commonly received theory be true, that it is made by a fermentation process, in which impure malic acid is concerned,-we can readily understand how viscid organic matter may be present in sufficient quantity to produce the result alluded to.

In addition to the preparations of Turkey opium, we have also had the opportunity of experimenting on small quantities of the Patna, Malwa, and Persian varieties, and all of them present peculiarities of interest. An aqueous extract and a tincture have been made from each, and from the Patna sort sufficient has remained to make a specimen of liquor.

The most striking fact in connection with the whole of them is the existence of large quantities of codeine. In the extract of Patna opium (Plate IV. fig. 1) it is the chief crystalline constituent, and though the liquor (Plate II. fig. 6) shows abundance of the other opium principles, it evidently owes its narcotic effect much more to codeine than Turkey opium does. We have the experience of an opium eater on this point; he states that the quantity required to produce the effect is larger, but there is less discomfort in the after effects than with other sorts. Malwa opium (Plate IV. fig. 2 and 5) shows more narcine and narcotine, but in the tincture we have in addition to a mass of minute crystals, certain larger prisms, which are probably codeine. Persian opium (Plate IV. fig. 3 and 6) also evidently contains a large proportion of narcotine and codeine.

We stated at the commencement that this must be looked upon only as a preliminary research, there remaining many points on which our information is far from complete. In continuing the inquiry we intend to devote ourselves chiefly to the elucidation of certain particulars. Firstly, the condition or form of combination in which morphine exists in crude opium; secondly, the relation of extract of poppy to opium in respect to crystalline principles; and thirdly, the influence which the extractive matters may have in altering the crystals obtained in opium solutions, and the variations of the normal forms induced by this cause.

The general conclusions we have arrived at in addition to a knowledge of the appearances presented by typical and special preparations of Turkey, Patna, Malwa, and Persian opiums, are mainly these:

That tincture, most nearly of any of the preparations, represents the properties, good and bad, of the crude drug.

That when crude opium is taken up with proof spirit as in tincture, the resin separates on evaporation.

That the preparations which have held their ground with the public and the medical profession, in spite of price, differ from the tincture in comparative freedom from resin and narcotine, and in containing only a diminished quantity of meconic acid.

That in the preparation of extract of opium it is important to use a large quantity of distilled water to ensure the separation of narcotine and resin. That when extract of opium is dissolved in water, filtered and evaporated again to an extract a second or third time, the crystals frequently differ considerably from those seen in the normal or first formed extract.

That when extract of opium is taken up with rectified spirit 56° O.P., and evaporated again to an extract, crystallization does not take place, or only to a very trifling extent.

That morphine and its salts, and perhaps other opium principles, do not crystallize readily from their solution in wine.

Finally, it remains for us to express our obligation to our friends Mr. Morson, of London, and Messrs. T. and H. Smith, of London and Edinburgh, for the courteous way in which they have assisted us with specimens, when working upon those of the alkaloids which exist only in minute quan

tities in opium; without this assistance we could scarcely have procured them in a state of reliable purity.

In some remarks which followed the paper, the authors drew the attention of the meeting to a new alkaloid procured from opium by Messrs. T. and H. Smith, a specimen of which they were enabled to lay before the meeting through the kindness of the discoverers. They stated that for want of time and sufficient quantity to work upon, the Messrs. Smith had not yet determined its chemical composition nor all of its reactions, but exhibited to the members present the brilliant colour-reactions which the minutest quanti ties yielded, viz. :-a deep blue on treating with concentrated sulphuric acid, turning rapidly to bright green on the addition of a small crystal of nitrate of potash.

2. Narcotine.

3 a. Sulphate of Morphine.

b. Meconate of Morphine.

ba. Commercial salt crystallized from solution in weak alcohol. bb. Crystallization from mixed solutions of Morphia and Meconic Acid.

Fig. 1. Tinctura Opii (Turkey Opium), prepared by the Authors as standard. 2, 3. Specimens of Tincture alluded to in the text.

4. Extractum Opii (Turkey).

5 a. Commercial Extract of Opium, imported.

b. The same, re-dissolved, filtered, and evaporated.

6. Liquor Opii Sedativus, prepared from Patna Opium.

PLATE III.

Liquor Opii Sedativus (Turkey Opium).

