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For the assay of extract of nux vomica the Pharmacopoeia directs that 2 Gm. of the extract, dried at 100° C. (212° F.), be dissolved in a mixture of 10 Cc. of alcohol and 5 Cc. each of 10 per cent. ammonia-water and plain water. To this solution contained in a separator are added 20 Cc. of chloroform and the mixture shaken for five minutes. After complete separation the chloroform layer is drawn off into a beaker or an Erlenmeyer flask, and 5 Cc. of chloroform having been added to the contents of the separator without mixing, is also drawn off into the beaker for the purpose of washing the outlet tube of the separator. The extraction with two further portions of chloroform of 15 Cc. each and washing of the outlet tube as before, is repeated. The united chloroformic solutions are evaporated in a beaker or flask at a moderate heat, and to the residue is added from a burette 10 Cc. of decinormal sulphuric acid, and then 20 Cc. of hot water. When solution has been effected, 2 Cc. of Brazil-wood test solution is added, and centinormal potassium hydroxide solution then run in until a permanent pinkish color is produced by the action of a slight excess of alkali on the indicator. The number of Cc. of centinormal alkali solution required is divided by 10, the quotient subtracted from 10, and the remainder multiplied by 0.0364 and that product by 50 (or the remainder multiplied at once by 1.82), which will express the percentage of total alkaloids in the sample, it being assumed that brucine and strychnine are present in equal proportions.

Much annoyance may be averted by adding 5 Cc. of alcohol to the liquid in the separator before the second and third additions of chloroform, for the prevention of emulsions.

Fluid extract and tincture of nux vomica may be assayed in the same manner as the extract, after they have been evaporated to a nearly solid consistence, 10 Cc. of the first-named preparation or 100 Če. of the last-named being used for each assay.

If the determination of strychnine alone is preferred for the extract, fluid extract, or tincture, the present official method of assay may be modified, as explained above under the assay of the crude drug, except that in the case of the extract the weight of the final dry residue must be multiplied by 50 instead of 10, in order to express the percentage of strychnine present, while in the case of the fluid extract it should be multiplied by 10, and in the case of the tincture by 1, to express the amount of strychnine present in 100 Cc. of the respective liquids.

ASSAY OF OPIUM.

The morphiometric assay of opium directed in the Pharmacopoeia is generally known as Squibb's method, and is a modification of the method first suggested by Flückiger. Ten Gm. of opium, preferably in fine powder, is exhausted by shaking actively and frequently with 100 Ce. of cold water in a well-corked flask during six or eight

hours. The mixture is then poured on a 5-inch filter, allowed to drain, and the residue percolated slowly with cold water until 150 Ce. of fluid have been collected. The mare is returned to the flask, briskly shaken for ten or fifteen minutes with 50 Cc. of water, poured back into the filter, allowed to drain, and again percolated with water until 150 Cc. more of fluid have passed through into a separate beaker; finally, a further portion of 20 Cc. of percolate is collected. The second or weaker percolate is evaporated on a waterbath, in a tared dish, to a syrupy consistence, the first percolate is added, the beaker being rinsed with the third percolate, and the whole evaporated, without stirring, to a weight of 14 Gm. The liquid is transferred to a tared flask of 100 Cc. capacity, and the dish rinsed with several small portions of cold water until the liquid in the flask weighs 20 Gm. Now add 10 Gm. of alcohol, rotate the flask so as to mix the liquids, add 25 Cc. of ether, cork well, mix the liquids thoroughly, and finally add 3.5 Cc. of 10 per cent. ammonia-water, after which shake the flask briskly for ten minutes and set aside in a cool place for six hours or over night.

Pour off the ethereal layer carefully, wash the contents of the flask twice with 10 Cc. of ether by careful rotation, so as to avoid an emulsion, for the purpose of removing as far as possible the original ethereal fluid and the ether-soluble matter contained therein; then pour the contents of the flask into a small double filter (two counterpoised filters, one inside of the other), rinse the flask with small quantities (2 or 3 Cc. each) of cold water, pouring this also on to the filter, and wash the filter and contents repeatedly with cold water until practically free from color, after which wash with 5 Cc. of morphine-saturated alcohol and then with 10 Cc. of ether, by delivering the liquid drop by drop from a pipette to the edges and contents of the filter. Finally, dry the filters and contents to constant weight at 60° C. (140° F.) and multiply the weight of crystals by 10, to obtain the percentage of crystallized morphine (hydrated) in the opium.

