheat full of things-of-the-sun—
we grind it and mill it and bleach it, and send most of its sunshine
away—just for the sake of elegance—a silly insistence on white—
while the less white whole wheat is far healthier.
Yet neither the pollution of our waters nor the bleaching of our
wheat is necessary.
Both are ridiculous!
But the apple laundering is another story. To make that friendly
fruit safe for democracy we must first foil the pests—even with as
dangerous a material as arsenic—and then find our safety in scrub-
bing—and scrubbing well.
But withal, we cannot refrain from suggesting that Galileo was
subtle when he murmured at his famous or infamous trial “E pur si
muove” (the world does move).
HE DID NOT SAY IN WHAT DIRECTION! !
Ivor GRIFFITH.
DIsTILLATION SEPARATES Light From Heavy WatTeEr-—Dis-
tiilation and adsorption can now be used to concentrate heavy weight
water out of ordinary water, Drs. Edward W. Washburn and Edgar
R. Smith, of the United States Bureau of Standards, have deter-
mined.
Electrolysis was the earlier method used by Dr. Washburn and
his associates to manufacture water heavier than normal. The com-
mon sorts of hydrogen and oxygen, masses I and 16, are given off
first as gases in electrolysis, leaving the remaining water rich in the
double weight hydrogen and the heavier oxygen isotopes 17 and 18.
Because the heavy water so made was found to have a higher
boiling point, Dr. Washburn realized that it should be possible to
fractionate water by distillation. He distilled ten quarts and the
two portions were found to differ in density by sixty-five parts per
million.
Water was also fractionated by allowing a mass of activated
charcoal to stand for three weeks in water. The adsorbed water
was denser than that unadsorbed.—Science News.
Wanted—A Leader {
WANTED—A LEADER
‘ty IKE a ship with an empty pilot house floundering in a fog” has
been tersely stated to be the condition of present-day pharmacy.
It is probably a fairly true statement; there is no one actually steer-
ing the ship.
Someone has said that we have “fallen apart into groups, classes,
blocks, sects and insects.” Manufacturers come together divided into
groups. Makers of chemicals, pharmaceuticals, proprietary and semi-
proprietary preparations, manufacturers of cosmetics and disinfec-
tants, makers of all sorts of compounds, wholesalers, chain stores,
syndicate stores, and dealers of many sorts form other classes and
groups; always one group separated from the others—sometimes di-
vided amongst themselves. We have in our calling no leaders, no
united front. In convention assembled we listen to spell-binding
oratory, pass resolutions, endorse legislations, and go home again.
Out of it there arise no leaders who lead. Even our splendid jour-
nals are not leaders. Among them are excellent specimens of modern
journalism and fine examples of the printer’s art, but they are so
numerous and so voluminous that we may fear that few “read, mark
and inwardly digest,” and that fewer still follow their teachings. We
have many, perhaps too many, writers—able, sincere, earnest gos-
pellers and preachers—but for the most part they are without fol-
lowers.
Perhaps we write too much, print too much, read too much and
do too little. Scholarship we have, and in truth we are making scien-
tific progress. Pharmaceutical education is advancing. But our schol-
ars, our professors, our men of high attainments are not born to be
leaders and they do not lead. Perhaps we have too many pharmaceu-
tical politicians, but are lacking in pharmaceutical statesmen. A
politician is defined as a man who puts his ear to the ground and
finds out what his constituents want and helps them to get it. On
the other hand, the statesman finds out what people really need and
helps them attain that need. We need leaders who are real leaders,
who do their own thinking and who can think in terms of the whole
realm of pharmacy. We need authority based on granite sound con-
victions, not on opinions or feelings.
“Pharmacy first” is a slogan that needs to be made the foun-
dation of every association, group or organization. It should be
318
I
I
a
I
1
O]
is
ar
Cit
in
in
of
pa
pe
We
Va
at
tin
lie
aci
Dr
“at Wanted—A Leader 319
written on the walls of every college, school and store and in the
hearts of every man who follows the calling. In our tragic and be-
wildering situation we need the authority of vision, knowledge, con-
viction and faith. We need men who not only see problems, but
see through problems; men who have not only sight, but insight;
men with open eyes and open hearts who see enough and are good
enough to be real leaders.
When a real leader is found he must have followers. Authority
must be recognized and obeyed. Localized group and self-interest
must be sacrificed for the good of the whole; else, progress will cease
and success will be impossible.
With courage, faith and hope we can emerge from the turmoil
and complexities which now encompass our calling. We may not
need a dictator, a Mussolini, a Hitler, or even a Roosevelt, but we do
need a leader who will lead.
Frep B. Ki_Mer.
TREATMENT OF VINCENT’Ss ANGINA—H. Downer in the course
of a paper on Vincent’s angina, states that the treatment of an attack
is the exhibition of arsenic combined with rest in bed. All forms of
arsenical preparations can be used, but the most convenient and effi-
cient is sodium cacodylate given hypodermically, at twenty-four hour
intervals, for a week or ten days. Local applications of arsenic are
invaluable, preceded by thorough cleansing with peroxide. The form
of arsenic again is of little importance, and liquor arsenicalis, B. P.,
painted on the infected areas is efficient and satisfactory. Sodium
perborate can take the place of peroxide of hydrogen, and a mouth-
wash of equal parts of liquor arsenicalis and ipecacuanha wine is of
value but will not reach ulcers on the tonsils or pharyngeal wall.
Treatment must be carried out at least after every meal and last thing
at night. If the cervical glands are enlarged and tender, antiphlogis-
tine compresses are invaluable. The pain in swallowing can be re-
lieved by aspirin or by a spray containing antipyrine and salicylic
acid—‘British Dental Journal,” 53, 9, 407, through Chemist and
Druggist.
320 Simplified Method for Extraction of Capsaicin ae
ORIGINAL ARTICLES
A SIMPLIFIED AND MORE EFFICIENT METHOD FOR
THE EXTRACTION OF CAPSAICIN TOGETHER
WITH THE COLORIMETRIC METHOD FOR ITS
QUANTITATIVE DETERMINATION IN CAPSICUM
FRUIT AND OLEORESIN
A THESIS
Presented to the Faculty of the Philadelphia College of Pharmacy
and Science
By Linwood F. Tice
Candidate for the Degree of B. Sc. (Pharmacy)
Isolation of Capsaicin
ARIOUS methods for the extraction of capsaicin, the active con-
stituent of capsicum, have been reported.' All of these methods
were found to be exceedingly tedious and time consuming or they
yielded a product which was highly colored and more or less impure.
A new method was devised which embodies certain steps in the
older methods but which is by far to be preferred, inasmuch as it
yields a snow-white crystalline product and the procedure is consid-
erably shortened.
The method of extraction is as follows:
I. Take approximately 100 gm. of oleoresin of capsicum (Mom-
bassa), place in a large separatory funnel and add 2 x its volume of
heavy liquid petrolatum. Shake well until thoroughly mixed.
II. Extract with three 200 cc. portions of 57 per cent. alcohol
and mix these extractions.
III. Add to this alcoholic extract 100 cc. of heavy liquid petro-
latum, shake well in a separatory funnel, allow to separate, and draw
off alcoholic layer.
IV. Distill off alcohol, cool and extract the aqueous liquid with
ether avoiding any loss of oily residue left in the flask which is ether
soluble. (Sodium chloride added to the aqueous portion will prevent
any troublesome emulsification encountered during this step.)
V. Evaporate the ether leaving an oily residue; add 4 gm. Li
(OH)» (carbonate free), 200 cc. water and boil for 10 minutes with
occasional stirring.
y, 1933
€
p
t]
el
(
di
et
et
re
gr
Am. Simplified Method for Extraction of Capsaicin 321
VI. Allow to stand over night, then pass in COg intermittently
for two hours, adding water if the liquid becomes too thick, and let.
stand over night.
VII. Filter through a Buchner filter, wash precipitate with water
and dry at a low temperature.
VIII. Place precipitate on filter into a large flask and boil with
500 cc. of petroleum ether for 15-20 minutes using a reflux con-
denser and occasionally agitating the material by rotating the flask.
IX. Pour the petroleum ether while hot through a filter paper
and set the clear filtrate in a sub-zero refrigerator over night to effect
crystallization. Reserve all undissolved material on filter for subse-
quent petroleum ether extraction.
X. Filter chilled petroleum ether quickly through a small plain
filter or a Buchner, collect crystals, dry, transfer to vial and tightly
stopper.
The precipitate (VIII) can be repeatedly extracted with the
same petroleum ether and the capsaicin subsequently crystallized out
by chilling. However, if the petroleum ether after repeated use
becomes markedly yellow, it should be discarded and a fresh lot sub-
stituted ; otherwise, the crystals yielded will be faintly colored.
The filter paper and funnel used in IX should be saved, covered
with a glass plate, and used to filter successive hot petroleum ether
extractions.
Employing the above method and starting with 100 gms. of
Mombassa oleoresin at least 5 gm. of capsaicin should be obtained,
providing several extractions of the precipitate (VIII) are made.
A brief explanation of the steps is as follows: The heavy liquid
petrolatum serves to withhold much fixed oil and coloring matter,
then by distilling off the alcohol and extracting with ether any water
soluble materials are eliminated. The “oily” liquid left after the
ether evaporation is impure capsaicin which when boiled with Li
(OH). solution forms a water soluble lithium capsaicin. This is
decomposed and capsaicin is precipitated in crystals by the action of
COs. Then the dried precipitate is extracted with hot petroleum
ether in which it is somewhat soluble, and upon chilling the petroleum
ether, its solvent power decreases ; thus capsaicin crystallizes out.
The capsaicin obtained by this process gave all the identity tests
reported and was found to possess a sharp melting point of 64 de-
grees C,
322 Simplified Method for Extraction of Capsaicin { Am-jour. puarm.
Attention is called to the extreme pungency of capsaicin (1-10,-
000,000 detectable in throat) and although it is not volatile the small
crystals are so fluffy that they are carried mechanically into the air
upon the slightest disturbance. Therefore, capsaicin in crystalline
form should be transferred from one container to another under a
hood or violent sneezing and coughing will result.
The Colorimetric Assay
The reaction of capsaicin with vanadium oxytrichloride was re-
ported by Fodor * who outlined a brief method for the assay of the
capsaicin content of capsicum based on this reaction. A study of his
method was made for the purpose of adapting it for use on cap-
sicums many times more pungent than those used in his experiments.
Certain changes and refinements have been made which enable one
to satisfactorily employ this method to supplant the unscientific or-
ganoleptic tests which are quite inaccurate, realizing the inconsistency
of taste in a quantitative determination.
The assay is of a colorimetric nature depending upon the reaction
of vanadium oxytrichloride (VOCl3) with capsaicin producing an
intensely’ blue compound vanadyl capsaicin,
(Fodor). The absence of water must be maintained throughout, us-
ing dry chemicals and apparatus, as water destroys the vanadium
salt and densitizes the color reaction.
The following substances should be available:
1. Vanadium oxytrichloride C. P.—This should be kept in small
bottles with greased glass stoppers in a desiccator.
2. Carbon tetrachloride C. P.
3. Dried Acetone—Dried over CaCl and distilled.
4. Paprika—Free of pungency.
5. Capsaicin—This can be readily obtained by the process given.
It should be a white crystalline solid with a sharp melting point of
64 degrees C.
The drug is assayed by first obtaining a representative sample.
If the drug be whole, this is not difficult ; if it be ground care should
be taken in sampling not to collect either all fine portions, which con-
sist largely of placentae and contain most of the activity, or all
coarse particles, which consist of seeds and pericarp, and contain but
little.
a} Simplified Method for Extraction of Capsaicin 323
The sample is preferably dried over night in a desiccator. A 2
per cent. w/v extraction of the drug is made by macerating the drug
from 30 to 60 minutes with dry acetone in a stoppered flask with occa-
sional agitation. If the oleoresin is to be assayed a 0.2 per cent.
solution of the oleoresin is made in dry acetone.
A solution of the active principle is now prepared 0.02 per cent.
in dry acetone, colored by extracting sufficient capsaicin-free paprika
to produce a color depth approximating that of the 2 per cent. extract
of the drug to be assayed. The use of a dried acetone w/v extract
of paprika as the solvent in preparing this standard was found to
result in a closer matching of the unknowns with the standards, the
reason being that the VOCls reacts with the coloring principles of
both capsicum and paprika similarly. The amount of paprika needed
will vary between 0.I per cent. and 0.2 per cent. depending upon the
amount of color in the capsicum to be assayed.
A series of standard tubes are prepared by measuring from a
burette the correct quantity of the 0.02 per cent. solution of cap-
saicin in colored acetone and diluting to 5 cc. with colored acetone.
The standard tubes are prepared by the following chart:
0.02% capsaicin Capsaicin content
in colored acetone Colored acetone of standard tube
1.5 cc. 3.5 cc. 0.006%
2.0 cc. 3.0 cc. 0.008 %
2.5 cc. 2.5 cc. 0.010%
3.0 cc. 2.0 cc. 0.012%
3.§ cc. 1.5 cc. 0.014%
4.0 cc. 1.0 cc. 0.016%
4.5 cc. 0.5 cc. 0.018%
5.0 cc. o 2, 0.020%
The standards are put in a rack in sequence and are immediately
followed by the tubes containing the unknowns. Beginning with the
first of the standards one drop of a I per cent. solution by volume of
VOCIs3 in CCl4 is added to each tube for each thousandth of a per
cent. of capsaicin known to be present using an ordinary medicine
dropper to add the reagent. The reagent is then added to the un-
knowns, carefully, drop by drop, until no deepening in blue color is
noticed. If an excess of reagent is added the liquid turns green and
cannot be matched with the standards as the color is not of the same
324 Simplified Method for Extraction of Capsaicin
quality. Consequently, it is advisable to take several tubes of the
same unknown and add a different number of drops in each and
then select for matching the tube having the greatest depth of blue
but no suggestion of green. When experience is obtained this pro-
cedure will not be necessary as the worker soon learns when a suffi-
cient amount of reagent has been added to the unknowns. The re-
agent must be added to all tubes both standards and unknowns with-
out appreciable time elapsing between the additions as the color
slowly fades after its production. To add the reagent to the stand-
ards and then in 15-20 minutes to the unknowns would invalidate the
analysis.