Fig. 1. Battley's.

2 a, b. Two specimens prepared by the authors by slightly different processes, from different samples of opium.

3. Mr. Morson's, alluded to in the text.

4, 5, 6. Specimens sent out by three operative chemists of standing in

London.

REPORT ON THE PURITY OF SULPHATE OF QUININE OF COMMERCE.

BY MR. W. WALTER STODDART.

(Read at the Bath Meeting of the British Pharmaceutical Conference, Sept. 1864.) Probably quinine is one of the most important therapeutic remedies for the ills of the human body that has ever been introduced to the notice of the medical man; so extensively is it used, and with such certainty may its effects be calculated, that no other substance can be advantageously substituted. Yet this very circumstance unfortunately gives the temptation for frauds and adulterations so commonly said to be practised by unprincipled dealers.

The smallness of the dose with which quinine gives such remarkable results, renders any sophistication all the more dangerous, and disappointing to the physician; indeed, the very turning-point of an illness may be frequently dependent on the purity of a sample of quinine.

It is not by any means to be supposed that any suspicion is attached to the high respectability and probity of the well-known manufacturers of quinine. Existing adulterations, properly so called, such as the deliberate addition of salicine, sugar, boracic acid, quinidine, cinchonine, etc., are only made by second or third-rate dealers, or when it has passed through the hands of a third or fourth party. Such samples may still be found in shops situated in secluded parts of the country or lowest streets of a city, and traceable to the same origin. On the other hand, probably from difference in the mode of preparation or separation of the cinchona alkaloids, quinine differs much from the presence of its isomeride quinidine. The latter is often, if not always associated with quinine in the natural state, and has many of its reactions exactly similar, besides being nearly as soluble in the usual menstrua.

It therefore becomes to a certain extent a natural mixture, and in proportion to the completeness of the extracting process, so will be the purity of the product. Opinions, it is true, vary greatly as to whether quinine and quinidine differ in their medicinal power, and therefore some may say that the presence of the latter (quinidine) is of no consequence; this, however, is not the question at issue, and the points of this report are strictly confined to the commercial purity of quinine and its freedom from the cheaper salts.

In carrying out this object the desired results are threefold:

First, Qualitative, or to find an easy and reliable test for the presence of the three most common cinchona alkaloids, quinine, quinidine, and cinchonine.

Secondly, Quantitative, to find the most practical and reliable mode of separating and estimating these alkaloids; and,

Thirdly, an application of the above to the examination of the sulphate of quinine as made by the principal manufacturers.

Although the cinchona barks contain many alkaloids, only four occur in sufficient frequency and quantity to merit notice in a commercial investigation, quinine, quinidine, cinchonine, and cinchonidine. In actual practice the two last may be estimated together.

The most prominent impurity in quinine is quinidine; in none of the aftermentioned samples was cinchonine discovered in any quantity except one. The slight solubility of the cinchonine salts as compared with those of quinine and quinidine, and the boldness of its crystallization would, to the practised eye, soon lead to its detection; experiments will easily show the truth of this, and that quinidine and not cinchonine must be generally sought as the chief impurity in commercial sulphate of quinine.

Notwithstanding tests for the purity of quinine are so numerous and in some instances so trustworthy, still few apply to the separation of quinidine from

VOL. VI.

T

quinine; nearly all are proposed for the indication of quinine only, or its detection when mixed with other substances.

The polariscope tests of Bouchardat and Pasteur, and the fluorescent test of Professor Stokes, require too much study and practice to come into general use for qualitative analysis among manufacturers and retailers.

The same remarks apply to the exquisitely beautiful experiments of Dr. W. B. Herapath. It is quite true that to the expert the iodine test will detect the presence of a very minute portion of quinine, quinidine, or cinchonidine, yet it requires considerable experience with an expensive polarizing microscope, with great consumption of time, to give good results, when only a minute quantity is operated on.

The chlorine and ammonia test of Brande, and the chlorine test of Pelletier, will not distinguish always between quinine and quinidine.

The presence of so much water and ammonia is detrimental to the British Pharmacopoeia test, which is anything but a good modification of Liebig's original one.

From these remarks it will be apparent that a good qualitative test for detecting the several cinchona alkaloids in an unknown mixture is a desideratum. From a considerable series of experiments it appears that these conditions may be amply fulfilled by either of the two following methods.

