AMORPHOUS ALKALOIDS OF PERUVIAN BARK.

BY VIRGIL COBLENTZ, PH. G.

Query No. 7. What are the various so called amorphous alkaloids of Peruvian bark of the market?

The preparation of cinchona barks into various eligible forms to meet the many wants of a general consumption, has been the study of the pharmaceutical profession for many years. Until of late, the alkaloids of the bark have been too expensive, where it was demanded in large quantities and among the poorer classes. To meet this difficulty and yet furnish a product of almost equal efficacy to the quinine itself, at but a fractional cost, has been many times attempted. As an example of this attempt, the government of India in order to furnish as cheap and economical a febrifuge as possible having almost the equivalent power of the quinine, manufactured a crude mixture of the alkaloids for use among the native hospitals; by exhausting the bark successively with dilute HCl and precipitating the total Alkaloids in an impure state with NaOH, further purified by being deprived of the larger proportion of its coloring matter. As a fair representation of this we have at present in the market about three of these so-called amorphous alkaloids, severally known as dextroquinia, quinquinia and powdered purified chinoidine.

QUINQUINIA. The label of quinquinia claims thus: "This preparation contains 15 per cent. quinine, the remainder consisting of the other alkaloids of chinchona bark in their natural combinations.”

DEXTROQUINIA.—Composition, C40H6N4O3.

DEXTROGYRATE WITH POLARIzed Light.—This article is prepared from the residual mother liquor from the true red and other high grade cinchona barks, and consists essentially of the amorphous quinine of Liebig. It is equal to sulph. quinine in the same dose, and is a thoroughly reliable and economical substitute for this valued alkaloid.

PURIFIED CHINOIDINE. (Prepared by McK. & R.) Containing all the uncrystalized alkaloids of the cinchona bark. Similar preparations have been lately offered in the market at high prices, under different fancy appellations and claims made for the same as of equal efficiency of quinine. As a great demand exists for a cheap anti malarial remedy, this preparation is introduced at low figures, about one-eighth the price. of sulph. quinine.

From these statements it appears that the preparations are composed of anhydrous alkaloids mixed in variable proportions with chinoidine, the residue remaining after separation of the crystalizable bark alkaloids from solution. These samples were numbered, but not in order mentioned and then examined qualitatively and quantitatively.

1.

QUALITATIVE EXAMINATION.

Moisture-One grain of the powder was carefully dried at 100° C. until it ceased to loose weight.

2. Solubility-A 1 grain sample was treated with excess of alcohol, heated and allowed to stand and the residual matter if there was any, filtered off on a tared filter, washed, dried and weighed. A like sample was treated under like circumstances with diluted alcohol.

3. Reaction-A small portion of the powder was placed on a piece of moistened red litmus, after remaining a time the alkalinity, if any, was noted by blue color.

4. Non Volatile Compounds—A portion of the powder was digested with water for twenty-four hours and filtered. The solution evaporated to dryness and incinerated in a platinum capsule.

5. Sulphates-Portion of powder dissolved in water acidulated with HCl treated with BaCl, for H2SO4.

6.. Ammonia Salts-Portion of powder treated with boiling alcohol, filtered and the residue washed with hot alcohol. (Residue A, filtrate-B.)

(A). Treated with hot water, filtered and BaCl, added for H2SO 4• Portion of solution was heated in a test tube with liquor potassa and a piece of moist red litimus held in contact with vapor, (being turned blue if ammonia be present.) Also, a glass rod moistened with acid was held in tube, giving heavy white fumes if NH, be present.

Filtrate (B). Alkaloids-The hot alcoholic solution deposited on cooling crystals, which were collected on a filter.

(B1). Quinia—Filtrate evaporated to dryness, residue dissolved in acidulated water, precipitated with ammonia, then shaken with ether; etherial solution evaporated. The residue treated with chlorine water and ammonia as thalleioquine test for quinia.