The unknown tube having the greatest depth of blue is now
matched with the standards and that standard found which has the
nearest color depth to it. In cases where the unknown tube lies be-
tween two standards it is assigned a value correspondingly—e. g., an
unknown tube darker than 0.010 per cent. and lighter than 0.012 per
cent. would be given a value of 0.011 per cent. This increases the
accuracy of the determination.
The matching is best accomplished by looking down through the
tubes at a source of diffused illumination such as a frosted incan-
descent bulb.
A flat bottom 10 cc. glass tube with an internal diameter of about
II mm. provides the best tube to be used for the work. A matched
set for height of 5 cc. was obtained and used in this study.
After estimating the per cent. capsaicin in the unknown tube,
this figure is multiplied by the dilution factor 50 in case of the drug,
and 500 in case of oleoresin. This results in the per cent. capsaicin
present in the sample.
If the sample produces an unknown tube falling either below
or above the standards in intensity of color, repeat the assay using
a higher or lower concentration of the sample in acetone, instead of
preparing lower or higher standards, as it is difficult to compare color
depths lower or higher than those of the standards given.
Several varieties of capsicum were assayed and the capsaicin
content found to vary over wide limits from less than 0.1 per cent.
to as much as 1.0 per cent. It was also found that within a single
variety there is considerable fluctuation. Mombassa capsicum was
found to be unquestionably superior to all others in capsaicin content
both in the drug itself and the oleoresin prepared from it.
It was definitely verified by the colorimetric examination of cap-
sicum that the placenta contains the preponderance of the active prin-
Am ¢ Simplified Method for Extraction of Capsaicin 325
ciple, as has been previously reported. The cortex contains only a
small amount and the seeds practically none.
Oleoresins made by extraction of capsicum with carbon tetra-
chloride were shown to be decidedly inferior to those made by the
use of acetone or ether. Such oleoresins not only were subject to
rapid color deterioration but they also were deficient in capsaicin
content. The use of metallic apparatus in conjunction with carbon
tetrachloride is particularly deleterious to capsaicin, and copper seems
to be the worst offender in this respect.
It was observed that vanadium oxytrichloride reacts with various
other phenols. It is suggested that some interesting experiments
could be conducted to attempt the utilization of the vanadium method
in the assay of phenols other than capsaicin.
Summary
1. A more satisfactory technique for the isolation of capsaicin
is presented,
2. The details of the vanadium colorimetric assay method for
the capsaicin content of capsicum are outlined, and
3. Some observations made during this study of general interest
concerning capsicum are included.
BIBLIOGRAPHY
(1) Thresh—Pharm. Jour. and Trans, 1876, iii, 7, 21, 259, 473. Micko—
Zeits. f. Unters. d. N. u. Genussm., 18908—818. Nelson—J. Ind. & Eng. Chem.,
1910—419. Lapworth & Royle—J. Amer. Chem. Soc. (Trans.) 1919—1100.
(2) Zeits. f. Unters. d. Lebensm., Sept. 26, 1930.
Identification of Cocaine and Novocaine on <<
THE IDENTIFICATION OF COCAINE AND
NOVOCAINE
(To be continued.)
By Charles C. Fulton
Associate Chemist, United States Industrial Alcohol Laboratory,
Minneapolis, Minn.
HE laboratories of the U. S. Industrial Alcohol Bureau examine
samples of illegal cocaine seized by the Narcotics Bureau. Dur-
ing the last two years or so a large part, perhaps most, of this co-
caine has been adulterated with novocaine. There have also been
cases of complete substitution of novocaine for cocaine. Novocaine
is not subject to the Federal law which regulates the sale and pos-
session of the alkaloids of opium and coca leaves. It is therefore
necessary that the government chemists be able to identify both co-
caine and novocaine separately and also be able to prove beyond
question the presence of cocaine in mixtures of the two. Others
may be interested in the tests for these alkaloids, and in the discus-
sion of general precipitation methods which are applicable to all
amines.
Tables of Precipitation
The two following tables give pictures of the relation of cocaine
and of novocaine to the alkaloidal precipitating agents. The sensi-
tivities are stated and the reagents giving crystals are underlined.
General information about the reagents, and the exact formulas
for most of those used in this study, will be found in my article
“The Precipitating Agents for Alkaloids.” *
Explanations of Tables
The reagents giving crystals are underlined. Only amorphous
precipitates have been observed with the others, but it is probable that
crystals can be obtained in a few other cases by special treatment,
such as warming.
The arrangement of the reagents in columns, and the numbers
attached to each, pertain to the sensitivity as compared with that of
phosphomolybdic acid. Starting with the strongest solution of the
alkaloid a series of solutions was prepared by repeatedly doubling the
volume of a part of the solution. The last solution of this series to
(1) American Journal of Pharmacy, April, 1932.
]
(
(
S
L
I
P
M
Zi
St
Bi
M
B
Gi
Ta
Ldentification of Cocaine and Novocaine
COCAINE
(ALKALorpD DissoLveD In DituTe Acetic Acip)
(Or HyprocHLoriIDE IN NEUTRAL WATER)
strongest solution about
solution 1, about 1 :2500 5%, soln. 128
Phosphomolybdic acid—1 Nessler’s—2 Conced. KI—128
Phosphotungstic acid—1 Silver Na Iodide—z 5% KI—no ppt.
Silicotungstic acid—1 Zinc K Iodide—16 Nickel Na Thiocyan.—32
Bromine in NaBr—% Reinecke’s Salt—2 NH4SCN—128
Bromine in HBr—% Cobalt Na Thiocyan.—4 Concd. FeClg—128
Bromine water—4 Cadmium Na Thiocyan—8 BiCls in HCIl-—32
Wagner's No. 1—1/16 Ferric Na Thiocyan.—2 SbClz in HCI—32
Wagner s No. 4—1/16 Manganous Na Thiocyan—7nC], & HCIl—128
Wagner's No. 6—% 4 to 8 CdClo & HCl—no ppt.
Wagner’s No. 8h Stannous Na Bromide, acidZince chloride—no ppt.
odine Mercuric bromide—16, 8 Saccharin—no ppt.
HgBrez in HCI—4 p-Nitrophenol—32
Maree’ HgBre in NaBr soln—4 _—Picrolonic acid—no ppt.
mayer Cadmium Na Bromide—8 KoCroO07—64
Coned, Mayer's—% Platinum Bromide—4 Perchloric acid—16 to 32
Mayer’s & KI—¥Y4 :
to Platinum bromide _& HClNa Perchlorate—32 to 16
Cadmium iodide—1 Potassium chromate—128
Stannous Na Iodide, acid—% Mercuric Na Chloride—4 Concd. K Acetate—no ppt.
Na lodide— Chloromercuric acid—4 NazHPO.,—no ppt.
Lead Na ide—Y Mercuric chloride—16 Na Nitroprusside—64
acid-—% HgCls in HCl—16 K Ferricyanide—128
_ in NaCl sola.—16 K Ferrocyanide—no ppt.
NaI—1 Platinum chloride—16 Mercuric Na Nitrite—128
Platinum Na Thiocyan.—¥% Platinum chloride & HClNa Cobalti-Nitrite—32
Mercuric K Thyocyan.—1 iil Lead Copper Sodium Nitrite
Na Palladium _chloride—16 —no ppt.
Stannic chloride in HCl—16 Lead Na Nitrite—no ppt.
Gold Bromide—%4 SnCl2 in HCl—16
Gold bromide & HCI—% FeCl; in HCI—8
Bismuth bromide in HBrPicric acid—z2
Na Picrate—4
Mercuric Na Bromide—¥2 “Pannic acid—8
Bromomercuric acid—%
Gold Chloride__¥ Alizarin Na Sulfonate—16
Gold Chloride & HCI—-1 to_/tinitroresorcin—4
Molybdate—4
Tonic acid & NaAc—1 Na_ Phosphomolybdate—&
Chromic anhydride—16
Concd. CrOs—8
CrOs & HCIl—4
CrOzg in NaCl soln.—4
KMnO.—about 8 to 16
Sodium carbonate—4
Sodium hydroxide—8
Ammonia—8&
Potassium cyanide—8
Gold Cyanide—8
Platinum Cyanide—-4
Mercuric Na Chloro Nitrite —8
327
Identification of Cocaine and Novocaine { Am. Jour. Pharm.
July, 1933
NOVOCAINE (HyprocHioripE In WATER)
strongest solution about
1:16, soln. 512
Acid Wagner’s No. 8—64
Acid Mayer’s & KI—256
Nessler’s—32
Acid Marme’s—512
Stannous Na Iodide, acid—
solution 1, about 1 :8000
Wagner’s No. 6—2
Wagner’s No. 7—4
Wagner’s No. 8—8
Acid Wagner’s No. 3—2
Acid Wagner’s No. 5—16
Iodine-NaBr—4
Iodine in Excess NaBr—16
Phosphomolybdic acid—1
Phosphotungstic acid—1
Silicotungstic acid—1
Bromine in NaBr—%4
Bromine in HBr—%
Bromine water—%
Wagner’s No. 1—%
Wagner’s No. 3—%
Wagner’s No.4—1 to %
Wagner’s No. 5—1I to 2
Acid Wagner’s No. I—%
Dragendorff’s—¥% to I
Dragendorff’s & KI—1 to 2
Mayer’s—1 to %
Concd. Mayer’s—'%
Gold Bromide—1
Bismuth Bromide in HBr—
Gold Chloride—1
(with short standing;
32
Silver Na Iodide, acid—128
Zinc K Iodide—256
Concd. KI—512
5% KI—no ppt.
Acid Zinc Na Thiocyan.—64
Cobalt Na Thiocyan.—64
Lead Na lodide—: Cadmium Na _Thiocyan.—64
Silver Na a ee Acid Cobalt Na Thiocyanate
: —no ppt.
Antimony K Iodide, acid—84-iq Cadmium Na Thiocy-
Platinum Iodide & Excess nate—no ppt.
1p Na 1-4 to 8 Ferric Na Thiocyan.—128
Platinum Na Thiocyanate—2Njcke] Na Thiocyan.-—256
Platinum Na Thiocy-\anganous Na. Thiocyn.-
anate—4
Acid Mayer’s—4
Mayer’s & KI—8
Marme’s—8
Cadmium lodide—16
128
immediately, 2 quickly)
Reinecke’s Salt—16
Mercuric K Thiocyan.-—8
Stannous Na_ Thiocyanate,
acid—128 to 256
Acid Mercuric K
nate—16
Zinc Na Thiocyanate—8
Gold Bromide
immediately, 2 gradually
Mercuric Na Bromide—4
Bromomercuric acid—16
Mercuric Bromide—16
Gold Chloride
& HCl—16
HgBr2 & HeSO4—no ppt.
HgBre & HCl—no ppt.
HgBre in NaBr_ soln—32
to 64
Stannous Na Bromide, acid
—no ppt.
Cadmium Na Bromide—64
acid withPlatinum Bromide—128 im-
H2SO4—8 immediately, 2_ mediately, 16 gradually
gradually
Picric acid—16
Tannic acid & NaAc—8
NH4 Molybdate—16
Platinum Bromide & HCI—
no ppt.
Gold Chloride & HCl—512
Mercuric Na Chloride—32
Conced. CrOs—64 immediate-Mercuric chloride—64
ly, 16 soon, 8 gradually
HgCle in NaCl soln—128
Chloromercuric acid—128
HgCle in HCl—no ppt.
Platinum chloride—256 im
mediately, 64 gradually
Platinum Chloride & HCI—
no ppt.
Palladium Chloride—32
SnCl4 in HCl—no ppt.
SnCle in HCl—no ppt.
FeCls in HCl—no ppt.
BiCls in HCl—no ppt.
SbClz in HCl—no ppt.
ZnCle in HCl—no ppt.
328
SO
us
an
Ne)
be:
ho
are
july, 1933 t Identification of Cocaine and Novocaine 329
CdCle in HCl—no ppt.
Zinc chloride—no ppt.
Cadmium chloride—no ppt.
Na Picrate—32
Trinitroresorcin—64
Tannic acid—no ppt.
Picrolonic acid—no ppt.
Alizarin Na Sulfonate—64
(acid, 64 also)
Na Phosphomolybdate—64
Na Molybdate—no ppt.
Chromic anhydride—512 im-
mediately, 64 gradually
KeCre07—256
CrOs & HCl—128 soon, 64
gradually
CrOxz in NaCl soln.—64 grad.
Perchloric acid—no ppt.
Na Perchlorate—256
Sodium carbonate—64
Ammonia—64
Sodium hydroxide—64
Potassium cyanide—128
Potassium chromate—no ppt.
Concd. K Acetate—no ppt.
NazHPO4«—no ppt.
Gold Cyanide—64
Platinum Cyanide—64
Na Nitroprusside—128
K ferricyanide—256
K ferrocyanide—no ppt.
Mercuric Na Chloro-Nitrite
—64
Mercuric Na Nitrite—128
Lead Copper Sodium Nitrite
—no ppt.
Lead Na Nitrite—no ppt.
Na Cobalti-Nitrite—no ppt.
give an unmistakable precipitate with phosphomolybdic acid is called
solution 1. It contains the unit quantity of alkaloid per unit volume,
using phosphomolybdic acid precipitation as a standard. The next
stronger solution contains twice as great a concentration of alkaloid
and is called solution 2; the next stronger after that is solution 4.
Similarly the solutions of the series beyond the limit of distinct pre-
cipitation with phosphomolybdic acid are labelled 14, 4%, and so on.
The number accompanying a reagent in the table shows the last
solution in which it gives a distinct precipitate. The smaller the num-
ber, therefore, the more sensitive the reagent: the number shows
how many “phosphomolybdic acid units” of the particular alkaloid
are required for precipitation.
330 Identification of Cocaine and Novocaine ~~ a
In making these sensitivity tests, let fall one full drop of reagent
from a I cc. pipet into a drop of the alkaloidal solution of equal or
only slightly greater size. Usually I make three such tests on the
ordinary microscope slide. The light must be such that one can see a
very finely divided precipitate. The crystal tests are, in general, also
made with a full drop of reagent.
When precipitation falls off quite gradually with dilution there
may be some doubt as to which solution is the last one yielding a
distinct and unmistakable precipitate. However this margin of doubt
is never so great as to seriously diminish the value of the scheme.
Classification is based primarily on a consideration of which reagents
equal or exceed phosphomolybdic acid in sensitivity and which are
markedly less sensitive.* This is easily ascertained; when necessary
a direct comparison should be made on adjacent slides between the
reagent in question and phosphomolybdic acid.
