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LIBRARY

/ * Of the,'

University' of." California.



Class






INTRODUCTION



TO THE



ANALYSIS OF

DRUGS AND MEDICINES

AN ELEMENTARY HANDBOOK
FOR THE BEGINNER

By BURT E. NELSON

w

Laboratory of the Binghamton State Hospital, and of Nelson and Lauder,

Binghamton, N Y. ; Chemist to the New York State Hospitals,

The Department of Health, Board of Water

Commissioners, etc.



FIRST EDITI ON

>^ OF THE

UNIVERSITY

OF



NEW YORK

JOHN WILEY & SONS

London: CHAPMAN & HALL, Limited
1910



^



s^ai



etcuuEv

QENERAL



Copyright, 1910

BY

BURT E. NELSON



'SThc Scientific ^rcss
^abttt pi-ummunit ani> Company



PREFACE

The method for the proximate analysis of unknown
drugs and medicinal chemicals and mixtures has not
been dealt with in a general manner by any recent
work in the English language, although a number of
foreign treatises dealing with special classes of me-
dicinal compounds or drug constituents have appeared
within the last few years.

This neglect is no matter of wonder, as the majority
of investigators are interested in the more scientific and
economic problems dealing with the chemical constitu-
tion and possible methods of synthesis in the laboratory
of the members of the particular class of bodies with
which they are dealing, rather than in the methods
of separating these from all the sorts of possible com-
binations in which they reach the consumer. Partial
exceptions to this are the drug and chemical assays
which are made for evaluation or standardization pur-
poses, or with the object of detecting objectionable
additions, and which generally have to do with known
substances.

A more general work like the present, however, is
intended to furnish methods by which the student
or analyst who has not specialized in drug chemistry
may obtain information which is often desired by
Health Departments, the State, and the general public,
as possibly furnishing formulae by which unknown
medicines may be duplicated, or together with occasional
pharmacological experiments, indicating their relative

ill



20510



O



iv PREFACE

medicinal value and safety or danger for use by a lay
public. However medical ethics may regard propri-
etary mixtures, there is undoubtedly a legitimate
place in trade for the more reliable of them, providing
of course that they do not contain any actively potent
ingredients, or containing these state clearly their names
and amounts with a suitable caution to the consumer.

Here local Health and State authorities could un-
doubtedly exercise a control similar to that found in
some foreign countries, requiring and verifying for
each such mixture sold within its territory a fairly
complete statement as to its potent contents, the
records of which might be accessible to authorized
persons, and by excluding such as were found dangerous
or obviously fraudulent.

This work is now being pursued by the Drug Lab-
oratory of the United States Department of Agri-
culture, the Council on Pharmacy and Chemistry of
the American Medical Association, and to a less extent
by a few individuals.

Quite different from these proprietary mixtures,
most of which have a trade-marked name, are the true
patent medicines which are now used extensively by
the medical profession, and which for the most part
are definite synthetic chemical compounds having
known chemical and physiological properties. These
and mixtures of these and the commonly used medicinal
substances of the pharmacopoeias, which latter are
known as official medicines, are generally far the more
easy for the analyst to handle.

The following pages are intended less for the presenta-
tion of new matter or methods than for bringing to-
gether in an available form commonly used methods
and tests which the beginner, or analyst interested in



PREFACE V

other lines of work, could only obtain from various
sources.

Numerous errors undoubtedly exist, and many omis-
sions were made necessary by the small size of the
volume.

The tables of medicinal chemicals arranged in the
order of their melting points, boiling points, and car-
bon content have proved very convenient in routine
work, and these figures are largely relied upon in fixing
the identity of unknown bodies.

The pages on Systematic Microscopical Drug Anal-
ysis, together with a number of the illustrations of
ground vegetable drugs drawn from the microscope,
are from the author's articles, "An Analytical Scheme
for the Microscopical Analysis of Drugs," published
serially in Merck's Report from July, 1900, to August,
1907, inclusive, and to these articles those more inter-
ested in the subject may refer, as well as to the finely
illustrated works of Koch, " Mikroskopische Analyse der
Drogen Pulver," " Tschirch und Osterle," " Anato-
mischer Atlas der Pharmacognosies' and the English
work of Greenish.

As the work is intended to be elementary in nature,
considerable space has necessarily been given to the
methods of ordinary simple inorganic and organic
analysis, and to various commonly used apparatus
and operations. Credit is here given to the numerous
standard American and foreign works which have
been freely utilized.