Morphine, being present in opium chiefly as sulphate, is readily extracted with water; but along with it other substances, such as codeine, narceine, coloring-matter, inorganic salts, etc., are also brought into solution, which it is intended to remove entirely or retain in solution by the addition of alcohol and ether when the precipitation of morphine is finally effected. As pure morphine is not entirely insoluble in water, a dilute mother-liquor is undesirable; hence concentration of the infusion is resorted to in order to reduce the loss from this source; the addition of alcohol has been found advantageous in preventing the precipitation of much coloring matter along with the morphine, and is by no means hurtful in the proportion directed. The ether removes codeine and other ethersoluble alkaloids, and, moreover, by its saturation of the aqueous fluid, still further reduces the solvent power of the latter on the freshly precipitated morphine. The addition of the ammonia-water

decomposes the morphine salt in solution, and the free alkaloid gradually separates in the form of crystals, which separation is materially aided by actively shaking the flask for ten or fifteen minutes. Morphine crystallizes with one molecule, or 5.94 per cent. of water, which it loses very slowly and imperfectly at the temperature of a boiling water-bath.

As it is easier to render the crystals anhydrous by heating for two or three hours at 110° to 115° C. (230° to 239° F.) than to maintain the temperature during drying at 60° C. (140° F.), as directed in the Pharmacopoeia, this plan is preferred by many, and in that event the weight of anhydrous crystals must be multiplied by 1.063 to obtain the weight of crystals containing one molecule, or 5.94 per cent. of water of crystallization.

When the tincture and wine of opium, and also tincture of deodorized opium are to be assayed, 100 Cc. of the respective liquids are evaporated on a water-bath to about 20 Cc.; the residue is mixed with 40 Cc. of water, thoroughly mixed, and set aside for an hour, occasionally stirring, to get rid of resinous matter. The mixture is then filtered, the filter and residue well washed with water until all soluble matter is extracted, and the washings and filtrate evaporated to a weight of 14 Gm. From this point the process is identical with that described above for opium.

For the assay of vinegar of opium 100 Cc. of the liquid also are used; but as the preparation is acid it is first neutralized by the addition of 4 Gm. of calcium carbonate, or such a quantity as may be necessary, and the process then carried out as described above.

In the case of extract of opium 4 Gm. of the extract dried at 100° C. (212° F.) is dissolved in 30 Cc. of water, the solution filtered through paper, and the filter and residue washed with water until all soluble matters have been taken up. The filtrate and washings are evaporated to a weight of 10 Gm., transferred to a 100 Cc. Erlenmeyer flask, and made up to 15 Gm.; then add 7 Gm. (or 8.5 Cc.) of alcohol, shake well, add 20 Cc. of ether, and shake again. Now add 2.2 Cc. of ammonia-water to the contents of the flask, and continue the process as directed under opium. The final weight of crystals multiplied by 25 represents the percentage of crystallized morphine present in the sample of extract.

If the assay of opium, or any of its preparations, has been carried out with care the impurities possibly present in the crystallized morphine obtained are likely to be counterbalanced by the loss of morphine during the process by solution in the mother-liquors.

The amount of impurities present may be determined either by treatment of the morphine with fresh lime water, in which pure morphine is soluble to the extent of 1 part in 100, or the alkaloid may be dissolved in an excess of decinormal acid and the excess of acid titrated with centinormal alkali in the presence of hæmatoxylin solution as an indicator. Each Cc. of HSO, will neutralize 0.0303 Gm. of morphine containing 1 molecule of water of crystallization.

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CHAPTER LXII.

NEUTRAL PRINCIPLES AND GLUCOSIDES.

