.411

1.365

ah. 040

a Deviated more than 10 per cent from the average of all. Mechanical shaker used in extracting the drug.

Iodeosin indicator used.

In shaking out, the solution was washed with the volatile solvent before making alkaline.

d Difficulty in decanting 100 cc as directed in extracting the drug.

• Less than 100 cc decanted, but calculated to 100 cc.

ƒ Powdered pumice used to assist filtration of extract.

9 In shaking out, the chloroform was filtered through a small plug of purified cotton in
the stem of the separator. The alkaloidal residue was dissolved in 2 cc of ether. The
standard acid added and ether expelled by warming before titrating the excess of acid.

No good end reaction was obtained. Alcohol distilled over alkali was employed as
neutral alcohol. In a blank experiment it titrated slightly alkaline. Not included in

average.

The alkaloidal residue was dissolved in 1 cc of neutral spirits, excess of standard acid added and titrated back with limewater. A blank was run with the same amount of acid and indicator.

* Hematoxylin indicator used.

In extracting the drug the ether mixture was allowed to stand with the drug 10 minutes, with frequent agitation before adding ammonia.

Paper pulp used to assist filtration of extract.

n The alkaloidal residue did not form a clear solution with acid.

• Fifty cc extra ether-chloroform mixture used to extract the drug.

P Twenty-five cc extra ether-chloroform mixture used to exhaust the drug.

9 Seventy-five cc extra ether-chloroform mixture used to exhaust the drug. In the
final shaking out five portions of 25 cc each of ether were employed.

The mixture was decanted into a small percolator provided with a pledget of purified
cotton in the neck, the upper orifice being then loosely corked.

The directions for Method II, as originally given in Bulletin 107, were followed.

* Residue was redissolved and reextracted with ether; yield, 0.312.

u Residue was redissolved and reextracted with ether; yield, 0.315. Forcible expression was used to obtain 100 cc of solution.

COCA LEAVES.

This sample, delivered as No. 60 powder, passed through the several sieves in the following proportions:

A large portion of the powder was coarser than the pharmacopoeial requirement for assay samples of this drug. The gravimetric results by Method I (U. S. P.) are too few to justify any conclusions. Of the volumetric results, 36 per cent come within 10 per cent and 58 per cent within 15 per cent of the average. Of the gravimetric results by (II), 75 per cent come within 10 per cent and 82 per cent within 15 per cent of the average. Of the volumetric results, 33 per cent come within 10 per cent and 72 per cent within 15 per cent of the average. The gravimetric averages and likewise the volumetric averages by the respective methods are in substantial agreement, the gravimetric results being somewhat higher than the volumetric, owing probably to impurities in the alkaloidal residue. In (I) Mr. Fuller accomplished the final shaking out with three portions of 20 cc each of ether instead of 25, 20, and 15 cc. He thinks the drug should be digested with the solvent mixture longer than one hour, as the marc in this case still contained alkaloid. Mr. Hankey dissolved the alkaloidal residue with 1 cc of “neutral spirits" and titrated with acid and diluted limewater as with belladonna root. Cochineal gave an unsatisfactory end reaction. Messrs. La Wall and Parker noted considerable emulsification in shaking out by both methods. The latter used 50 cc more solvent than is directed for percolating the drug, and J. G. Francis used 75 cc more, and shook the drug finally with five portions of 25 cc of ether. The extraction was not complete.

For coca as for belladonna the amount of solvent mixture directed in the United States Pharmacopoeia method is scarcely adequate for the proper manipulation and extraction of the drug. In the final shaking out process further extraction with ether is desirable. In (II) Mr. Blome suggests increasing the ether-chloroform mixture to 180 cc and decanting 120 cc. Mr. Hankey obtained a better end reaction with iodeosin than with cochineal. Professor La Wall obtained equally low results in a duplicate assay. J. G. Francis found that the final extraction was not complete. Mr. Pearson could not decant 100 cc without forcible expression, and therefore objects to the method. As in (I), further extraction with ether in the final shaking out is probably desirable.

In both (I) and (II) considerable impurity evidently passes into the alkaloidal residue, and a more thorough washing with solvent before making alkaline is indicated.

THE MACROSCOPY AND MICROSCOPY OF DRUGS.
By H. H. RUSBY.

The object of this brief paper is to direct the attention of the members to the importance of chemists supplementing their chemical methods by suitable physical methods in identifying and estimating drugs; and to the facility with which the chemist can acquire enough knowledge of such physical methods, and of the physical properties of drugs, to be of great assistance in his analytical work.

When the subject of the chemical standardization of vegetable drugs was being agitated in connection with the approaching United States Pharmacopœia Convention of 1890, the writer was astonished to hear Prof. John M. Maisch declare himself

opposed to the introduction of such standards into the Pharmacopoeia. This surprise was considerably augmented when Doctor Maisch gave as his reason the statement that if a man knew drugs as he should it would not be necessary to examine them chemically to determine their quality. Although we can not in these days admit the propriety of neglecting chemical standardization, for this or any other reason, yet subsequent experience has shown that Doctor Maisch's claim to be able to judge the quality of drugs without recourse to chemical methods is largely justified.