CONTENTS



PAGE

Preface iii

CHAPTER I
Introduction i

CHAPTER II
Apparatus and Operations 5

CHAPTER III
Ultimate Inorganic Analysis .71

CHAPTER IV
Ultimate Organic Analysis 7^

CHAPTER V

Determination of Molecular Weights, Common Radi-
cles, and Chemical Formula 87

CHAPTER VI
/ / Principles of Drug Analysis. Methods 97

CHAPTER VII

[/ Analysis of Medicines Generally 133

vii



viii CONTENTS

CHAPTER VIII

PAGE

The Principles of Microscopical Drug Analysis 153

CHAPTER IX
Systematic Microscopical Drug Analysis 192

CHAPTER X

/ Assays of Chemicals, Crude Drugs, and Pharmaceuti-
cal Preparations 226

CHAPTER XI
y Pharmacological Methods 243



TABLES



PAGE

I. Systematic Table of Organic Drug Constituents and

Medicinal Chemicals 259

II. Elementary Organic Analyses of Medicinal Chemicals,

Arranged in the Order of their Carbon Content. ... 322

III. Melting-points of Commonly Occurring Medicinal

Chemicals and their Derivatives, Arranged in the
Order of their Magnitude 338

IV. Boiling-Point Tables 342

V. Alcohol Tables 343

VI. Table of Constants of Fats and Oils 344

VII. Table of Volatile Oils 346

VIII. Glycerin Tables 348

IX. Resins, Gum Resins and Balsams 349

X. Physiological Action of Some Common Drugs 351

XI. Table of the Elements 362

XII. Commonly Used Metric and English Equivalents. . . 364

Appendix. — Reagents 365

ix



LITERATURE

American Druggist
American Journal of Pharmacy-
Archives fiir Pharmacie

AuTENRiETH, Detection of Poisons and Strong Drugs
Bruhl, Die Pflanzen Alkaloide
Brickdale, An Introduction to Pharmacodynamics, Based on

the Study of the Carbon Compounds
Burton Sanderson, Laboratory Handbook of Physiological

Chemistry
Chemiker Zeitung

CusHNY, Pharmacology and Therapeutics
Czapek, Biochemie der Pflanzen
Coblentz, The Newer Remedies
Dieterich, Analyse der Harze
Dragendorff, Analyse von Pflanzen
Druggists' Circular

Euler, Grundlagen und Ergebnisse der Pflanzenchemie.
Fluckiger and Tschirch, Principles of Pharmacognosy
Fresenius-Cohn, Quantitative Chemical Analysis
Greene, Experimental Pharmacology
Guildemeister und Hoffman, Die Aetherischen Oele
HiLDEBRANDT, Ncucrc Arzneimittcl
Journal of the American Medical Association
Journal of the American Chemical Society
Journal of the Society of Chemical Industry
Journal of Biological Chemistry
Koch, Mikroskopische Analyse der Drogen Pulver
Leach, Food Inspection and Analysis
Lengerken, Handbuch Neuerer Arzneimittel
Lyons, Assaying of Drugs
Merck's Index
Merck, J ahresberichte

xi



xii LITERATURE

Merck's Report

Meyer, Analyse und Constitutionsermittelung organischer
Verbindungen

MuLLER, Pharmacognosticher Atlas

National Standard Dispensatory

New and Xon-OlTicial Remedies, Amer. Med. Ass'n.

Pharm. Zentralhalle

Pharm. Zeitung

PiCTET, Alkaloids

Pozzi-EscoT, Synthase et Constitution des Albumenoides

Proceedings of the American Pharmaceutical Association

Prescott, Organic Analysis

Proctor, Leather Industries Laboratory Book. (Tannins.)