In the first column of each table are listed the reagents that
equal or exceed phosphomolyhdic acid in sensitivity toward that al-
kaloid; in the second column those that are less sensitive, but still
precipitate with no more than 16 phosphomolybdic acid units; and
in the third column the remaining reagents.
“Within the columns the reagents are written in the following
order (1) Complex Oxygen acids, (2) Halogen reagents, (3)
Iodides, (4) Thiocyanates, (5) Bromides, (6) Chlorides, (7) Or-
ganic reagents, (8) Simple oxygen acids, and salts of oxygen acids,
(9) Basic reagents, (10) Cyanides, (11) Nitrites. This corre-
sponds roughly to the general precipitating ability and sensitivity of
the principal and better-known reagents of each group.
The Cocaine table reports the precipitation of cocaine acetate, pre-
pared by dissolving the free alkaloid in dilute acetic acid. Substan-
tially the same values have been found when using solutions of co-
caine hydrochloride in water, in tests made both by myself and by
Mr. Garvey of this laboratory.
In general it is the best practice to use the acetate of the alka-
loid, with a slight excess of acetic acid, for such tests. This gives
more scope for the comparison of neutral and strongly acid reagents
than if a strong acid such as sulfuric is used. Hydrochloric acid in
excess is out of the question, as it would greatly affect the sensitivity
of most of the chloride reagents and some of the others; even the
(2) Fulton: The Identification of Alkaloids by Precipitation. Jour. A. O.
A. C., XIII, 4, page 491 (1930).
a
r
P
p
it
Cl
b
ta
ag
lo
K
ne
Sel
in
ea
ta
fo
an
Th
in
Sco
for
nee
do
: und
july. i933," Identification of Cocaine and Novocaine 331
small amount present when the hydrochloride of an alkaloid is used
will sometimes noticeably affect the sensitivity and crystallization with
such reagents as HgClo, HgBro, and mercuric sodium nitrite.
The Novocaine table reports the precipitation of the hydro-
chloride, the usual commercial salt.
Solution I, as noted at the top of the tables, has for cocaine a
concentration equivalent to about I gram per 2500 cc., for novocaine
about I gram per 8000 cc. Phosphomolybdic acid and corresponding
reagents are therefore more sensitive, on an absolute scale, to novo-
caine. This absolute scale has to be considered in determining the
possibility of detecting one alkaloid in the presence of another by
precipitation. In general however the relative scale is more useful.
Using the relative scale, as is done in the columns of the tables,
it will readily be seen that cocaine and novocaine belong to different
classes and that cocaine is much more easily precipitated, as is shown
by the greater number of reagents in the first column of the cocaine
table.
It will be observed that the standard Wagner’s and Mayer’s re-
agents are more sensitive than phosphomolybdic acid to both alka-
loids, but that when such reagents contain a considerable excess of
KI their sensitivity toward novocaine declines to solution 8 (Wag-
ner’s No. 8; Mayer’s & KI), while with cocaine they remain more
sensitive than phosphomoloybdic acid. This is an important point
in classification: alkaloids that resemble novocaine in this respect are
easily distinguished from those that resemble cocaine.
Another class-characteristic which is quite marked and impor-
tant in the case of novocaine is its lack of sensitivity to strongly acid
forms of numerous reagents, particularly halide reagents containing
an excess of the halogen acid, as for instance Gold chloride & HCl.
This is utilized in obtaining crystals for the identification of cocaine
in the presence of novocaine.
Crystalline precipitates are of course examined under the micro-
scope. Low power is usually adequate. Characteristic crystals serve
for the identification of the alkaloids.
Descriptions of Cocaine Crystals
Stannous sodium Iodide, acid. Rosettes of delicate branching
needles. Crystals form fairly readily in concentrated solutions and
down to solution % at least; sensitive to I :20000.
Lead sodium Iodide. Minute crystals, little rods in thin rosettes
under high power. Test has no practical value.
332 Identification of Cocaine and Novocaine a ee
Platinum Iodide in excess NaI. Two kinds of crystals form
gradually from the amorphous precipitate; small square grains or
platelets in solution 8 and more dilute; rosettes of threads in more
concentrated. Crystallization is incomplete and the test has little or
no practical value. Compare with the following.
Silver sodium Iodide. Crystals of good size form gradually
from the amorphous precipitate. They are of two kinds. In the
more dilute solutions, or with sufficient excess of reagent, irregular
long plates, thick and grain-like, but transparent and colorless or
very slightly yellowish, or colorless stick-like crystals, form in thin
rosettes ; best in solutions 4 and 8, especially if two drops of reagent
are used. In solutions more concentrated than 16 dense dark rosettes
of needles or threads are formed; these crystals are a peculiar shade
of brown. Test sensitive to about 1:600. An acid form of the re-
agent is made by adding 2 drops of diluted sulfuric acid (1+3) to
I cc.
Gold Bromide (Brom-auric acid). Feathered crystals, small
needles, and splinters, often in thin rosettes or branched a little. Sen-
sitive to solution 1/16, or about 1 :40,000.
Gold Bromide & HCl.* Similar to the preceding; crystals more
needle-like, less feathery. Equally sensitive.
Stannous sodium Bromide, acid. Usually forms rosettes of
branching threads, or branching twigs. Sensitive to solution 2, or
about 1:1200. (This reagent is made by adding 4.5 gm. NaBr to
10 cc. of the same Stannous chloride stock solution used for making
Stannous sodium iodide, acid.) The type of crystallization is some-
what variable.
Platinum Bromide (Bromo-platinic acid). Feather-comb-crys-
tals quickly form from the amorphous precipitate. They have con-
siderable resemblance to the well-known crystals with Platinum
Chloride and constitute one of the best tests for cocaine. Charac-
teristic crystals obtained down to about I :1000.
Platinum Bromide & HC1.* Similar to the preceding; crystals
more comb-like, less feathery. Almost equally sensitive.
Gold Chloride (Chlor-auric acid).* Crystals form gradually
from the amorphous precipitate; branching needles, small feathery
crystals, and some comb-like crystals. Gold Chloride & HCl is better.
_ Gold Chloride & HCI.* Crystallizes readily; small needle-like
branching crystals form from the amorphous precipitate and grow
to fairly large thin comb-like crystals with the teeth at an angle. There
may also be rosettes of needles branching across each other. Easily
sensitive to solution %, or I :20,000.
Platinum Chloride (Chloro-platinic acid). This is generally
considered the principal test for cocaine. Immediate crystallization
*These reagents contain 25 per cent. by volume of concentrated HCl.
(3) The crystals with these reagents are described and pictured by Steph-
enson in Some Microchemical Tests for Alkaloids. (Lippincott, 1921.)
july.i933 dentification of Cocaine and Novocaine 333
in feather crystals, growing coarser and more comb-like on standing.
Characteristic crystals obtained down to about I :500.
Platinum Chloride & HCl.* Similar to the preceding, but the
crystals are somewhat larger, thinner, and more comb-like. Sensi-
tive to about 1:300 (solution 8).
Palladium Chloride (Chloro-palladous acid).* Crystallization is
slow and rather uncertain. Dense rosettes of needles form in con-
centrated solution, or with stirring. Addition of a littke HCI or
NaCl assists crystallization while diminishing the sensitivity. Crys-
tals then vary to salmon-colored rods, which form in concentrated
solution. Stephenson’s reagent may have differed a little from mine,
but in any case the test has little or no practical value.
Stannic Chloride in HCl. Crystals form readily ; fair-sized ros-
ettes of glassy crystals and small glassy grains. This test has a
practical sensitivity of about 1:200, though small crystals form
gradually down to 1:600. It is a very good test for cocaine.
Stannous Chloride & HCl. Crystals form gradually from the
amorphous precipitate; large rosettes of branching needles. The
test has no great value as crystallization is slow and it is difficult to
keep the reagent without having the tin go over to the stannic form.
Ferric Chloride in HCl. Large splinter, blade, and fern-like
crystals quickly form from the amorphous precipitate in solutions
128 to 16. There may be some rosettes of needles and splinters. The
precipitate has some tendency to dissolve in more dilute solutions,
although crystals can be obtained in solution 4, particularly if two
drops of reagent are used. The practical sensitivity is at least I :200.
An excellent test.
Concentrated FeCl solution (1:1). Large splinter crystals
form, solutions 128 to 32. Similar crystals described and pictured
by Stephenson were obtained from concentrated solution with 5 per
cent. ferric chloride.*
Antimony Chloride & HCl. Crystallization is incomplete, but
in concentrated solutions, 128 and 64, some large glassy grains are
formed.
Picric acid.* The amorphous precipitate crystallizes slowly in
large dense rosettes of thin needles or threads.
Sodium Picrate. Crystals the same as with picric acid, but form
more readily. They form gradually in solution 2, slowly even in
Solution I (1:2500).
Trinitroresorcin. The amorphous precipitate crystallizes slowly,
or with stirring, in dense rosettes of needles or threads.
Alizarin sodium Sulfonate. The precipitate gradually crystal-
lizes in brown rosettes of needles, solutions 128 to 16. Sensitive to
about 1 :150.
*These reagents contain 25 per cent. by volume of concentrated HCl.
(3) The crystals with these reagents are described and pictured by Steph-
enson in Some Microchemical Tests for Alkaloids. (Lippincott, 1921.)
334 Identification of Cocaine and Novocaine
Chromic anhydride. The precipitate given by the 5 per cent.
reagent usually does not crystallize, although rosettes of threads can
be obtained by stirring and seeding. Concentrated CrO3 solution
usually gives large rosettes of threads, but even with it crystalliza-
tion is uncertain, and crystals may fail to form even on stirring.
CrO3 & HCl.* The amorphous precipitates, particularly in
the more dilute solutions, usually yield splinter crystals, and branch-
ing needles in large growths more or less circular. Crystallization
is a little uncertain.
CrO; & NaCl. The amorphous precipitate usually yields branch-
ing needles or threads in large growths, often rosettes.
Perchloric acid. The amorphous precipitate crystallizes in either
of two ways: either it forms dense rosettes of needles or threads;
or else it forms large colorless angular plates, and branching crystals.
Sodium Perchlorate gives practically the same results.
Potassium Permanganate (slightly acid).* Crystals are best
obtained by adding just a small drop of the 5 per cent. reagent with
a stirring rod. Solutions 128 to 4 then give crystals, mainly square-
cut reddish-lavender-colored plates. Only a few alkaloids give sta-
ble crystalline permanganates; therefore the test is a good one for
pure cocaine; sensitive to about 1:600. Oxidizable impurities gener-
ally destroy the test. If the reagent is added as a full drop of I per
cent. KMnO, there are obtained in addition to the plates both
branching crystals and small, rather dark rosettes.
Basic Reagents. NasCOz, K KCN, NH,4OH, and NaOH precipi-
tate free cocaine. The precipitate is amorphous but will generally
crystallize, on stirring, in rods or peculiar floating branching forms.
The precipitate with NaOH redissolves in the more dilute solutions,
due to hydrolysis. NagCOg is a little more sensitive than the others,
but perhaps KCN and NH,OH give a little readier crystallization.
Crystals to about 1:300. The crystals are described by Stephenson,
but not pictured.
Sodium Cobalti-Nitrite. Yellow rods in rosettes form in the
most concentrated solutions (128 and 64).
Descriptions of Novocaine Crystals
Bromine in HBr is the best bromine reagent; Bromine in NaBr
and Bromine water give similar crystals but not so readily. Crystal-
lization takes place best in concentrated solution but crystals are ob-
tained down to solution 8 (1:1000). The crystals are white and are
generally rosettes of branching needles or threads. Transparent
irregular flakes or plates are also formed.
Mayer's & KI, In concentrated solutions white opaque round-
ish lump crystals grow out from a center of crystallization in rosette
*These reagents contain 25 per cent. by volume of concentrated HCI.
(3) The crystals with these reagents are described and pictured by Steph-
enson in Some Microchemical Tests for Alkaloids. (Lippincott, 1921.)
tals.
ette:
tals.
thre.
Cryst
Witl
(1
imm
Plati
gives
with
solut:
cal t
(
Large
istic ;
down
partia
A
fz
I
to
pa
in
SiS
ros
tat
shc
fo
sol
the
&
ette
ter
mot
may
—— =} Identification of Cocaine and Novocaine 335
fashion. There are also some splinter-plate crystals. Solutions 512 to
128 crystallize in a short time ; on standing crystals are formed down
to solution 32 (1:250).
Lead Na Iodide (2 drops). Good crystallization; small trans-
parent rods, formed down to solution 2 (1:4000).
Gold Bromide. Amorphous precipitate, crystallizing gradually
in small to minute orange-yellow plates, often in rosettes. HCl as-
sists crystallization and makes the crystals larger. (See following.)
Gold Bromide ¢» HCI.* Small orange plates, scattered and in
rosettes. Solutions 512 to 16 give an immediate amorphous precipi-
tate which soon crystallizes completely. Solutions 8 to 2 do not
show immediate precipitation, nevertheless an amorphous precipitate
forms first and crystallizes gradually. Crystals can be obtained in
solution I on standing (1:8000). The best crystals are obtained near
the limit of immediate precipitation (about 1:500).
Mercuric Na Bromide. Results similar to those with Mayers
& KI. Concentrated solutions (512 to 64) crystallize in opaque ros-
ettes in which the individual crystals seem to be small grains. Splin-
ter-like crystals may also form. Crystals will form in somewhat
more dilute solutions with stirring; or on standing the precipitate
may slowly yield grains.
Mercuric Bromide. The precipitate gradually forms grain crys-
tals.
Bromomercuric acid. Long branching needles in sheaves or ros-
ettes. Sensitive to solution 16 (about I :600).
HgBrz in NaBr solution. Forms plate-rods and branching crys-
tals. Sensitive to about 1:150.
Cadmium Na Bromide. Crystallizes in branching root-like and
thread crystals, or in rod-plates.
Platinum Bromide (Bromoplatinic acid). Probably the best
crystal test for Novocaine. Small dark rosettes of needles form soon.
With a little standing they are readily found down to solution 4
(1:2000). If only a very small drop of reagent is used there is
immediate crystallization in light colored feathered crystals (See
Platinum Chloride).
Gold Chloride acid with HySO4. Although gold chloride itself
gives only an amorphous precipitate, when rather strongly acidified
with sulfuric acid there is partial crystallization from concentrated
solutions in small grain-plates in groups or rosettes. Not a practi-
cal test.
Gold Chloride & HCl.* One of the best tests for Novocaine.