BESIDES organic acids and alkaloids, plants furnish a number of valuable principles which have a neutral reaction, and, for convenience, are divided into bitter principles and glucosides, the former being also known as amaroids. The distinguishing feature of the latter class is that when treated with diluted acids or ferments they split up into glucose, and a new body, differing from the original substance acted upon, but characteristic of that substance. With very few exceptions, glucosides do not contain nitrogen. Although glucosides are an important group of plant-products, only one is officially recognized in the Pharmacopoeia, partly due to the fact that they do not always constitute the active principle of the plant, and are in many cases associated with other bodies. A few glucosides appear to have a dual character, for, while yielding glucose by the treatment above mentioned, some also possess basic and others acid properties. As stated in a previous chapter, both glucosides and bitter principles are distinguished from alkaloids by the ending

in or inum.

The following official neutral principles are used by physicians to a greater or less extent: Aloin, chrysarobin, elaterin, glycyrrhizin, picrotoxin, salicin, and santonin; of these, salicin is a true glucoside.

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Aloin. The name aloin is used, both commercially and in the Pharmacopoeia, to designate the neutral, bitter, crystalline principle of aloes, irrespective of the source, although the Pharmacopoeia does specify two varieties, namely, that derived from Barbadoes and Socotra aloes.

It is more than probable that a very large proportion of the aloin sold in this country is derived from Curaçoa aloes, as this variety is much richer in aloin than either Barbadoes or Socotra aloes, and, moreover, comparatively little of the latter variety reaches this market. Cape aloes, which was formerly supposed not to contain any crystalline aloin, has been shown to contain the same, and the name capaloin has been given to it. Tschirch in 1898 succeeded in crystallizing capaloin from alcohol and ether in the form of colorless needles.

Various methods have been proposed for the manufacture of aloin, the best known of which is the treatment of aloes with hot water acidulated with either hydrochloric or sulphuric acid; after the infusion has been allowed to stand for a day it is carefully (737)

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decanted from sediment, concentrated at a moderate temperature, and set aside, when crystals or crystalline crusts of aloin will separate. The aloin may then be purified by recrystallization from hot water or very dilute alcohol. The addition of a little acid has been found advantageous in avoiding the contamination of aloin with noncrystallizable matter, which is less soluble in acidulated water than in plain water.

A more recent method suggested by Schaefer depends upon the property of aloin of forming very difficultly soluble compounds with the alkaline earths in ammoniacal solution, which, upon decomposition with an acid, yield aloin. The following method for determining the aloin content in aloes indicates the process of manufacture for aloin on a large scale: 50 Gm. of aloes are mixed with 300 Cc. of hot water, with the addition of a few drops of hydrochloric acid. On cooling the solution is decanted from the separated resin, mixed rapidly with 50 Cc. of 20 per cent. ammoniawater and a solution of 15 Gm. of calcium chloride in 30 Cc. of water. The precipitate is collected after fifteen minutes, the water expressed, and the lime salt decomposed by triturating it in a mortar with a slight excess of hydrochloric acid. The resulting mixture of aloin and calcium chloride is then dissolved in a small quantity of hot water, filtered, the filter washed with hot water, and the aloin crystallized out at a low temperature with the aid of ice. As much as 30 per cent. of aloin in fine, light-yellow crystals has been obtained from commercial aloes by this method.

The average yield of aloin from the different commercial varieties of aloes varies from 4 to 20 per cent. and over.

Aloin owes its value as a laxative to a substance known as emodin, with which it is associated in aloes and into which it is in all probability converted by the alkaline intestinal fluids. If aloin be treated with ether, any emodin present will be extracted, aloin being insoluble in ether. The peculiar color reactions, from orange to deep cherry-red, observed when 5 per cent. ammonia-water is shaken with an ethereal extract, obtained from a decoction of aloes by agitation with ether, are due to emodin; pure aloin, freed from emodin, fails to show these colors.

Aloin of commerce is often contaminated with resinous and other matter, which can be detected by imperfect solubility of the sample in cold water. As stated in the Pharmacopoeia, barbaloin differs from socaloin in yielding with cold nitric acid a crimson color; heat must not be used in this test, as socaloin, when heated with nitric acid, gives similar results.

Chrysarobin. This principle, derived from Goa Powder by treatment with hot benzene, is frequently confounded in commerce with chrysophanic acid. As thus obtained it is still contaminated with some impurities, but corresponds to the requirements of the Pharmacopoeia; it can be obtained pure, in the form of small yellow

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