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uary,

Result: Bright-red mixture giving at the end of ten minutes no reactions for alkaloids.

Experiment (b). The solution of brucine was rotated while the nitric acid mixture was being added, so as to thoroughly mix the acids immediately on coming in contact.

Result: Water-white mixture which had a faint yellow tinge after 24 hours.

Brucine recovered at end of that time 0.91 gramme, i. e., 91 per

cent.

Experiment (c). The nitric acid mixture was added in a haphazard manner and beaker rotated as directed in the official process. Results: Various, usually the mixture remained colorless, sometimes it became red.

Farr and Wright suggested heating the solution of alkaloids to 122° F. before adding the nitric acid. Accordingly these experiments were repeated at that temperature.

The results were the same as before; experiment (a) gave a red liquid; (b), a colorless mixture which remained so over night, and (c) a mixture red or colorless, as luck would have it.

The foregoing experiments were repeated, using different samples of nitric acid; those containing traces of hyponitric acid affected the brucine much more readily than an acid strictly pure.

Kebler and Hoover found traces of this impurity in two out of four samples of C.P. nitric acid they examined."

Besides the various methods of adding the nitric acid, the absence, or varying proportion, if present, of the lower oxides of nitrogen may possibly account for the astonishing lack of uniformity in the results of different operators. The presence of the lower oxides of nitrogen in nitric acid, either as an impurity or as the first product of the reaction, is often necessary to start the nitration of organic compounds. In the experiment (a) by allowing the strong nitric acid to remain in contact with the brucine solution this desideratum is obtained. It seemed reasonable to infer from this, that if the preliminary reduction of the nitric acid were prevented, the production of di-nitro-brucine would not take place. Accordingly a few drops of hydrogen peroxide solution were added to a portion of the acid solution of brucine, and the strong nitric acid mixture was trickled

U. S. Dept. of Agriculture, Bureau of Chemistry, Bulletin 99, page 191.

. Jour. Pharm

down the side of the beaker. It formed a distinct colorless layer at the bottom which showed no trace of color in several hours.

To another portion of the brucine solution I c.c. of a solution of sodium nitrite was added. A reddish tint developed slowly, since, as pointed out by Lunge," pure nitrous acid does not affect brucine. A few drops of solution of hydrogen peroxide added to the above mixture produced a bright-red color immediately by partially oxidizing the nitrous acid into nitric acid and other oxides of nitrogen. From these reactions we concluded that the most suitable reagent for nitrating the brucine would be nitric acid containing a fair proportion of the lower oxides of nitrogen in solution.

We therefore modified the U.S.P. process by substituting fuming nitric acid (commercial nitrous acid S.G. 1.42) for the U.S.P. nitric acid (S.G. 1·40) and extending the period of contact to 30 minutes in order to insure destruction of the whole of the brucine at various temperatures. The results were as follows:

Inasmuch, however, as commercial nitrous acid is unstable and of varying composition, we considered it desirable to discard its use in favor of U.S.P. nitric acid and sodium nitrite. By these reagents the following results were obtained with pure alkaloids :-

These results show that the U.S.P. process modified in this way is accurate over a wide range of temperature when pure alkaloids are employed. It has been observed that any impurity in the mixture of total alkaloids from nux vomica has a tendency to retard the nitration of the brucine. Again if, as has been suggested, there is a

10 Ztschr. f. angew. Chem., 1902, No. 1.

third alkaloid in nux vomica it may not be a negligible factor so that deductions from experiments with pure alkaloids cannot wholly be applied to the total alkaloids obtained in the usual way.

Different portions of 10 c.c. of the fluid extract (mentioned before) were operated on by the usual method until the total alkaloids were obtained. These were subjected to the process, detailed below, then the alkaloidal residue was extracted and titrated. To overcome the objections to experimenting with unknown quantities of alkaloids, and to thoroughly test the process, the alkaloid was again extracted after the above nitration, subjected a second time to the nitrifying agent under same conditions as before, then extracted and titrated. The results are given below.

The process was then applied to the fluid extract of nux vomica without preliminary extraction of the alkaloids, 10 c.c. was evaporated to dryness in a beaker. The resulting extract was dissolved, as far as possible, in 15 c.c. 3 per cent. H2SO, and treated with nitric acid and sodium nitrate in the usual way. At end of 30 minutes the mixture was diluted with 20 c.c. water, run through a pledget of cotton wool, then filtered and followed by wash water. The bulked liquid was put in a separator, made alkaline with KOH solution, and extracted by means of chloroform. The alkaloid was obtained in definite crystals having a yellow tinge, but otherwise free from impurity. The titration indicated 0-1072 gramme, which closely agrees with figures above.