Large, irregular, coarsely feathered yellow plates, very character-
istic and easily recognized. With a little standing they are formed
down to solution 32 (about 1:250).
Mercuric Na Chloride. A concentrated solution will crystallize
partially, on stirring, in grains.
*These reagents contain 25 per cent. by volume of concentrated HCl.
336 Identification of Cocaine and Novocaine A™- Jonr.
HgClz in NaCl solution. With stirring gives crystals readily;
grains and long slender rods, the latter often in rosettes. Sensitive
to solution 32 (about 1:250).
Chloromercuric acid. Crystallizes mainly as fairly large slender
rods, many in rosettes and sheaves. Grains may also form.
Platinum Chloride. If only a very small drop of reagent is added
with a stirring rod there is immediate crystallization in bushy feath-
ered crystals, irregular plates, etc., the precipitate having consider-
able resemblance io that of cocaine. If however a full drop of re-
agent is added there is immediate crystallization only in concentrated
solution. Solutions 512 to 256 give coarsely feathered plates some-
what yellow in color, and other feathered crystals similar to those
of cocaine. Following this crystallization, in solutions down to 64 a
yellow amorphous precipitate forms, and from this form gradually
dark round crystals or dark rosettes that are aggregates of grains.
The test with a minimum of reagent is sensitive to about I :60, while
the dark rosettes are obtained down to about I :125.
Palladium Chloride. Sphero-crystals form. They may become
rosettes of thin rods. Sensitive to solution 32 (about 1:250).
Picric acid. Large branching splinter crystals and curved branch-
ing crystals form slowly from the amorphous precipitate in concen-
trated solutions, or on stirring. Crystals can be obtained down to
solution 8, or 1:1000, but as with cocaine crystallization is some-
what uncertain.
' Na Picrate. Readier crystallization than with the acid. Fern-
like rosettes form slowly; or with stirring there is complete crys-
tallization, mainly in fern rosettes, with some long irregular yellow
plates. Sensitive to solution 32 (about 1:250).
Trinitroresorcin., Crystallizes readily and completely, with three
kinds of crystals in the same solution; good-sized needles in rosettes,
yellow “smudge rosettes” (smaller), and quite small grain-platelets.
Microscopically all the crystals are yellow. Sensitive to solution 64
(1:125).
Potassium Dichromate. The precipitate crystallizes slowly, or
on stirring, in large thick grain-sticks, orange.
Gold Cyanide. The precipitate soon crystallizes completely and
densely in fern-like plates. With stirring crystals are obtained down
to solution 16, about I :500.
Mercuric Na Chloro-Nitrite. With stirring, the most concen-
trated solution gave partial crystallization in colorless transparent
prisms. Both Mercuric Nitrite reagents give white precipitates that
soon turn yellow—a color test.
Cocaine—General Properties
1. Cocaine is methyl-benzoyl-ecgonine. It is usually sold and
used in the form of the hydrochloride.
i
1]
t
a
b:
he
fc
| m
ca
tes
re
all
ve
tes
coc
age
che
H
july, 1933 } Identification of Cocaine and Novocaine 337
appearance of which has given cocaine the nickname “snow”. Free
cocaine is a white crystalline solid.
2. Appearance. The hydrochloride (although it also occurs as
large crystals) is usually in the form of glistening white flakes, the
3. Solubility. ‘The hydrochloride is very soluble in water. Adul-
teration by such substances as phenacetin or acetanilid is at once
observed by their failure to dissolve readily. The free base is insolu-
ble in water but dissolves readily in dilute acids, and is soluble in the
common organic solvents and in petroleum ether.
4. Odor on solution. Cocaine hydrochloride on dissolving in
water gives off a pleasant odor, slight but distinct. This test is not
.mentioned by any of the authorities, so far as I know. A narcotic
agent called it to my attention.
5. Physiological effect. Applied to the tongue it causes tingling
and numbness, and a curious smooth feeling of the anaesthetized
part. Mulliken gives specific directions for the test.*
6. Extraction. Cocaine is not removed from acid solution by
immiscible solvents but is readily extracted from basic solution. Car-
bonate or ammonia should be used, never strong alkali, or the cocaine
will be hydrolized. Extraction with petroleum ether will separate
it from many alkaloids.
7. Melting point and volatility. Free cocaine melts at less than
the boiling point of water (at 98 degrees, according to Mulliken) ;
and enough wil! sublime between two watch-glasses on the water
bath for detection with gold chloride.
8. Hydrolysis. Cocaine is hydrolized very readily by alkali on
heating. Methyl alcohol, the benzoate of the alkali, and ecgonine, are
formed. Concentrated acids will also cause hydrolysis, forming
methyl ester of the acid, benzoic acid, and a salt of ecgonine. Co-
caine must not be warmed or let stand in alkaline solution or there
will be little or no cocaine left as such.
Direct Chemical Tests (aside from microscopic tests)
1. Color tests. None of any value, except insofar as the four
tests following can be called color tests. Most reagents for color
reactions (Froehde’s and Marquis’ reagents, etc.) give no color at
all with cocaine. Concentrated nitric acid is perhaps the most con-
venient reagent for discovering admixture or adulteration by a color
test.
2. Potassium permanganate retains its purple color in acidified
cocaine solution. Those adulterants or substitutes that are reducing
agents discharge the color.
3. Mercurous nitrate solution, used to moisten the solid hydro-
chloride, yields a dark gray. The reagent used was made with concd.
HNOs—I0 cc. water—go cc. mercury in excess. This is a far bet-
(4) Mulliken: Identification of Pure Organic Compounds.
O
y
S.
14
or
1
1d
Vn
=nt
yal
nd
338 Identification of Cocaine and Novocaine { Am- Jour. tuarm.
ter form of the test than triturating the cocaine hydrochloride with
calomel and moistening with 90 per cent. alcohol, as is directed by
several text-books. Novocaine hydrochloride gives the same test.
(This is really a reagent test, depending on the formation of metallic
mercury, while the two preceding are negative tests. Strictly only the
following tests are direct chemical tests for cocaine.)
4. Phosphotungstic acid, added to the solution on the spot-plate,
gives a pure white precipitate. Numerous other alkaloids do like-
wise, but many, including novocaine, give precipitates tinted pink,
salmon, orange, or yellow. A 10 per cent. solution of phosphotung-
stic acid, not containing any nitric acid, is used.
5. Cobalt sodium thiocyanate gives a blue precipitate from
acidified solution. Although actually a precipitation test, this has
the effect of a color test as the reagent solution is pink. The best
method for the test, I think, is to dissolve a convenient quantity of
the sample, on the spot-plate, in one drop of diluted sulfuric acid
(1+3), and add one drop of cobalt sodium thiocyanate solution.
Cocaine gives a blue precipitate. From neutral solution novocaine
also gives a blue precipitate, but with the acid its solution will re-
main clear and will simply be colored pink by the reagent. There
are, to be sure, many alkaloids that behave like cocaine in this test.
A test of this nature was originally given by Mr. Young of the
Washington laboratory of the Industrial Alcohol Bureau.°
6. Sticking test. Wagner’s reagent, and picric acid, applied to
the solution on the spot-plate, yield heavy precipitates which form a
varnish-like coating on the plate, and stick so tightly that they cannot
be cleaned off by washing and rubbing with a towel. (The picric
acid precipitate however may crystallize on standing.) Novocaine
gives the same test. An alkali, or mineral acid, or alcohol, will clean
the plate.
7. Borax test. When a drop of 0.5 per cent. borax solution is
added to some solid cocaine hydrochloride (best on the microscope
slide) solution is immediately followed by the formation of a white
precipitate which soon crystallizes, generally in rods. This test is
due to Mr. Ryan of the Washington laboratory of the Industrial
Alcohol Bureau.
Derivative Tests
1. Benzoic acid. Add NaOH in excess to a cocaine solution,
and heat. Add some alcohol, if necessary to hold the cocaine in solu-
tion until hydrolyzed, and later evaporate it off. Hydrolysis is com-
plete when an acidified drop of aqueous solution gives no precipitate
with gold chloride. On acidifying the hydrolyzed solution benzoic
acid is set free. It is not very soluble in cold water and will be
precipitated if the solution is at all concentrated. It can be detected
(5) James L. Young, in Am. Jour. Pharm., 103, 709 (1931). C. A., 26, 1063.
july, 1933 Identification of Cocaine and Novocaine 339
even though very little cocaine was present by shaking out the acid
solution with ether. The ether is separated and shaken with dilute
ammonia, which is then evaporated to dryness on the water bath.
The ammonium benzoate is then taken up in a little water and a drop
or two of nearly neutral ferric chloride solution added. A flesh col-
ored precipitate of ferric benzoate results.
Vitali’s test gives an odor test for the benzoyl group. Dis-
solve the cocaine in concentrated nitric acid on a watch-glass, evap-
orate to dryness on the water bath, cool and add alcoholic KOH.
The odor of ethyl benzoate can then be noted, but it disappears
quickly if the quantity of cocaine was small.
A simpler procedure is to dissolve the cocaine in a little alco-
holic KOH, warm, and pour into a few cc. of water, and note the
odor of ethyl benzoate.
2. Ecgonine. This is the most important and characteristic
product of the hydrolysis of cocaine, and is the basic or amine part.
When the benzoic acid is extracted by ether from the acidified solu-
tion the ecgonine remains in the water, in which it is quite soluble.
(In fact, it cannot be extracted from aqueous solution.) It is read-
ily identified by its precipitates from dilute acid solution with various
alkaloidal reagents. The best tests are probably those with Dragen-
dorff’s reagent and gold bromide. Dragendorff’s reagent (preferably
the double-strength form) gives two different types of crystals, de-
pending on the temperature. One type, formed on the hotter days,
or in warm solution, consists of large orange plates which when
separate and perfect are octagonal. The other type consists either of
orange-red hexagonal plates, or dark red six-pointed stars. Gold
bromide (brom-auric acid) gives red square platelets, generally
pretty small.
(To be continued)
)
ly
e
Cc
d
3.
Studies in Percolation he Pharm.
uly, 1933
STUDIES IN PERCOLATION*
III
By Milton Wruble
(Continued from the June Issue.)
2. Romershausen’s “Luft”- and “Dampf-Presse”
As has been shown, Réal’s “‘filtre-presse” represents an adaptation
of the pressure filter * to Dubelloy’s cafetiére.? Originally intended,
in part at least, for the extraction of ground coffee with water, the
pressure was attained by means of a column of water. Inasmuch
as pressure was regarded as of the essence of the apparatus, the
higher the column the more perfect the extraction. However, the
height of the water column proved a practical inconvenience. Hence,
a column of mercury, the density of which is 13.6 times greater than
that of water, was substituted. While this substitution enabled a
greater compactness of the apparatus, the increased pressure thus
made possible, necessitated a corresponding strengthening thereof.
Moreover, the inconvenience of the spilling of mercury because of
insufficiently tight joints had to be taken into consideration. The
application of the apparatus to pharmaceutical extractions with
alcohol in no way lessened the difficulties and inconveniences en-
countered when Réal’s press was introduced into the apothecary’s
laboratory.
Apparently it was Kastner, who appears to have been interested
in apparatus producing air pressure, and who suggested, as early as
1818, that a “Luftpresse’” might supply the pressure as well as a
column of water or mercury.* It was Romershausen who acted
upon the suggestion, had his apparatus patented and described them
in a pamphlet published in 1818. Judging from the attention given
the new apparatus in contemporary pharmaceutical literature, the
modification was well received. Marechaux, in 1821, refers to the
supposed improvement in the following words:
“Gewoehnlich gelangt der Geist auf Irrwegen zum Ziel, das
Einfachste findet er zuletzt. Wie leicht war es nicht, das lange Rohr
der Realschen Presse zu verkuerzen, und _ vermittelst eines
Drukkolbens, was schon mit allen hydraulischen Pressen geschah,
denselben Zweck zu erreichen, den man vermittelst Queksilber, oder
*Madison Pharmaceutical Experiment Station.
A
340 |
I
ri
P
ay
th
m
nit
the c
Cloth
Clasp
cylin
provi
sectic
vide
belo
july, 1933 t Studies in Percolation 341
Luftcompressions-Apparate zu bewerkstelligen suchte. Dem Doktor
Rommershausen blieb das Verdienst vorbehalten, die einzige Ein-
richtung vorzuschlagen, welche geeignet seyn konnte die Realsche
Presse ins Leben einzufuehren.
In the numerous modifications of his apparatus, Romershausen
applied pressure in three different ways:
1. By compressing the air above the menstruum, thus forcing it
through the comminuted material.
2. By creating partial vacuum in the receiver, thus sucking the
menstruum through the comminuted material.
3. By forcing steam through the material to be extracted.
His apparatus were manufactured for use in the brewing, tan-
ring, dyeing and pharmaceutical industries.
Fig. 1—-ROMERSHAUSEN’S AIR PRESS.
The two tin cylinders B and C are mounted on the support A, and are provided with
the covers 1 and 10. On the support the diaphragm 3 is placed, covered with a straining
cloth which is held in position by the diaphragm 4, which in turn is fastened by the
clasp 5. A third diaphragm 6 is used to cover the substance to be extracted. The two
cylinders are united by the tube 7 provided with a stopcock. The lower part of B is also
provided with a stopper at 8 in order to allow the percolate to flow out at 9. The lower
section of C is converted into an airtight compartment by the cover 11, which is pro-
vided with an opening and stopper at 12. The parts indicated by 13, 14, 15, 16 and 17,
belong to the suction pump necessary to create a vacuum.
Apert fd Pharma B VE
2 Tob
1
PoP 0.0 feos =
00% 2} \ |
oo
4)
| >
B. c
§
2 3
+
2 |
|
@)
342 Studies in Percolation
Inasmuch as Romershausen’s original pamphlet is not available,
we are dependent for our information on articles in pharmaceutical
and other journals based on this publication.
During the same year in which Romershausen published his
pamphlet, Trommsdorff called attention to Romershausen’s improve-
ments of the Réal press, but gives no illustrations of the apparatus.’
In the same year Buchner also gave a brief account of the improve-
ment, but does not illustrate the device.®
A third account is that by Kastner,® who classifies Romer-
shausen’s “Luftpressen” into three groups, viz. :
1. Those intended for domestic use (coffee, etc.).
2. Those intended for apothecaries, which he designated
“Tincturmaschinen” and constructed of five sizes.