RosENTHALER, Grundzugc der Chemischen Pflanzenunter-
suchiing

Sadtler, Industrial Organic Chemistry

ScHMiEDEBURG, Grundriss der Pharmacologic

Schmidt, Die Alkaloid Chemie

Sutton, Volumetric Analysis

TscHiRCH, Harze und Harzebehalter

TscHiRCH, Die Chemie und Biologic der Secrete

TscHiRCH und Oesterle, Anatomischer Atlas der Pharmacog-
nosie

United States Pharmacopoeia

United States Dispensatory

United States Department of Agriculture — Miscellaneous Bul-
letins

Van Rijn, Die Glycoside

Wiesner, Rohstoffe des Pfianzenreiches

Wiley, Foods and their Adulterants

WiNTON, Microscopy of Vegetable Foods



%'^ OF TH£

OF



Introduction to the Analysis of
Drugs and Medicines



CHAPTER I

INTRODUCTION

The chemical analysis of unknown medicinal mix-
tures entails difificulties fully as great as those found
in the examination of any other class of substances,
largely on account of the multitudinous array of pos-
sibly present bodies and because of the common presence
of many chemically indifferent substances having no
distinctive characteristics and separated with difficulty
from the much smaller portions of active recognizable
constituents. Also because of the extreme sensibility
of many of these to such physical agents as heat, oxida-
tion or the action of the necessary reagents. In many
instances it is impossible in the present state of our
knowledge to isolate and determine in a definite crys-
talline form, all of the proximate constituents from
a mixture as we would the elements in a mineral anal-
ysis. Moreover the complete composition of most
of our plant drugs is unknown.* Even granting the
good fortune to be able to accomplish this, there still

* The term drug is here used in its more restricted sense as
meaning a dried plant part in the crude state, as distinguished
from pure chemical substances which may be separated from it
(proximate principles) or prepared artificially.



2 ANALYSIS OF DRUGS AND MEDICINES

will frequently remain the chance for considerable
speculation as to the form in which some of these
principles was originally introduced.

For most practical purposes, however, this difficulty
is less of a drawback than might be expected because,
for example, in the case of a vegetable drug, by know-
ing the amounts of several active constituents, we
may from a knowledge of its normal composition
calculate very closely the amount of crude material
originally employed, e.g., having found a mixture to
contain 0.5 per cent of subcarbonate of bismuth and to
yield by appropriate treatment, traces of oil of cinnamon
(recognized by its odor), gum, resin, meconic acid,
and 0.006 per cent of crystallized morphine, and a small
amount of alcohol, it is fair to suppose that the original
was a mixture containing the bismuth salt mixed with
tincture of opium and cinnamon water.

From this example it may also be seen that a very
considerable help may be had from a knowledge of
the common uses of drugs and medicines, as well as
from an actual acquaintance with the sensible prop-
erties of the pharmaceutical preparations. It is often
possible for a skilled observer to obtain a clue to all
the bodies present in a mixture from its appearance,
taste, and odor, and no drug analyst could be con-
sidered thoroughly competent who had not acquired
this acquaintance by actual experience.

Frequently, too, experiments on the lower animals
may be resorted to with benefit, either for purposes
of directing the chemical search or for confirming the
results of it. Cocaine and most of the solanaceous
alkaloids possess the property of dilating the pupil
of the eye when dropped into the conjunctiva, and
the analysis of a mixture producing this action could



INTRODUCTION 3

not be considered correct which did not account for
it.

The small quantity of sample available for analysis
is often another serious obstacle. While very minute
quantities of inorganic substances may be identified
with certainty, it is nearly always necessary in the
case of organic ones to have an amount of sample
which will allow of their being separated in a pure
condition in quantity sufficiently large for allowing of
a determination of their solubilities, precipitation
and color reactions, melting or boiling points, and
frequently also of their ultimate analysis by com-
bustion in many cases.

Micro-chemical analysis and crystallography would
also seem to be particularly adapted to cope with the
problems presented here, if developed along these
lines, as they are in the case of inorganic substances,
but their pursuit would presuppose an amount of
specialized training which could hardly be expected
of the beginner. To those wishing to pursue this
branch as applied to the mineral salts and acids, the
work of Behren, " Mikrochemische Analyse," and par-
ticularly of Doctor E. M. Chamot as taught at Cornell
University, are to be recommended. Excellent articles
by the latter author appeared serially in the Journal
of Applied Microscopy mid Laboratory Methods from
January, 1900, and extending through several years,
but are now out of print.

It goes without saying that the analyst should ob-
tain full preliminary data regarding the uses, doses
and action of unknown mixtures wherever possible,
as such information if received from reliable sources
may save many hours of useless work.