Evidently, then, the process is not affected by the purity of the alkaloidal residue. We have already shown that it is applicable over a wide range of temperature, and is not affected by any possible manner of adding the reagents or probable impurity therein. Subsequent use in the routine work of the laboratory justifies these conclusions.

Adding our modifications to the text of the U.S.P., the following gives the process in detail:

-"dissolve the alkaloidal residue in 15 c.c. of 3 per cent. H2SO. To this solution add 3 c.c. of a mixture of equal volumes of nitric

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,

acid (S.G. 1-4) and distilled water, then add 1 c.c. of a 5 per cent. solution of sodium nitrite in water, and, after rotating the liquid a few times, set it aside for exactly 30 minutes, stirring it gently three times during this interval." The solution is then made alkaline and shaken out with chloroform in the usual way.

91 FULTON STREET, NEW YORK.

THE FOOD AND DRUGS ACT, JUNE 30, 1906, AND ITS EFFECT ON THE COMPOSITION OF MEDICINE.1

BY H. W. Wiley.

The food and drugs act introduces for the first time into this country a national control over interstate and foreign commerce in foods and drugs. The importation of foreign drugs is controlled at the ports of entry under an existing law which was first enacted in 1848. This law not having been specially repealed, I believe, under the ordinary construction, remains in full force except in points in which its provisions are in conflict with those of the new inspection law. Just how far the requirements of the new inspection law must be read into the old law is a matter of purely legal character on which I have no opinion. It is evident, therefore, that the application of the act, in so far as drugs are concerned, will be practically to the control of domestic commerce.

Two standards for drugs entering into interstate commerce are specially noted in the act, namely, standards as set forth or indicated in the U.S.P. and the N.F.; second, standards which are placed on the drugs themselves. Under the terms of the act it appears that any drug bearing a name recognized in the U.S.P. or N.F. shall be held to conform in strength and purity to the standards therein established or indicated, whether they are marked U.S.P., N.F., or not. If it is desired that these drugs shall conform to any other than that of the established authorities, this standard must be plainly stated upon the label.

Drugs which are used for technical purposes are evidently not included in this classification, inasmuch as the definition of drugs. excludes all chemicals and all drugs ordinarily so used, employed.

'Read at the Philadelphia Branch of the American Pharmaceutical Associaion, December 12, 1906.

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for technical purposes. This is so clearly brought out in the law itself, it appears to me, as to need no further elucidation, yet some questions have been raised respecting a discrimination. As a mere suggestion I would say that when substances are used both for medicinal and technical purposes, it would be advisable to state upon the label the fact that they are to be used "for technical pur. poses," when so intended, or to attach some other word so as to show clearly that they are not to be used as drugs. In regard to certain kind of substances, the law presents a double attitude. illustration of this is in the case of alcoholic products. When these are used as beverages it is not necessary to state upon the label the quantity of alcohol which they contain. If, however, prescribed as remedies or drugs, tonics, or otherwise, the label must bear the required statement.

A question arises here of some importance in regard to these bodies. If the physician prescribes wine as a tonic the patient may purchase this wine either of a liquor dealer or a druggist, and the same is true, for instance, in the case of malt extract which may be sold as indicated above or over the bar. When is an article purchased as above to be considered as a beverage and when a medicine? Here is a question of such nice legal bearings that I am unable to give any opinion. Theoretically any such package should bear the percentage of alcohol therein contained; practically it would be rather difficult to enforce such a regulation.

The most striking feature of the Food and Drugs Act is that relating to the practical exemption from supervision, as to standards, of the so-called proprietary remedies. Just why the U.S.P. and N.F. remedies should be subjected to such a rigid standard and practically the same mixtures be allowed to go uninspected, when in the guise of a patent medicine, is a question of importance. This is no more strange, however, than the laws regulating the practice of medicine and pharmacy. Those who are legitimately engaged in the practice of these professions are required to take a long course in preparatory training and to secure a license after examination before State and Municipal Boards in medicine and pharmacy, and even then they are required to practice their professions under the strict supervision of the law. On the other hand, the quack doctor or the proprietor of a fake remedy may practice medicine through the public press and dispense drugs