3. More elegant apparatus for “the coffee and tea table.”
The first illustrated journal article appears to be that by Buchner
of the same year.’°
Fig. 2—-ROMERSHAUSEN’S MODIFIED AIR PRESS.
The suction pump is outside of the cylinder and the percolate is not allowed to col:
lect underneath the percolator B, but is at once pumped into the reservoir C.
(
I
t
il
n
a
as
sc
T
pt
ha
co
nu
cet
C
ai B
| |
4
a
j
t>
AF
Fi
Fig
Fig
Studies in Percolation 343
In the same year, Romershausen, in a letter to Trommsdorff,
discusses pressure percolation as carried out by means of his ap-
paratus and points out its adaptation to pharmaceutical practice.™
In 1822 Romershausen published a historical account of ex-
traction presses.” While some of his contemporaries praised his
improvements over the Réal apparatus, Parrot concluded after a
number of experiments that pressure extraction was unnecessary
and that ordinary extraction with the aid of a screw press was just
as effective provided that the material to be extracted was first
soaked with the menstruum and allowed to stand prior to expression.'*
To this Romershausen took exception claiming that Parrot’s inter-
pretation of the experimental results were faulty; also, that if he
had used Romershausen’s press he would not have reached his
conclusions."*
It has been pointed out that Romershausen manufactured a
number of styles and modifications of his air press. Of modifica-
tions by others, that by Beindorf was given publicity in the pharma-
ceutical press.
Fig. 3—BEINDORF’S MODIFICATION OF ROMERSHAUSEN’S AIR PRESS.»
Figs. 3 and 4—Simpler and more compact types.
Fig. 5—This apparatus is supplied with an extra supply of menstruum in vessel c.
Fig. 6—A graduate for measuring liquids.
ral
ff
C¥ Igs
344 Studies in Percolation
All of the apparatus described are provided with suction pumps
creating a partial vacuum underneath the powder to be extracted,
thus producing atmospheric pressure from above. Romershausen’s
first method of applying pressure from above does not appear to
have received consideration in the apparatus described in pharma-
ceutical and other scientific journals. His third method found ap-
plication in his “Dampfpresse.” Apparatus of this type were de-
scribed by Marechaux. One of these is herewith reproduced.’®
Darr
ooo
Fig. 4#-ROMERSHAUSEN’S “DAMPFPRESSE”’.*
The water warmed in the reservoir, is heated so that the steam generated will force
it upward through the material “M” to be extracted, the extract to be collected in the
“Sammlungs-gefaess’”’.
In closing this survey, it may be pointed out that Beindorf’s
suggestions received attention in contemporary texts and even some-
what later, viz., in
Buchner, Einleitung in die Pharmacie (1822), p. 247.
Geiger, Handbuch f. Pharmacie, Bd. I (1830), p. 141.
Doebereiner, Deutsches Apothekerbuch I (1842), p. 79.
Imperfect as this account of the second phase of percolators
may be, it shows that, as interest in Réal’s invention seemed to
wane, the further study of percolation received a stimulus through
Romershausen’s inventions. In connection with the story of Réal’s
apparatus and modifications thereof by others, it has been pointed
out that the subject of percolation entered a new phase when the
Boullays, pére et fils, developed the process without pressure. In
2
|
4 |
>
|
Cotas
a Studies in Percolation 345
this connection, attention should once more be directed to the claim
made by Professor Parrot of Dorpat as early as 1823, viz., that
pressure applied in the percolator was unnecessary, indeed that a
special percolator was uncalled for since, by proper treatment, the
same results could be obtained by using an ordinary screw press.
This criticism, however, leaves out of consideration the phase of
displacement which is so important in the process of percolation.
Hence, when the excitement of novelty due to Romershausen’s in-
ventions was over, the idea of pressure percolation appears to have
been abandoned for a time, at least so far as pharmaceutical opera-
tions are concerned.
REFERENCES
1. See Réal’s “Filtre-presse” and its “Modifications,” footnote 2, this jour-
nal, p. 290. See also Cadet: “Les Anglais ont fait une application de cet prin-
cipe a la purification des huiles.” Journ. de Pharm. 8 (1816), p. 165.
2. Dubelloy’s cafetiére.
3. Column of mercury first proposed by Réal (Journ. de Pharm. 8 (1816),
p. 166), was later applied by Trommsdorff (Journ. der Pharm. 25, II (1816),
P. 47).
4. Berl. Jahrb. f. d. Pharm. 20 (1819), p. 392. Kastner’s original suggestion
was made in the Deutscher Gewerbsfreund, 1818, edited by him. Unfortunately,
this journal is not available. Hence Prof Kastner’s words may here be quoted:
“Im ersten Hefte des dritten Bandes . . . meines D. Gewerbsfreundes machte
ich auf eine frueherhin schon von mir in Vorschiag gebrachte . . . Extrac-
tions-Saugpumpe . . . und ueberhaupt auf die Anwendung der Luftpumpen
Einrichtung auf verschiedene Gewerbe aufmerksam . . .; nach einiger Zeit
meldete mir Herr Dr. Romershausen zu Acken an der Elbe, dass er jene Vor-
sthlaege weiter verfolge, und bald darauf erfand er die nach ihm benannte Luft-
5. “Dr. Romershausen’s Luftpresse, eine in den Koeniglich-Preussischen
Staaten patentirte Maschine zum Extrahiren, Filtriren, und Destilliren. 18
Heft, die Beschreibung und allgemeine Anleitung zum Gebrauch dieser Vor-
richtung nebst einigen Andeutungen zur vortheilhaften Anwendung derselben
in der Haushaltung enthaltend.” Zerbst., bei A. Fuechsel. 1818. Unfortunately
a copy of this pamphlet has not yet been located. However, references to it may
be found in the following journals :—
Buchners Repert. f. d. Pharmacie 6 (1819), p. 317.
Berl. Jahrb. f. d. Pharm. 20 (1819), p. 396.
Buchner’s Anleitung in die Pharmacie, 2ten Aufl., p. 252.
Ann. d. Physik 77 (1824), p. 204.
6. Dinglers Polyt. Journ. § (1821), p. 402.
7. Neues Journ. d. Pharm. 2 (St. 2), (1818), p. 539.
8. Repert. d. Pharm. 4 (1818), p. 406. This originally appeared in the
Literatur-Zeitung for 1818, No. 28.
9. Berl. Jahrb. f. d. Pharm. 20 (1819), p. 392.
10. Repert. d. Pharm. 6 (1819), p. 316.
11. Neues Journ. d. Pharm. 3, 1 (1819), p. 453.
. Schweigger’s Journ. f. Chem. u. Phys. 34 (1822), p. 106.
. Ann. der Physik 75 (1823), p. 423.
. Ibid. 77 (1824), p. 201.
. Mag. f. d. Pharm. 9 (1825), p. 176.
. Dingler Polyt. Journ. 4 (1821), p. 420.
)
2
<i
UT AEN
as
e
e
h
d
n
{ Am. Jour. Pharm.
Studies in Percolaiion July, 1933
3. The Contributions of the Boullays, pére et fils
As pointed out in the introductory remarks, it is not quite true
that the process of percolation “never became popular in France,”
as it is erroneous to claim that it “was ignored in Germany.” That
it was not ignored in Germany has been fully demonstrated in the
previous chapters. The justification for the erroneous statement
may be found in the fact that percolation, as we think of it in this
country, was not practiced in Germany for a long time after we had
adopted and developed it. Its development in this country, however,
is not based on the pressure percolation idea so enthusiastically
pursued for a brief period in Germany, but on the non-pressure
percolation practice developed by the Boullays, pére et fils. It was
through their experimentation and the reports of their experimental
results that the attention of the American pharmacist was drawn to
this process. To anyone at all acquainted with American pharma-
ceutical literature of that period this is not surprising. So far as
there was any American pharmaceutical literature during the first
half of the nineteenth century, this was based largely on English
literature. Next came French pharmaceutical literature. One has
but to page the earlier volumes of the American Journal of Pharmacy
to appreciate the general accuracy of this statement. It was not until
Maisch became editor of the journal that German literature received
due recognition. By this time, however, the German apothecaries
had dropped pressure percolation and had returned to the older
processes of maceration and expression.
To the American student, the work of the Boullays is of two-
fold interest. Firstly, it was they who demonstrated the uselessness
of pressure, no matter what the mode of application, and thus re-
nioved the unnecessary difficulties that accompanied the operation
of Réal’s process and its modification by Romershausen. Secondly,
it was through the reports of the Frenchmen that they became inter-
ested in the process even if they may have known vaguely of the
earlier apparatus and their uses and difficulties. Of this, however,
there appears to be no evidence thus far.
The communications of the Boullays are recorded in three
papers. The first of these appeared in 1833 and was read before
the Société de Pharmacie." In this paper they gave due credit to
earlier workers, including Réal. They pointed out, however, the
disadvantages of the long column of mercury in the Réal press and
346
os ee Studies in Percolation 347
the difficulty of producing tight joints due to the pressure, which to
their minds was unnecessary. In this paper they introduced the
phrase, procédé par déplacement.
Later in the same year they published their second report in
which they gave a very comprehensive treatment of their so-called
méthode de déplacement.*, Once more they emphasized that the high
column of water proposed by Réal had no other effect than to render
the apparatus less applicable and that the Réal apparatus minus the
pressure was nothing more than the cafetiére de Dubelloy, known
for a long time.
The last of these reports was published in 1835.2 This in-
cluded experimental results on new drugs and, the results of several
contemporary workers, among them Buchner, DuBlanc, Soubeiran
and others. For the first time several types of percolators were
described.
Fig. 1—Percolators described by the Boullays.
AB and C D are removable perforated plates.
Fig. 2—Donovan’s apparatus for filtering out of contact with air.
Fig. 3—A small apparatus for hot extraction (cafetiére).
Fig. 2
ENS
=.
j
348 Studies in Percolation —
That these papers stirred up much discussion and interest is
evidenced by the publications in the French and German journals
of the day. While one of their countrymen, Simonin, lauded their
work in the following manner: “Je ne puis terminer sans rendre
hommage a4 MM. Boullay. Leur procéde si simple est applicable
a tant d’operations, qu’il doit produire une veritable révolution en
pharmacie ;’ * Geiger, in Germany, stated in a comment following
an abstract of their first paper in the Annalen der Pharmacie—“Was
hier ueber die Wirkung der Realschen Presse geaeussert wurde, ist
in Deutschland laengst bekannt, und ich habe mich schon vor 17
Jahren in den Schriften: ‘Beschreibung der Realschen Aufloesungs-
Presse u. s. w. Heidelberg 1817,’ so wie in meinem Handbuche der
Pharmacie, dahin ausgesprochen, dass sie ein vollkommenes
Auswaschen (Erschoepfen) der Faser mit der geringsten Menge
Extractionsfluessigkeit sey. Dass uebrigens die Realsche Presse
unnuetz sey und ein Trichter dieselbe ersetzen koenne, glaube ich
nicht.”
Much argument as to priority also arose at this time. Robiquet,
a contemporary of the Boullays, stated at a meeting of the Pharma-
ceutical Society of Paris that a similar apparatus had been used at
the Paris School of Pharmacy “for a long time.” ®
A year later this same investigator described an apparatus’ to
which he had previously referred * and which he had successfully
employed in the extraction of bitter almonds.
Fig. 4—Robiquet’s Apparatus.
ex
ent
rec
the
on
hay
res
effi
in
wit
and
A
O
n
le
r
tl
hi
at
P;
Be
CO
po
th
Pe
co
eff
ce
=
/
| J
\
| / |
Am. Jour as} Studies in Percolation 349
The Boullays answered ® Robiquet’s charges and refuted in no
uncertain terms his false accusations. They made it clear that their
only claims were the application of a new method to a very large
number of medicinal substances which are otherwise altered more or
less by prolonged evaporation.
A further reply by Robiquet *° stated that the Boullays had no
reason to claim priority for the invention, inasmuch as he had used
the same process for a number of years in his private laboratory, in
his factory, and at the Paris School of Pharmacy. He also stated
at this time that he had his apparatus made for him in accordance
with his own specifications by M. Alcoque and that many pharmacists
had asked for it under the name of “the apparatus of Robiquet.”
Guibourt, another contemporary Frenchman, gave credit to
Payen for having developed the process prior to the work of the
Boullays. He expressed himself in the following manner *—
“Secondement j’ai a me réprocher de n’avoir pas cité M. Payen
comme Il’un des premiers qui aient montré l’application que l’on
pouvait faire de la méthode de déplacement a la pharmacie.”
Guilliermond, however, gave due credit to the Boullays for
their work. In a thesis presented to the Ecole de Pharmacie de
Paris, in 1835, in which he carefully traced the development of per-
colation, he stated, after crediting the earlier workers for their
efforts, “Mais il appertenait a MM. Boullay pere et fils de faire de
ce procédé une application plus étendue, soit en étudiant le phénomeéne
d’une maniére générale dans la théorie, soit en donnant de nombreux
exemples de son application aux préparations pharmaceutiques, soit
enfin en provoquant et en appelant sur ce point l’attention et les
recherches des pharmaciens observateurs.” **
The work of the Boullays soon began to attract attention in
the United States and Duhamel, who was the first American to write
on percolation, stated “But to Messrs. Boullay belongs the honor of
having established what was before a mere hypothesis. By their
researches they not only proved that it admitted of very extensive
application, but by furnishing practical results in some new and
efficient preparations they demonstrated it to be of the highest utility
in pharmacy.” **
There is no doubt then that the Boullays should be credited
with their contribution to the evolution of pharmaceutical percolators
and as evidence that their work was not soon forgotten, numerous
350 Studies in Percolation ae -
French references to this appear in the journals as late as the sixties
when the much discussed question before the Committee of Revision
of the United States Pharmacopceia was whether to make maceration
or percolation the official process for the preparation of tinctures and
fiuidextracts.**
REFERENCES
. Jour. de Pharm. 25 (1833), p. 281.
. Ibid. 25 (1833), p. 393.
. Ibid. 27 (1835), p. I.
. Ibid. 26 (1834), p. 100.
. Annalen der Pharm. 7 (1833), p. 318.
. Jour. de Pharm. 25 (1833), p. 322.
. Ibid. 26 (1834), p.-79.
. Robiquet and Boutron had published two papers in 1830 and 1831 describ-
ing in each case the use of a percolator in the extraction of bitter almonds and
mustard seeds. Annales de Chim. et Phys. 44 (1830), p. 352; and Jour. de
Pharm. 23 (1831), p. 279.