In the case of preparations from vegetable drugs,



4 ANALYSIS OF DRUGS AND MEDICINES

the amounts of characteristic ingredients which may
be separated from them may be not only relatively
very small, but these latter are usually intimately
associated with many bodies which may be common
to whole classes of plants, as, e.g., tannins, resins, gums,
and the indefinite group commonly called extractives,
etc. Then too, the possible presence of added colors
and flavors must not be lost sight of. A former belief,
which empirically accredited useful medicinal prop-
erties to nearly every herb which grew, has left its
record in the large number of vegetable drugs of ques-
tionable utility and whose composition and action are
for the most part unknown, which are still in more
or less favor in many sections. The passing of this
and the contemporaneous polypharmacy of the past,
and the present tendency of physicians to rely on more
rational therapeutics, and to use a smaller number
of single, or at least mixtures of a few definite, com-
pounds whose composition and properties are known
and whose action on the animal economy can be
more accurately predicted, is now continually tending
to simplify the work as far as regularly used official
drugs and chemicals is concerned. Exceptions are the
various serums, vaccines, and other principles derived
from animal organs which are quite popular, as
are numerous other products of vital activity. The
investigation of these latter bodies naturally falls
within the scope of bacteriology and physiological
chemistry. Lastly, many preparations consist in part
at least of comminuted crude drugs, usually mixed
with a greater or less number of other substances.
Obviously purely chemical means will here often fail
to furnish means for identification, and our only re-
course is the information furnished by microscopic



INTRODUCTION 5

botany or pharmacognosy. Indeed it may be stated
as a rule that to obtain good results in this work,
chemistry, microscopy and experimental pharmacology
must go hand in hand.

From the foregoing it will be seen that for one to
thoroughly arm himself for the problems of this branch
of drug work, he must needs possess a fair working
knowledge of pharmacology and therapeutics, a thor-
ough familiarity with the sensible properties of the
commonly used pharmaceutical preparations, knowledge
of the various proximate constituents of organic drugs,
of the anatomical features by which these drugs may be
identified when in a powdered condition, and finally
with the methods of inorganic and organic analysis.
Even with this formidable equipment he will frequently
find his best efforts baffled. We are also in a position
to appreciate the natural limitations of the subject
matter, for as we are here chiefly interested in isolating
synthetics and natural proximate plant constituents,
and in identifying organized structures and simple
inorganic compounds, all investigation into the com-
position and atomic structure of these bodies them-
selves, methods for their artificial production in the
laboratory, and the laws governing their physical and
physiological behavior, etc., belong to other depart-
ments of science.



CHAPTER II
APPARATUS AND OPERATIONS

The room and furnishings for carrying on drug
analysis will from necessity vary with the circumstances.
In general it may be said that it should be equipped
with suitable tables, one of them preferably low for
microscopical work, a sink, and convenient water
supply having sufficient pressure to operate a jet pump
effectually, a fume closet having a good draught, and
racks or stands for supporting small apparatus.

In the way of apparatus itself, there will be needed
all of the smaller glass and porcelain pieces for carry-
ing on general inorganic analysis, including assorted
lots of beakers, flasks, evaporating dishes, crucibles,
test tubes, one or more desiccating jars, the latter
preferably having an attachment for exhausting the
air, a good balance sensitive to one-tenth milligramme,
burettes graduated to one-tenth cubic centimeter,
a series of pipettes holding from one to at least ten
cubic centimeters, volumetric flasks and graduated
cylinders holding from ten to one thousand cubic
centimeters, a water-bath drying oven and a convenient
water or steam bath for evaporations, etc.

In addition to these there will be needed a number
of pieces more common to organic chemical work.

Extractions in drug analysis may be applied to either
solids or liquids. The former may be treated by
simple maceration, by percolation, or by continuous
hot percolation in one of the forms of continuous ex-

6



APPARATUS AND OPERATIONS



tractors, while the latter are generally extracted in
stoppered separators or in continuously acting per-
forators as described below.

In extracting solids by maceration, all that is neces-
sary is to allow the powder to stand in a stoppered
flask or bottle with the solvent, occasionally agitating,
and to finally remove an aliquot portion of the clear
fluid for analysis.

In other cases the entire amount of solvent is occa-
sionally removed, the residue expressed, and treated
with fresh supplies of solvent until the marc is entirely
exhausted.

When extracting crude drugs by the former method
for assay or other purposes requiring quantitative
accuracy, an allowance and correction must be made
for the measured amount of menstruum absorbed by
the powder, and for the
volume of the latter in the
total mixture, before meas-
uring off the aliquot por-
tion. To avoid the error
of this correction it is well
to complete the extraction
of the powder by fresh
portions of solvent as just
described or to conduct the
entire operation in a suit-
able-sized percolator (Fig.
1, A) to this end a small
amount of cotton is forced
into the heck, the contents of the macerating bottle
shaken and transferred to it, rinsing out the bottle
with the first portions of percolate. The percolator
is now allowed to drain completely, a good-sized tuft




B



Fig. I.