The necessity of such knowledge is apparent when we reflect that of the 167 crude vegetable drugs of the Pharmacopoeia, chemical standards are prescribed for only 22, and yet the Pharmacopoeia does not recognize more than one-half of the nonstandardized articles in common use. It is true that chemists employ quantitative methods, all more or less satisfactory, in the case of ten or a dozen others, which are not thus treated in the Pharmacopoeia. Admitting these to full membership, how overwhelming still is the majority upon the other side! Let it not be said that the nonassayable list represents only unimportant drugs. It is one of the great temptations of the chemist to underrate subjects with which he does not deal, and he is apt to reason post hoc, ergo propter hoc. Let us not forget that it is the extreme variability in activity of such drugs as veratrum, digitalis, ergot, and cannabis indica, coupled with their exceeding importance in medicine, which has forced a resort to physiological standardization, applicable as yet to but few drugs. It is this tendency to vary in quality and our general inability to estimate such quality that has to a great extent destroyed the usefulness of some drugs which would otherwise be generally relied upon. As illustrations, let us note male fern, spigelia, cusso, and other anthelmintics, Winter's bark, coto bark, and chrysarobin. The importance of the drugs named is relatively greater than that of the assayable ones, by virtue of the fact that the latter can be substituted by their proximate principles, while the former can not. There is yet another element of weakness in the chemical assay of drugs, which is greatly mitigated by attention to their macrosopical and microscopical characters. Every assayer is frequently more or less chagrined by the thought that after all he does not know what it is that he has in hand after he has extracted the full required percentage of alkaloid by the prescribed method, since part of it may have been extracted from an admixture. Impurities in drugs, either from accident or design, may and frequently do fail of detection by the chemist, even in the case of freely assayable drugs, where detection would be simple by intelligent physical examination before assaying.

Even the great array of unofficial and unimportant drugs can not be dismissed from the chemist's ken because of their want of substantial therapeutic activity. They are in common use and some one pays for them the money which is his property and which entitles him to the receipt of what he pays for. He may be deprived of the protective aid of the Pharmacopoeia without having his legal or professional rights in any degree curtailed. Indeed, the chemist himself is a deeply interested party in this class of transactions. Every commercial chemist will admit that some of his most profitable work lies in the field of the unofficial materia medica, and where the distinctly chemical indications are usually indefinite and faint. It seems quite unnecessary to argue further that a knowledge of the physical identification characters of vegetable drugs is of great service to the chemist. Is it too much to say that the field of success thus opened to him is far greater, as to crude vegetable drugs, than that which he can control by chemical methods alone? I feel very sure that such a statement is just and moderate.

This being so, how far can macroscopical and microscopical methods supply the deficiency? And how great an expenditure of effort and time does it require? It may be admitted at once that to secure an expert knowledge of this subject requires the same kind and degree of application that it does to become an expert chemist, but it is at the same time true that a very moderate amount of effort, intelligently

and judiciously applied, will add more to the general efficiency of the chemist than the same amount applied in any other direction. I believe that no chemist should proceed with the chemical examination of a drug of this class until after he has examined it physically, with or without the microscope, according to the requirements of the case, to ascertain its general characters and particularly whether it is a single article or a mixture. This requires a fair knowledge of macroscopy and microscopy, as to both methods and drugs. The time and labor necessary to acquire such a knowledge are not excessive. As to all the official and important unofficial drugs, it should be gained by from one hundred to one hundred and fifty hours of practical work, say two or three hours per week during a two-year course.

The following examples will serve to illustrate the class of drugs to which reference is here made: Coto and paracoto bark are among the most reliable therapeutic agents in the materia medica, often the only means of saving life in severe cases of dysentery, yet the use of this medicine has almost ceased owing to the fact that the genuine drug is now scarcely ever seen. In two years the writer has not known of an importation of it to the United States that was not spurious. A brief macroscopic examination will enable anyone immediately to recognize every one of these pretenders. The same statement applies, in a somewhat less serious degree, to Winter's bark, a most valuable aid in nutrition.

The belladonna invoice covers a multitude of fatal and dangerous imperfections. A very large part of our belladonna root contains poke root, not only an exceedingly active poison but an article that counteracts the medicinal effect of belladonna. It is sometimes difficult to distinguish the smaller roots by macroscopical means, but the dust in the package will always show, under the microscope, the needle-shaped crystals of the poke root. The same statement applies to an admixture of poke leaves to belladonna leaves. Scopola leaves are often mixed with and substituted for belladonna leaves. This is liable to destroy the life of the patient receiving the medicine. In any case the medicinal actions of these two are antagonistic. Some indication of the identity of these plants is almost always present with the leaves; for example, the belladonna has black berries, while the scopola has pale yellow circumscissile pods, and the two can be instantly distinguished.

A spurious henbane sometimes contains from ten to fifteen times as much alkaloidal matter as the genuine and has a different action. These alkaloids are so poisonous that they are given in doses of only one two-hundred-and-fiftieth to one one-hundredth of a grain. Imagine the effect of giving a dose containing fifteen times as much as it should. When powdered, the spurious can be recognized by its stellate hairs and by certain cells with wavy thick walls. Henbane and digitalis may contain stramonium leaves. Any considerable amount of such an addition to digitalis must put the life of the patient in danger, because with heart failure life often depends upon the full and prompt action of the latter remedy. Here the microscope is almost necessary, as a single hair from the leaf of the stramonium, densely covered with minute warts, will tell the story.

Strophanthus seed is another drug of great service in heart failure, and used when promptness is necessary. There is one variety of the seed which produces no good effect, and there has been ten times as much of this used in the United States as of the other, because it has cost only one-tenth to one-fifth as much. During the past year the use of the spurious kind has been largely stopped. The two seeds have such different macroscopic characteristics that they can not be mistaken when once the difference has been noted.

So-called saffron is frequently found which consists of marigold flowers, colored red with anilin and heavily weighted with mineral matter. The evil result of this fraud is peculiar. Saffron is largely used for giving an agreeable color to medicinal preparation, so it is added to medicines in a prescription. This mineral matter is