9. Jour. de Pharm. 27 (1835), p. 188.
10. Ibid. 27 (1835), p. 113.
11. Jour. de Chim. Méd. 1 (ser. 2), (1835), p. 225.
12. Jour. de Pharm. 27 (1835), p. 349 (abstract by Cap).
13. Am. Jour. Pharm. 10 (1838), p. I.
14. Jour. de Pharm. 74 (1862), pp. 60, 116, 257, 264. Ibid. 75 (1862), p.
4. Early Developments in the United States
It has already been pointed out that interest in the new process
by American pharmacists was aroused by the publications of the
Boullays which became known in this country. So enthusiastic the
pharmacists of the United States became that in their enthusiasm
they were inclined to overlook what had been going on in European
countries and was still going on. As a result they regarded the
process as a typically American development, though its invention
was ascribed to a Frenchman. How even modern writers on the
subject have overlooked the shortlived but enthusiastic development
of pressure percolation in Germany has been indicated. This was
due, no doubt, to the fact that publications in German journals were
unknown to American writers. It remains to be pointed out that
they appear to have been equally unaware of the early pharmaceutical
progress made in English speaking countries. Thus the editor of
the American Druggist and Pharmaceutical Record in 1897+ claimed
that it was the U. S. Pharmacopeeia of 1840 (which did not appear
until 1842) which first made the process official. To this the editor
of the Chemist and Druggist* replies by pointing out that the Edin-
196.
Am. Jour. Pharm. i
july, 1933 Studies in Percolation 351
burgh Pharmacopeceia of 1839 not only made the process official but
enumerated a long list of tinctures, etc., which could be made ad-
vantageously in accordance therewith. He also points out that the
process was being used extensively in England at that time.
If, as Americans, we should be ever ready to give credit to our
German and British confreres, we need not hesitate to point with
satisfaction to the improvements made by our fellow pharmacists
in connection with a process which, according to Tschirch, is the
only improvement made in extraction during the past century.®
The first communication on the subject which appears to have
appeared in an American publication* is a reprint by Soubeiran
which had been contributed originally to a French journal * in 1836.
In it the author reviews the work done by the Boullays, Robiquet,
Guillermond and others, stating that the most important information
is to be found in the publications of Guillermond ° and that the best
apparatus have been described by the Boullays.*. Two years later
the first article from the pen of an American pharmacist appeared.
It is that of the Philadelphia pharmacist Duhamel.* Tracing the
history of the process back to Réal and stressing the contributions
made by the Boullays, he records the results of some of his own
experiments.® A second paper by Duhamel and Procter *° appeared
a year later.‘ They state that while “in France this method has
been extensively applied, in this country it is hardly known, much
less applied.” The process had been made official in the French
Codex of 1835. They make a plea for its introduction into the next
Pharmacopeeia. This step was taken, but with the following pre-
cautionary advice by the medical revisers of the U. S. P.: “And it
is strongly recommended to those who have not made themselves
practically familiar with the various sources of error in the method
of displacement, to postpone its application whenever an alternative
is given in this work until they have acquired the requisite skill.”
With the introduction of fluidextracts into the U. S. P. of
1850, to be made by the process of percolation, a special impetus was
given to the study of this process and of improvements thereon.
Thus Grahame ** concludes an article in which he reviews the history
of the process, the theoretical aspects underlying it, also his own
experiences therewith, with the following words: “ . the great
advantages of the displacement process, as thus conducted, consist
in the facility it affords of obtaining very concentrated solutions of
vegetable substances in a comparatively short period of time.”**
S
1
d
D.
le
e
nN
n
e
n
e
1t
1S
it
al
yf
ir
Pharm.
352 Studies in Percolation aly, 1933
In the same year Squibb* published his first article on the
subject in which he describes and illustrates two types of percolators,
viz., his automatic percolator and his well-tube percolator.** When,
after the Civil War, alcohol became high priced because of an internal
revenue tax of many times the cost of production, he developed the
process of repercolation.*’ Squibb’s work on the subject has been
so extensive and important that it will be considered in a chapter by
itself.
This brief chapter on the early development of percolation in
the United States would be incomplete without reference to the work
of such men as Diehl and Lloyd. Possibly that of Rother, Oldberg
and others should also be mentioned. In closing this aspect of our
subject it may be proper to point out once more how ingrained the
idea had become that percolation was essentially an American process.
For this purpose a paragraph from a paper by Lloyd in 1879 may
be quoted: “Virtually percolation had been employed for ages with
civilized and even partly barbarous nations, as for example, in the
making of saltpetre and potash. Yet while the idea was not new,
its application to the preparation of tinctures and fluidextracts was
original, as far as I can learn, and thus we are indebted to Professor
Procter as though the principle for separating soluble from insoluble
matters was new in the world’s history.” **
REFERENCES
1. Vol. 30, pp. 164 and 283.
2. Vol. 50 (1897), p. 922.
3. Fédération Internationale Pharmaceutique, Lausanne, 1925. Translated
and printed by the Pharm. Journ., vol. 115, p. 362; copied by the Am. Dr. & Ph.
Rec. 73, Dec. 1925, p. 19.
4. Am. Journ. Pharm. 8 (1836), p. 221.
5. Bull. Gén. de Thérap. 9 (1836), p. 349.
6. Thesis presented to the Ecole de Pharm. de Paris; abstract by Cap in
Journ. de Pharm. 27 (1835), p. 349.
7. Journ. de Pharm. 27 (1835), p. 1.
8. For a biographical sketch, see J. W. England, “First Century of the P.
C.
9. Am. Journ. Pharm. to (1838), p. I.
10. Ibid. 11 (1839), p. 180.
11. For a biographical sketch, see J. W. England, /. c., p. 124.
12. U. S. P. 1840, p. XXII.
13. For a biographical sketch, see J. W. England, /. c., p. 115.
14. Proc. A. Ph. A.7 (1858), p. 204.
15. For a biographical sketch, see J. W. England, /. c., p. 216.
16. Am. Journ. Pharm. 30 (1858), p. 97.
17. Proc. A. Ph. A. 15 (1867), p. 391.
18. Ibid. 27 (1879), p. 601.
\
P
Am. Jour. Pharm.
july,1933 ¢ Hundred and Eleventh Commencement 353
THE ONE HUNDRED AND ELEVENTH ANNUAL
COMMENCEMENT OF THE PHILADELPHIA
COLLEGE OF PHARMACY AND SCIENCE
HE One Hundred and Eleventh Annual Commencement was held
in the College Auditorium at 8 P. M., June 7, in the presence
of a large audience.
The invocation was pronounced by the Reverend Father Joseph
A. McDonald, rector of the Church of Our Mother of Sorrows. The
candidates for graduation were presented to President Wilmer
Krusen by Dean of Pharmacy, Charles H. LaWall and by Dean of
Science, Julius W. Sturmer. Degrees in course in pharmacy, chem-
istry, bacteriology and pharmacognosy were conferred upon 161
students.
In addition, the degrees of master in pharmacy honoris causa
were received by the following:
Dr. Theodore J. Bradley, distinguished pharmacist, chemist and
educator, who has served twenty-one years as dean of the Massachu-
setts College of Pharmacy in Boston.
Henry K. Muiford, 1887, graduate of this College, founder and
long the directing head of the H. K. Mulford Company, pioneer
producers of vaccines and serums and now director of the biological
Theodore J. Bradley Henry K. Mulford Jacob L. Nebinger
\
\
354 One Hundred and Eleventh Commencement { A™- jour. harm.
and research laboratories of the National Drug Company, and presi-
dent of the Mulford Colloid Laboratories.
Jacob L. Nebinger, 1885, graduate of this College, for twenty-
four years in charge of the prescription department of the Philadel-
phia drug store founded by the late William H. Llewellyn, 1877, and
now a member of the teaching staff of the College.
An orchestra composed of West Philadelphia high school stu-
dents, under the direction of Harry P. Hoffmeister, assistant pro-
fessor of German at the College, presented a musical program during
the ceremonies.
The address to the graduates was delivered by Dr. George Earle
Raiguel, physician, author and traveler, following which President
Krusen gave a farewell message to the graduating classes. Degrees
in course, certificates and prizes were awarded as follows:
MAsTER IN PHARMACY (Honoris Causa)
Theodore J. Bradley Henry K. Mulford
Jacob L. Nebinger
Docror IN PHARMACY
Herbert Bohn
MASTER OF SCIENCE IN CHEMISTRY
Joseph C. Haefelin Allen F. Peters
Amelia M. de Ponce
MASTER OF SCIENCE IN PHARMACY
Kurt E. Steiger
MASTER OF SCIENCE IN BACTERIOLOGY
Jeanne D. Dreier John N. McDonnell
BACHELOR OF SCIENCE IN CHEMISTRY
Albert Bloom Richard E. Houghton
Stephen F. Colalongo Edward A. Listokin
Lane V. Collins, Jr. Wilbur B. Millington
Walter L. Nelson
BACHELOR OF SCIENCE IN BACTERIOLOGY
Joseph H. Kelly Werner W. W. Ruthenberg
BACHELOR OF SCIENCE IN PHARMACY
Elizabeth C. Adams James Q. Mackey
Harrison R. Boggs Saul Malasky
William L. Byrnes Abraham Marcus
Abraham Cohen Sigmund Moerman
Rubin Greenberg Louise A. Moffses
Francis P. Kelly, Jr. Margaret A. Morgenthaler
Guido Lorenzoni Mary B. O’Connor
George A. Panarc'!lo
Estelle A. Pavilonis
Samuel A. Rosenbaum
at One Hundred and Eleventh Commencement
Joseph R. Santoro
Michael M. Selector
Linwood F. Tice
PHARMACEUTICAL CHEMIST
Albert J. Feicht, Jr.
Bernard Protigal
GRADUATE IN PHARMACY
Llewellyn S. Adelman
Frances R. Allone
Esther N. Altshuler
William F. Andiario
Edward N. Arshan
Edgar C. Bekes
Wallace S. Bell
Charles W. Bennett, Jr.
Julius Bernstein
Richard L. Boaman
Harry H. Bock
Joseph M. Boltz
Martin R. Bower, Jr.
Adelaide H. Brandt
William J. Braude
Francis J. Brocani
Milton J. Brown
John M. J. Burns
Mary Cammarota
Edward R. Carl
Vincent C. Cartusciello
Nathan Cohen
Carmelo J. Coletta
John A. Dereskevich
August Di Riego
William G. Dreibelbis
Miriam C. Dubin
Eugene C. Dunham
Charles Eckstein
David N. Ellis
Frederick Else, Jr.
Frank C. Falchek
Harry J. Feather
Natalie R. Feldman
William Ginzburg
Cecil J. P. Gray
Frank A. Groblewski, Jr.
Woodrow W. Groff
Harold M. Gruber
Jerome F. Haaz
Harold R. Hafer
Orville Hann
Edmund V. Havira
Richard H. Herbine
Samuel Herman
Elmer C. Hillman
William M. Holsberg
Herman G. Hornung
Solomon Isserman
Michael Javoronok
George D. Jenkins
Hiram E. Keefer
Joseph P. Kelly
Martin Kirshenbaum
Bernard B. Kline
Ralph L. Kline ~
Isryl M. Krause
Walter J. Kropp
Robert H. Lentz
Harry A. Levenson
Harry H. Levin
Louis S. Lyon
Claude E. Markley
Charles R. Mattei
Anthony J. Mazzucca
Ralph D. McKinstry
Russell A. Miller
Nathan Mirman
Emanuel H. Modeck
William L. Morrison
Joseph Ness
William E. Ogden
Edward Oxman
Benjamin Parson
Ray T. Peffer
Maxwell S. Perlstein
Margaret M. Petruno
Charles R. Pimlott
Claude P. Pinkerton
Edmund M. Points
Fred P. Ragains
Harry W. Rementer, Jr.
355
One Hundred and Eleventh Commencement A™- Jour.
Robert M. Reynolds
Herman J. Rocconi
Sidney D. Rosenfeld
Isadore Rosenthal
Cyril A. Sakalosky
Reynold L. Salvatore
William L. Scharadin
Arthur Scott
David P. Secon
David M. Sherrick, Jr.
Thomas D. Simmons
Edward J. Smith
Narcey A. Stapinski
Donald B. Stegner
John J. Stepanik
Marlin B. Stetler
William W. Stinson
John R. Stout
Samuel F. Tancredi
Howard F. Watson
Albert J. Windfelder
Joseph A. Yantoshik
Jacob Zalesky
Walter J. Zukoski
CANDIDATES WHO HAVE COMPLETED SPECIAL COURSES AND
HAVE QUALIFIED FOR CERTIFICATES
(This does not include students who completed courses in these subjects
for credits for a degree.)
CERTIFICATES IN BACTERIOLOGY
Seymour Halbert
Thomas W. D. Harrison
Lory C. McAllister
CERTIFICATES IN CLINICAL
Harry J. Bailen
Cecil J. P. Gray
Seymour Halbert
Thomas W. D. Harrison
Lory C. McAllister
Joseph A. Montalbano
Joseph M. Muniz
Marie A. Reilly
CHEMISTRY
George A. Miller
Joseph M. Muniz
Marie Anne Reilly
Sol Sherson
Genevieve D. Slaughter
Award of Prizes 1933
GRADUATES IN PHARMACY
Designated as “Distinguished”
With General Average Over 90%
Frank A. Groblewski, Jr.
Walter J. Kropp
Margaret M. Petruno
Robert M. Reynolds
Marlin B. Stetler
Designated as “Meritorious”
With General Average Between 87% and 90%
Edward N. Arshan
Edgar C. Bekes
William J. Braude
Francis J. Brocani
Eugene C. Dunham
Elmer C. Hillman
Michael Javoronok
Robert H. Lentz
Isadore Rosenthal
David M. Sherrick, Jr.