8 ANALYSIS OF DRUGS AND MEDICINES

of cotton introduced, and the whole packed down
evenly so that the last portions of menstruum run through
very slowly, and the extraction then completed with
fresh portions of Hquid. When this process is used for
the entire operation the dry powder is introduced on
top of the first cotton plug and packed down sufficiently
with the last one, sufficient menstruum added to soak
through and thoroughly moisten the whole, the mass
again packed more tightly if necessary, and the opera-
tion continued to complete exhaustion with fresh men-
struum as before. As percolators, small glass syringe
barrels may be made to serve.

Percolation in the manner just described undoubtedly
furnishes one of the safest methods of extraction, as
it requires no heat and its thoroughness can be observed,
but it requires considerable time and attention and
for most operations of this character has been entirely
superseded by continuous hot extraction in an ap-
paratus similar to the Soxhlet shown in Fig. i, B.

The vapors from the liquid in the boiling flask ascend
through the side tube, and after being condensed above
the liquid falls back into the apparatus, penetrates
the powder, which is either loosely packed in the body
of the tube or loosely tied in a cotton bag, and accu-
mulates until it reaches the level of the bend in the
small siphon tube, when it is again automatically
emptied back, together with its contained extracted
matters, into the flask.

This apparatus is intermittent in action, the same
portion of solvent remaining in contact with the powder
until siphoned off. Numerous other forms are con-
tinuous acting. A convenient one of this latter type
which is easily constructed is shown in Fig. i, C It
consists of a filtering tube connected with a boiling



APPARATUS AND OPERATIONS



flask below and a condenser above. The powder to
be extracted is loosely contained in a cotton cloth or
open-ended tube, and by the side of either of these is
placed a short section of small glass tubing through
which the ascending vapors may pass.

As an amount of heat sufficient to operate any of
these forms of apparatus with solvents
boiling above 60° C. is bound to be
frequently detrimental, it will be found
advantageous to supply them with a
capacious condenser above, which is
surmounted by an air chamber and
trap. In this way a slight vacuum
may be maintained by the jet pump,
which allows of the various solvents
boiling at a lower temperature, and
also prevents the escape of vapors from
any leaky joints should such occur.
Care must of course be used to see
that the suction is not sufficiently
strong to carry the ascending vapors
entirely through the condenser before
they have had time to become cooled.
A form of extraction apparatus which
the author has used for larger quan-
tities of drugs for special purposes, is
constructed entirely of copper and
works on the same principle. In this the powder rests
in perforated trays. Fig. 2.

Evaporation in the ordinary round-bottomed dishes
heated by direct heat is as a rule only suited for the
handling of inorganic bodies and others which are
known to be stable. For most vegetable or animal
medicinal materials this amount of heat would be




Fig. 2.



10



ANALYSIS OF DRUGS AND MKDICINES



entirely too severe and recourse must be had to sponta-
neous evaporation, either in a draft of air or in a des-
iccator over calcium chloride or sulphuric acid, or to
evaporation in a partial vacuum.

For the spontaneous evaporation in the air, broad
flat-bottomed glass dishes of the type known as crys-
tallization dishes or deep Petri dishes will be found
best suited, although an ordinary beaker will answer.

These dishes of various
sizes will also be fre-
quently required for crys-
tallizations.

In evaporating very
volatile liquids from
heavy liquids or solids
Dragendorff 's dry -air cur-
rent desiccator (Fig. 3, B)
will be found useful. The
longer of the two tubes
in the bell jar extends
nearly to the liquid in the
dish while the exit tube
just reaches through the
cork. The air may be
drawn through the ap-
paratus by means of a filter pump or, what is pref-
erable, forced through from an air blast. In either
case the air should be first sent through one or more
towers containing granular calcium chloride, and a dish
containing this may well be kept in the bell jar, which
latter is made tight on the ground-glass base by means
of tallow or other grease. The air current evaporates
the light liquid with but little loss to the heavier bodies.
The drying materials are for the purpose of removing




Fig. 3.



APPARATUS AND OPERATIONS 11

all moisture from the air, which would otherwise be
deposited on and in the dish owing to the cold pro-
duced by the evaporation of the light liquid. The
time at which the Hght solvent is all blown off may
usually be determined by the absence of odor in the



Online LibraryBurt Everette NelsonIntroduction to the analysis of drugs and medicines; an elementary handbook for the beginner → online text (page 1 of 25)