(B2). Cinchonine-The crystals deposited on cooling the hot aicoholic solution (B) were digested with H2O filtered and washed. (The solution a, residue crystal b).

(a).

To the solution NH4OH was added as test for cinchonine. (b). The crystals which were undissolved by the digestion with H2O (B2) were dissolved in dilute HCl tested for quinia and quinidia and if these were not present tested for cinchonine by NH4OH.

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Quinia and Quinidia-A portion of the powder was dissolved in dilute acid precipitated by sol. NaOH and shaken with ether fortior; the etherial residue was tested for quinia and quinidia. Portion was dissolved in dilute alcohol, acidulated slightly with H2SO, and tincture iodine added, the bulky brown precipitate was redissolved by aid of gentle heat; after standing twenty-four hours the deposit was examined. The quinidia being recognized by the presence of the brown iodosulphate of quinidia, and the quinia by the characteristic green-black crystals of harapathite.

In making a quantitative examination of the different alkaloids contained in these powders, it was first attempted to dissolve the powder in a dilute acid and precipitate the alkaloids entire by NaOH and then separate them quantitatively, and, while considering that these are alkaloids of some degree of purity, and not having the difficulties to contend with as in the crude bark, one would be led to think a simple method like this would be sufficient; other methods similar to this were tried, but always with some difficulty, that of resinous and coloring matters interfering by sticking to the sides of the beaker with the alkaloid. The method of the U. S. P., for assaying the cinchona barks, in ⚫ part was then adopted giving the most satisfactory results. The process was that with which you are all familiar, consisting in main part of mixing two grams (the official proportion) of the powder with five grams of lime (slaked) dried and exhausted with alcohol, alcoholic solution acidulated with dilute H2SO, and addition of a small quantity of water evaporated until all the alcohol was driven off, then filtered, washing filter with diluted H,SO, and then placing the solution of alkaloids in an accurately fitting glass stoppered bottle, and shaken with an excess of purified chloroform; when thoroughly mixed, sufficient solution of NaOH was added to set all the alkaloids free; it was then vigorously shaken five

minutes or more and, while still mixed by the shaking, poured upon a filter, well wetted with chloroform, placed over a tared flask; the bottle was rinsed with a little CHCl, and poured upon the filter; when the CHC1, was nearly drained off the aqueous mixture was carefully returned to the bottle, and again well shaken with CHCl, and returned to filter as before. The chloroformic solution was evaporated to dryness in a water bath, and the flask dried in an oven at 100° C. till of constant weight. This gives total anhydrous, crystallizable and uncrystallizable alkaloids. The lime was used to combine with, and fix the coloring matters, and precipitation by soda, but shaking with CHCl, before adding the soda, since by precipitation with NaOH portions of the alkaloids were lost by adhering to the sides of the capsule with small portions of resinous matter; and since all the alkaloidal matter was removed by a thorough shaking with chloroform, this mode of separation was adopted. As for a quantitative separation, the method of DeVry was adopted as follows: "To the total quantity of the mixed alkaloids resulting from each assay, was added a small quantity of tolerably fine powdered glass, and ten times the weight of the alkaloids, in ether fortior, the flask was corked and vigorously shaken, until by means of the glass all the alkaloids were detached from the flask and ground up in the presence of the ether in fine particles." By this operation the alkaloids are separated into two parts, one (A) soluble in ether and (B) insoluble in ether. The part soluble in ether contains the quinine and the amorphous alkaloid, together with traces of quinidine; while the insoluble part contains the cinchonine, cinchonidine and quinidine. These two parts are separated by filtration, the insoluble portion washed with a little ether and the etherial solution evaporated.

A.-(Part soluble in ether). The ether having been evaporated and the residue dried at 100° C., this may in many instances be practically considered as consisting simply of quinine, but as the estimation of quinidine and amorphous alkaloid is desired, the residue is dissolved in