The Procter Prize, for the highest average of the class, awarded to:
MarGaret M. Petruno
|
I
h
Sol Sherson fe
ai
M
PI
be:
aw
be
a One Hundred and Eleventh Commencement 357
The Wit1am B. Wess MemortiAL Prize, for the highest general average
in the branches of Operative Pharmacy, Analytical Chemistry and Pharmacog-
nosy, awarded to:
Maruin B. STETLER
Honorable Mention to
Llewellyn S. Adelman Harold M. Gruber
Richard L. Boaman Walter J. Kropp
Eugene C. Dunham Margaret M. Petruno
Robert M. Reynolds
The Frank Gress Ryan Prize, endowed by the Class of 1884, as a
memorial to their distinguished classmate, for the best average in the Chemical
and Pharmaceutical Laboratory Courses, awarded to:
B. STETLER
Honorable Mention to
Eugene C. Dunham Robert H. Lentz
Harold M. Gruber Margaret M. Petruno
Walter J. Kropp Robert M. Reynolds
The Matscu Borany Prize, offered by Sinclair S. Jacobs of the Class of
1909 to the member of the graduating class who shall have presented the best
herbarium collection of plants, or the best thesis on the microscopical structure
of medicinal plants, awarded to:
SauL MALASKY
The RemMINGTON MemorrAL Prize, offered by the Estate of Joseph P.
Remington, for the highest average in the examinations of Operative Pharmacy
and Dispensing, awarded to:
Marin B. STETLER
Honorable Mention to
Llewellyn S. Adelman Louise A. Moffses
Harold M. Gruber Robert M. Reynolds
Harold R. Hafer Joseph R. Santoro
The Manton N. KLiNne THEORETICAL PHARMACY PRIZE, offered by the
Mahlon N. Kline Estate, for the highest average in Theory and Practice of
Pharmacy, awarded to:
WALTER J. Kropp
Honorable Mention to
Margaret M. Petruno Marlin B. Stetler
The Lamspa Kappa S1cMA Prize, a Sorority Key, to the sorority mem-
ber in the Ph. G. Class attaining the highest average during the Senior year,
awarded to:
Marcaret M. PEetruNO
And the Sorority Key to the member making the highest average in the
Senior year of the 4-year Courses, awarded to:
ELiIzABETH C, ADAMS
358 One Hundred and Eleventh Commencement
Gold Medals awarded by the Alumni Association to the student of the
Ph. G. Class and to the student of the 4-year courses who attain the highest
scholastic averages, are awarded to:
Margaret M. Petruno Saul Malasky
Winpvow Display Prizes awarded by Sharp and Dohme:
First Prize, to
Harry A. Levenson Claude E. Markley
Louis S. Lyon Emanuel H. Modeck
Second Prize, to
Walter J. Kropp Robert H. Lentz
Harry H. Levin
Third Prize, to
Cyril A. Sakalosky David P. Secon
Arthur Scott David M. Sherrick, Jr.
Honorable Mention to
Cecil J. P. Gray Fred P. Ragains
Francis P. Kelly, Jr. Robert M. Reynolds
Estelle G. Pavilonis Michael M. Selector
IoDINE FOR GoITER May Propuce AcNE—A skin eruption re-
sembling the acne of adolescence may follow the use of iodine for
goiter prevention, it appears from a note by Dr. Karl G. Zwick of
Cincinnati to Science.
This iodide acne does not occur in everyone, but does occur in
persons who already have an idiosyncrasy to iodine when they start
taking it as a goiter preventive, or in persons who develop sensitive-
ness to it.
Iodide acne seems to occur more often since the drinking water
of cities is chlorinated, Dr. Zwick has observed. This is not surpris-
ing, he explains since all the halogens, the chemical group to which
iodine and chlorine belong, are irritating to the glands of the skin.—
Science News.
ers
dir
picl
the
hon
he
him
hun
ried
So
phy
min
was
anal
of t
a co
A
ha
po
to:
ist
kit
fat
in
sta
poi
dye
str
the
Am. «<= pone | Medical and Pharmaceutical Notes
MEDICAL AND PHARMACEUTICAL
NOTES
FataL WitH Soprum NitritE—Sodium nitrite is
handled by many textile supply firms, and is distributed without
poison labels to cotton mills and dye plants. We have in our labora-
tory stock room containers from three different manufacturing chem-
ists bearing sodium nitrite labels, but without a poison mark of any
kind.
Search of the chemical literature reveals no reported case of
fatal poisoning with sodium nitrite in the United States. Two deaths
in Bavaria, and four in Algeria, were attributed to sodium nitrite.
Sodium nitrite is not included in the long list of poisonous sub-
stances that the North Carolina Code specifies must be sold under
poison label. Since this substance is used in large quantities in the
dye rooms of many mills, we consider it wise to place on record a
striking case of fatal poisoning that has occurred in North Carolina.
On October 28, 1932, we were called to investigate the death of
the two-year-old son of L. D. Ray, a worker in a cotton mill in Hunt-
ersville, Mecklenburg County, N. C.
When we arrived on the scene, the child was dead. His brother
directed us to the junk pile near the mill, and stated that the child
picked up a small quantity of a white substance, which we saw on
the junk pile, put it in his mouth, and at once ran crying toward his
home, which was about 300 feet distant. Before he reached there,
he fell to the ground vomiting. Members of his family hurried to
him, and found him pale and weak. On picking him up his limbs
hung limp, he was desperately weak, and still vomiting. He was car-
ried directly to his home and the mill physician summoned at once.
So rapid was the action of the poison that the child died before the
physician arrived. His mother stated that not more than fifteen
minutes had elapsed since she had picked him up.
With the aid of the physician, a portion of the stomach contents
was removed. The white substance obtained from the junk pile on
analysis in the laboratory proved to be sodium nitrite. Examination
of the stomach contents showed that they were alkaline and contained
a considerable quantitiy of sodium nitrite. The solid particles of the
360 Medical and Pharmaceutical Notes pharm.
stomach contents showed a distinct chocolate brown color. Stomach
contents are normally acid, but the hydrolysis of a substance like
sodium nitrite would cause the alkalinity. This confirms the detec-
tion of a large amount of sodium nitrite in the stomach.
To verify our opinion that sodium nitrite is a violent poison,
and was the cause of this child’s death, we administered 65 milligrams
(1 grain) in a capsule to a cat weighing 2.6 pounds. In five min-
utes the cat began violent vomiting. Four minutes later it lost con-
trol of muscles, sprawled on the floor, and began screaming. The
screaming slowly died down and in six minutes more, fifteen minutes
after the dose was given, the cat was dead. This certainly shows
the extremely poisonous nature of sodium nitrite.
Chemical literature records the two following cases of fatal
nitrite poisoning :
H. Molitoris reports two cases of fatal sodium nitrite poisoning
occurring within a few months in the same factory, one on October
4, I910, and one on April 13, 1911. These were workmen in a fac-
tory where sodium nitrite was manufactured in Innsbruck, Austria.
L. Musso in 1925 reports four cases of death from sodium ni-
trite poisoning in a drug store in Algeria, by taking sodium nitrite
from a bottle labeled “Sodium Tartrate.”
The facts presented in this paper show that the use of sodium
nitrite as a meat-curing agent might be attended with great danger.
—H. B. Arbuckle and O. J. Thies, Jr., Davidson College, Davidson,
BIBLIOGRAPHY
‘ Czaplewski, Vierteljahrsschr. gericht. Med., [3] 43, 356.
Hesse, Erich, Arch. exptl. Path. Pharmakol., 126, 209-21 (1927).
Heubner, W., and Meier, Rolf, Nachr. Ges. Wiss. Gottingen. Math. physik.
Klasse, 1925, 73-7. ;
LaFranca, S., Arch. fisiol., 8, 14-16; Zentr. Biochem. Biophys., 12, 524.
Mladoveanu, M. C., Compt. rend. soc. biol., 99, 606-10 (1928).
Molitoris, H., Vierteljahrsschr. gericht. Med. [3] 43, 2nd Suppl., 280-97
(1912).
Musso, L., J. pharm. chim., [8] 4, 345-60 (1926).
Walsh, T. C., Food Manuf., 7, 49-51 (1932).
—Ind. and Eng. Chem. N. E. July, 1933, p. 202.
Nine Kinps oF WatEer—Water is the most common, and one
of the most important materials of the earth’s surface. It is the prin-
C
t
t
t
(
t
V
a
r
u
CC
d
tl
T
Am. Jour. oust™-} Medical and Pharmaceutical Notes 361
cipal ingredient of our bodies and of most of our foods. Chemists
find it their most useful solvent, and nature has used it most abun-
dantly in modifying the earth we live on. What more natural than
that the properties of water be used to define most of our standards,
such as weight, density, viscosity and temperature? We live by
water. Why not measure by it?
Until a very few years ago, no reason could be assigned for
questioning the unique status of water as a material of dependable
properties. Thanks to recent discoveries in science, such questioning
must be done in all seriousness. In the formula of water (H2O)
each atom of hydrogen was found to have 1.008 units of weight and
each atom of oxygen, 16.000 parts (by definition). Therefore, a
molecule of water (at least in the condition of steam) should have
a weight of 18.016 units. Wherever found, if sufficiently purified,
water at the temperature of its greatest density was of specific gravity
1.000, froze at o degrees Centigrade and boiled at 100 degrees Cen-
tigrade, by definition.
Now, we know that there are two kinds of hydrogen, exactly
alike in every chemical way, but the second, or newly-found “isotopic”
form, is twice as heavy as the older, well-known form. Chemical
compounds containing it are of course heavier by the difference in
the weight of the hydrogen atoms present, so that water based on
this new hydrogen should be heavier than normal. To make the mat-
ter more complex, oxygen has been found to exist as three isotopes.
Ordinary oxygen is predominantly 16-unit oxygen, but contains
some 17-unit and some 18-unit atoms. Water made from the heavier
hydrogen and the heaviest oxygen should be materially heavier than
that made from the lightest atoms. Intermediate forms of water
would, in their pure form, contain in each molecule one of the heavy
and one of the light isotopes of hydrogen, together with an isotope
of oxygen.
Prof. G. N. Lewis, of the University of California, has very
recently succeeded in concentrating the heavy form until his best
sample has a specific gravity of 1.035. While this probably contains
under 35 per cent. of the heaviest water, there is a great enough
concentration of the new heavy water to show vividly the density
difference as well as a slightly lessened refractive index. Further,
the freezing and boiling points are above those of common water.
The first part of the concentration of water composed of the heavier
362 Medical and Pharmaceutical Notes
hydrogen and oxygen atoms consists in electrolyzing large amounts
of water, whereby the lighter waters are decomposed more easily
than the heavier forms. While this newer water differs in all physical
ways from the old, it is not to be expected that it will behave de-
tectably different in any chemical reaction. Water is still water, but
we must now specify which individual or mixture of nine possible
different waters is meant when defining the basis of our standards
of density, temperature, and certain other physical properties. Again
science has revealed the stupendous complexity of simple things.—
Industr. Bull., A. D. Little.
SoptumM MorrHuATE. VARIATION IN COMMERCIAL SAMPLES.
R. T. M. Harnrs—An examination of five commercial samples of
“sodium morrhuate 10 per cent.” showed that the term is very dif-
ferently interpreted, and that a standard is needed. It will be seen
from the iodine values that only in sample C has an attempt been
made (almost completely successful in this case) to free the drug
from sodium oleate; B and D are partly purified, and A and E con-
tain all the original oleic acid from the cod-liver oil. The determina-
tion of the iodine value of the fatty acids is important, since sodium
oleate is very possibly both more toxic and less active as a sterilising
agent than are the sodium salts of the more highly unsaturated fatty
acids. In the subjoined table the colour values are those obtained
with Lovibond’s tintometer (1 cm. cell).
4
Sample. A B C D E
Semi-solid, Liquid, Liquid, Liquid, Gelled,
curdy clear clear turbid _ turbid
Appearance yellow yellow orange yellow orange
Colour, yellow units 11.8 18.0 16.0 9.2 59.6
Colour, red units 2.2 2.2 2.4 0.4 15.6
Colour, general absorption 5.4 re) 0.6 4.8 13.2
Total 19.4 20.2 19.0 14.4 88.4
Fatty acid content, per cent. 9.45 9.03 9.74 7.0 8.15
Iodine value, found 178.5 183.9 241.2 193.5 169.5
Phenol Phenol Tricresol Phenol Phenol
per cent. percent. percent. percent. per cent.
Preservative in fatty acid after
isolation 3.4 3.5 2.6 4.9 3.8
Iodine value, corrected 159.3 164.1 226.5 165.8 148.0
—Lancet, 1933, 224, 748-749, through The Analyst.
Am. ~Medical and Pharmaceutical Notes 363
“Spor” Tests ror SoME Orcanic Compounps—A number of
macro-scale reactions of aromatic amines and aldehydes are adapted
for use as “spot” tests. Aniline (i).—A drop of a solution of ani-
line salts on a filter paper moistened with saturated calcium chloride
solution gives a blue-violet colour, turning red-brown, and finally dis-
appearing. The smallest amount detectable is 1y of aniline sulphate.
If, after the blue colour has faded, the paper is held over ammonium
sulphide a rose-red colour appears; 0.25y of aniline sulphate can be
detected. Benzidine, under the same conditions, gives a blue fleck;
0.02y can be detected. Sulphanilic acid gives no colour until the paper
is held over ammonium sulphide vapour, when a red coloration ap-
pears; 0.7y can be detected. (ii) When a drop of an aniline salt
solution, a drop of calcium chloride solution, and a drop of aqueous
phenol are superimposed on a piece of filter paper, and the paper is
held over ammonia, the edge of the drop is flecked with blue. The
reaction is sensitive to 0.75y of aniline sulphate. Sulphanilic acid
gives the same reaction, benzidine does not.
Sulphanilic. Acid—(i) A piece of filter paper is moistened with
sulphanilic acid solution, with an a-naphthylamine solution in acetic
acid, and then with sodium nitrite solution. A yellow-brown red-
edged fleck is formed ; the test is sensitive to 0.1y and aniline does not
interfere. (ii) A drop of sulphanilic acid is treated with nitrous
oxide and then with a-naphtholate solution; a red fleck is formed,
sensitive to 0.02y. Aniline gives a red-brown colour.
Diphenylamine——When a drop of an alcoholic solution of di-
phenylamine is treated on filter paper with a dilute sulphuric acid
solution of potassium dichromate, a blue fleck is formed; the test
is sensitive to O.Iy. In the presence of aniline a dark blue or green
colour appears after a few minutes. Benzidine does not interfere.
Benzidine—(i) An acetic acid solution of benzidine is treated
on filter paper with a drop of potassium dichromate; a dark blue
colour is formed, sensitive to 0.05y. Dilute mineral acids decolorise
the fleck. (ii) A drop of dilute copper sulphate solution, benzidine
in acetic acid, and potassium cyanide solution, give a dark blue fleck
on filter paper, sensitive to 0.1y; aniline does not interfere. (iii) Gold
chloride solution gives with benzidine on filter paper a red-brown,
blue-rimmed fleck; sensitive to 0.0075y. Other amines give similar
colours.
364 Medical and Pharmaceutical Notes { A™- jour. Dharm.
a-Naphthylamine—A drop of the hydrochloride of a-naphthyl-
amine in solution, mixed with solution of potassium dichromate, acid-
ified with sulphuric acid, gives a red-violet or blue fleck; sensitive to
0.3y of a-naphthylamine hydrochloride. B-Napthylamine does not
interfere.
B-Naphthylamine.—Filter paper strips moistened with an alco-
holic solution of B-naphthylamine hydrochloride and acetic acid, and
placed in furfural vapour or in an acetic acid solution of furfural,
give a violet coloration, developing slowly ; sensitive to 0.3y. a-Naph-
thylamine does not interfere, but aniline and~ benzidine give a blue
colour.
Phenylhydrazine—A drop of a saturated solution of ammonium
molybdate, followed by a drop of phenylhydrazine hydrochloride on
a filter paper, and held over ammonia, gives a green-blue colour; sen-
sitive to O.Iy.
Pyridine—A drop of a pyridine solution, followed by a drop
of aniline or aniline water, and a drop of brom-cyanide (concentrated
potassium cyanide solution and bromine), when placed on filter paper,
give a yellow-red colour, sensitive to 0.Iy.
Formaldehyde.—(i) Filter paper moistened with formaldehyde
solution is treated with a fragment of phenylhydrazine hydrochloride
and then with a drop of sodium nitroprusside solution. On adding
concentrated sodium hydroxide solution a blue evanescent colour ap-
pears. In the absence of formaldehyde the reagents give a red-yellow
colour ; the test is sensitive to 0.ry. Acetaldehyde does not interfere.
(ii) A drop of formaldehyde solution on filter paper (free from iron
and copper) is treated with powdered phenylhydrazine hydrochloride
and a drop of 5 per cent. potassium ferricyanide solution and con-
centrated hydrochloric acid. A red-violet fleck is formed; sensitive
to 0.04y. Acetaldehyde does not interfere. (iii) A formaldehyde
solution is placed on filter paper and treated with a drop of phloroglu-
cinol solution, and then with dilute sodium hydroxide solution. A
red-brown fleck is formed; sensitive to 0.03y.
Acetaldehyde—When a drop of acetaldehyde solution, piperi-
dine, and sodium nitroprusside solution are placed on filter paper, a
rim of blue is formed, changing to red with alkali; sensitive to 0.4y.
Formaldehyde does not interfere. Acetone gives a light red colour.
C
r
a
4
R
ac
in
Pp
det
TI
duc
tu
ma
cu
gu
me
hyd
chic
duc
Am. bmi nies | Medical and Pharmaceutical Notes 365
Furfural.—When treated with a solution of aniline in 80 per
cent. acetic acid (1:1) a blue colour is formed ; sensitive to 0.05y. The
reactions with benzidine and a-naphthylamine are not so sensitive.
Vanillin—A drop of alcoholic vanillin solution, when treated
with a drop of phloroglucinol in concentrated hydrochloric acid, gives
an orange fleck, turning red; sensitive to Ily—I. M. Korenman, J.
Chem. Ind, (Russ.), 1931, 8, 508-510; Mikrochem., 1932, 11, 473-
475, through the Analyst.
CHEMICAL-PHARMACEUTICAL INDUSTRY WELL DEVELOPED IN
Russta—One of the few branches of the chemical industry that has
actually exceeded the requirements of the five-year plan is that deal-
ing with pharmaceuticals. This is shown in the following table in
price levels of 1926-27:
Planned Production Actual Production
Million Rubles Million Rubles
1928 44.1 27
1929 48.0 42
1930 50.0 48
1931 66.4 57
1932 60.0 11@
Besides the production of pharmaceuticals, this industry also un-
dertook the manufacture of certain purely chemical preparations.
Through the scientific institute devoted to the drug industry, the pro-
duction of acetylsalicylic acid has been improved, and the manufac-
ture of pyramidone has become feasible. Progress has also been
made during the past few years in the manufacture of silver, mer-
cury, bromo-, iodo-, bismuth, and arsenic preparations, of alkaloids,
guaiacol, and salicyl derivatives, benzoic and lactic acids, and hexa-
methylene tetramine.
As early as 1929-30, alkaloids were produced in the following
amounts per annum: cocaine, 1.22 tons; pantopan, 0.24 ton ; morphine
hydrochloride, 0.63 ton; codeine, 2.88 tons; ethylmorphine hydro-
chloride, 0.44 ton; and diacetylmorphine, 0.12 ton. In 1932, the pro-
duction of iodine and bromine was 80 and 200 tons, respectively.
366 Medical and Pharmaceutical Notes ioe
Attempted cultivation of cinchona species was undertaken in
1931, in the Northern Caucasus. In Leningrad a plant for produc-
ing camphor, with an annual capacity of 400 tons per annum, has
been erected.
Ever since 1882 Russia has extracted santonin from wormseed,
large amounts of which are found in the wide steppes of Turkistan
and furnish the raw material for a factory in Tschimkent. In 1930,
the export of santonin reached 9.4 tons, but in 1931 shrank to 3.6
tons.—News Edition, Jour. Ind. & Eng. Chem., June, 1933, p. 195.
SUMMARY OF CHANGES IN THE Proposep NEw Foop anp
Drucs Act—Drugs considered dangerous to health are deemed adul-
terated.
Secretary of Agriculture may prescribe methods of testing U. S.
FP. or N. F. products when such tests are not given, or may add to
tests when he so desires.
Cosmetics are included in the act and may be deemed adulterated
if considered dangerous to health, or if they contain poisonous or
deleterious substances.
Drugs and cosmetics must bear content statement on label.
Labels of drugs may bear names of diseases for which products
are not specifics, but are merely palliatives, if a statement that the
drug is not a cure is made.
Drug is misbranded if the label contains statement contrary to
general medical opinion.
Drug is misbranded if not packaged or labeled in form and man-
ner prescribed by Secretary of Agriculture for the prevention of
deterioration of those drugs subject to deterioration.
Drug is misbranded if the container is made, formed or filled
to mislead purchasers; if it is an imitation of another drug; if it is
offered for sale under the name of another drug.
Antiseptics and germicides must give on labels for each use the
method and duration of application necessary to kill all micro-organ-
isms in the vegetive or other active form with which it comes in con-
tact when so used; or there must be given on label the specific micro-
organisms which the product affects together with the conditions,
duration of application under which the product kills all such micro-
organisms.
r. Pharm.
, 1933
Am. Jour oa Medical and Pharmaceutical Notes 367
Drug and cosmetic advertising is regulated so that statements
must conform to facts as in the case of label statements.
Drug advertising is further regulated so that no advertising to
other than the medical and pharmacological professions is allowed for
products claimed to have any effect upon any of a long list of dis-
eases written in the bill; and further empowering the Secretary of
Agriculture, as he sees fit, to add to the list of diseases in which
self-medication is dangerous, and prohibiting consumer advertising
of products claimed to affect such diseases.
Permits are required for factories producing those classes of
drugs and cosmetics which Secretary of Agriculture deems may be
injurious to health, when the Secretary feels that such danger can-
not be ascertained after such articles have entered interstate com-
merce.
Inspectors of the department are to inspect drug and cosmetic
factories with the permission of the owners. District courts are
granted power of injunction against shipment of goods from those
factories which do not permit inspection.
Manufacturers may request inspection of their plants at cost,
and then use on labels fact that they have been inspected by Gov-
ernment and found to be in conformity with law.
Secretary of Agriculture will draw up entire regulations for
enforcement of the act with the exception of that relating to imports
in which the Secretary of Treasury shall concur. Regulations for the
present act are drawn up by the three Secretaries of Agriculture,
Commerce and Treasury—The Drug & Cosmetic Industry, June,
1933.
THe CAMpPHoR OF ComMMERCE—There are two chief sources of
the commercial supply of camphor—Japan and Germany—but syn-
thetic camphor is now being made in America by the du Pont Com-
pany. The water-white liquid is ordinarily prepared from what is
commonly called “camphor gum,” which is not a gum but a crystalline
substance. Pharmacists use it; curators know its value; housewives
find it a household necessity; but the greatest amount of camphor
finds its way into the manufacture of industrial products. Camphor
is an indispensable raw material in the pyroxylin plastic industry.
As a plasticizing agent in transforming cellulose into “pyralin” and
)
)
368 Medical and Pharmaceutical Notes ~~“
photographic film, nothing better has been found so far. For cen-
turies practically all the natural camphor used in the United States
was imported from China, Japan, the East Indies, Formosa, and
other eastern lands where the camphor forests are abundant; but
since 1899 practically all the world’s supply of natural camphor has
keen controlled by the Japanese government. For years American
manufacturers had to battle a Japanese monopoly. In 1880 the
Department of Agriculture imported camphor berries and young
trees from Japan and planted them in southern and southwestern
states. These attempts had to be abandoned because of the World
War. Controlled prices after the war brought the question of syn-
thetic camphor sharply into focus. In 1803 an apothecary by the
name of Kindt introduced HCl into oil of turpentine and obtained
a crystalline product resembling camphor, but in reality it was borony]
chloride. Bertholet, a French chemist, is said to have been the first
to produce a chemically made camphor. This was in 1858. Others
made contributions ; but the synthetic product caused little uneasiness
in Japan until late in the first decade of this century when European
competition threatened Oriental monopoly. In 1923, there were im-
ported 3,240,322 pounds of refined camphor at a value of $0.735
per pound as against 488,684 pounds of synthetic valued at $0.619
per pound. In 1932, there were imported 941,459 pounds at $0.353
per pound as against 1,416,331 pounds synthetic camphor valued at
$0.278 per pound. Camphor gathering has been and still is in some
1egions a risky business. The savages in the hinterland of Formosa,
where the trees grow, are head hunters. Today trained operators get
evérything out of the wood that is valuable, and in Japan a reforesta-
tion program insures a future supply of trees. While Germany was
busy breaking down the Japanese monopoly, American chemical con-
cerns were inactive ; but as early as 1900 one American concern started
production at Niagara Falls. Others followed, only to drop by the
wayside. Today, however, synthetic camphor is being manufactured
by a new du Pont process from southern turpentine. Apparently
this is the only attempt in America to manufacture “synthetic” cam-
phor of high quality in quantity to supply our domestic needs.
“Synthetic” is really a misnomer for the product is not built up from
simple elements but starts with a complex organic substance. It is
a strange coincidence that the basic material for this product also
comes from a tree—the southern pine-—Anon. Du Pont Mag., 27,
1-3, 15-16 (Apr., 1933) through Jour. Chem. Educ.
Am. Jour. ta { Medical and Pharmaceutical Notes 369
Soprum AMYTAL IN STRYCHNINE Potsoninc—The modern
treatment of strychnine poisoning consists chiefly and pre-eminently
in the intravenous administration of sodium amytal, either during
the premonitory stage or when the convulsion has begun. The dose
is 744 grains (0.5 gm.). Smaller or larger doses to be used as re-
quired and repeated with each convulsion. In severe cases, when
repeated injections of the barbiturates are required, they may be sup- .
plemented with tribrom-ethanol anesthesia. Giving a chemical anti-
dote, such as tannic acid, and lavage of the stomach are also impor-
tant. Chloral and bromides may also be given.
To date, eleven cases have been reported of human strychnine
poisoning treated successfully with sodium amytal.—Stalberg and
Davidson, Jour. A. M. A., July 8, 1933, p. 104.
Non-SutFipe stannites are used as ac-
tive ingredients in preparing depilatories. Many objectionable fea-
tures of sulfides in depilatories are overcome. New preparations are
non-toxic, non-irritating, effective, rapid in action, stable in air, light
in color (even pure white) and odorless or easily perfumed. Sodium
stannite is highly effective and is used with suitable wetting agents to
aid in penetration of active principle. Pure soap, preferably sodium
oleate, is preferred. Inert fillers, such as natural white clays, white
diatomaceous earth, alkali earth silicates, for example magnesium
silicate, are also used. Fillers act as buffers and reduce any caustic
action of depilatory on skin—Drug & Cosmetic Industry, June, 1933.
{ Am. Jour. Pharm.
Book Review july, 1933
BOOK REVIEW
URINE AND URINALysiIs. By Louis Gershenfeld, Ph. M., B. Sc.,
P. D. Professor of Bacteriology and Hygiene and Director of
the Bacteriological and Clinical Chemistry Laboratories at the
Philadelphia College of Pharmacy and Science. 12mo, 272 pages,
illustrated with 36 engravings. Published, 1933. Limp bind-
ing, $2.75 net, Lea & Febiger, Philadelphia, Pa.
Written by one who has had a large experience in teaching as
well as in performing the work described in the book, this handy
volume should be eminently practical and dependable. Generally
speaking the laboratory manuals on urinalysis have been altogether
too terse and brief—except in those few cases where they err in the
direction of toomuchness.
This work affords the happy medium—compact, complete and
certainly up-to-date. And furthermore it is specific to its subject.
It has been specially written for graduates in pharmacy, chem-
istry, bacteriology and the allied professions; for nurses and techni-
cians and for those general practitioners in medicine whose interest
in this subject centers about the performance of urinalyses.
The author writes from a long experience which has included the
personal performance of over 25,000 urinalyses, and the supervision
of many times that number. He presents the subject in ali its as-
pects, including the laboratory methods of examination, the nature
of cases in which abnormal findings prevail, and the interpretations
of: the examinations suggested. The work is conveniently organized
and an orderly arrangement of the material is maintained throughout.
The up-to-dateness of the work is particularly evident—as, for
instance, in the chapter on nitrogen retention and kidney function
tests.
A number of brand new and original illustrations relieve this
book of the criticism so often made that authors of such books are
too wont to use time-honored and trite cuts borrowed from other
sources, in order to minimize illustration costs.
The printing and binding are well done—and the work is singu-
larly free from typographical and other errors.
Altogether one feels that this is a helpful book, sensibly and
accurately written, not compiled just to please a whim, but rather
to fill a real need. In its particular field there is no book quite its
equal.
Ivor GRIFFITH.
370
x
a
|
‘
Live Music Archive
Librivox Free Audio
Metropolitan Museum
Cleveland Museum of Art
Internet Arcade
Console Living Room
Books to Borrow
Open Library
TV News
Understanding 9/11