The first is a modification of that proposed by Liebig.

Into a glass tube or bottle put ten grains of the suspected 'salt, dissolve in ten minims of dilute sulphuric acid and 60 minims of distilled water; to this add 150 minims of pure sulphuric ether, three minims of alcohol, and 40 minims of a solution of hydrate of soda (1 part to 12 parts). Agitate well and lay aside for twelve hours, when if the slightest trace of quinidine, cinchonine, or cinchonidine be present, they will be seen at the line of separation between the ether and solution of sulphate of soda.

If only a small percentage of quinidine be present, it will appear as an oily substratum, appearing under the lens as dust from the minuteness of its particles. Cinchonine will appear more decidedly crystalline. With a little practice, the eye will easily distinguish which of the alkaloids is deposited.

This will detect a much less quantity of quinidine than the Pharmacopoeia test. In the latter the ether dissolves a greater portion of the quinidine, while the dilute ammoniacal solution of sulphate of ammonia is an actual solvent unless great care be taken to add no more ammonia than will exactly precipitate the alkaloids, which is often difficult and tedious.

The second method proposed is the one most generally used by the author, and which is perhaps the easiest and most trustworthy of any hitherto submitted. The reagent is sulphocyanide of potassium.

Into an ounce of distilled water drop ten drops of dilute sulphuric acid (British Pharmacopoeia). To this add 14 grains (or as much as will saturate the acid) of the suspected salt. Filter through paper, and to a little of the filtered solution add a few drops of the solution of sulphocyanide of potassium (180 grains in 1 ounces of water). An immediate precipitate of the several alka. loids takes place, each of which, as seen by the sketches, is distinct and characteristic.

If quinine, quinidine, and cinchonine be present they will all be seen on the slide distinct from each other, becoming more so every minute.

A very good plan is to place a very small drop on a glass slip and to put another of the sulphocyanide by its side. Over both place a piece of thin glass, which will cause the drops to touch. Examine the line of junction under a quarter-inch lens, when the crystals are scen and may be readily recognized. By this method of a grain of quinidine or cinchonine may easily be detected.

10000

It is very interesting to see the particles all arranging themselves into the respective groups; the long slender needles of the quinine salt, the round crystalline masses of the quinidine, and the large well-formed prisms of the cinchonine

salts. So remarkably constant is this reaction, that an observer who has once been accustomed to the general appearance can at once say with ease, this is quinine, this quinidine, and that cinchonine.

Sulphocyanide of potassium is not usually kept by druggists, but may readily be made thus:

Cyanide of potassium (fused),

Sublimed sulphur, of each 120 grains.
Distilled water, an ounce and a half.

Boil in a glass flask for fifteen minutes, filter, and make up the quantity to 1 ounces with sufficient distilled water.

This notice of the qualitative analysis ought not to be passed without mentioning a very good application of Professor Stokes's fluorescent test for the discovery of quinine and other substances possessing the property of epipolism.

A small Geissler's vacuum tube is surrounded by a longer glass tube which is capable of being closed by a cork, an arrangement that permits the tube to be filled and emptied as an ordinary phial bottle. When any bark is suspected to contain quinine, etc., an acid or alcoholic infusion is put into the outer tube, and a spark from the Ruhmkorff's coil passed through. Instantly the fluorescent salt, whatever it may be, will show its presence in the most gorgeous manner.

By this method twenty-seven samples of barks were qualitatively tested in a couple of hours that were supposed to contain a new alkaloid, which occurs in an Australian tree possessing very peculiar fluorescent properties.

The process most applicable for the quantitative analysis of sulphate of quinine is that by means of the iodide of potassium reaction, recommended by Dr. De Vry some time since. The following was the arrangement employed in the present instance:

Into a tube containing 120 minims of distilled water and 16 minims of dilute sulphuric acid (British Pharmacopoeia), add twenty grains of the sulphate of quinine to be tested. When dissolved add 80 minims of solution of hydrate of soda (1 to 12) and 300 minims of pure sulphuric ether mixed with six minims of alcohol.

Agitate well, and lay aside for twelve hours; decant the ethereal solution and evaporate for the quinine. To the remaining aqueous solution add just sufficient acetic acid to neutralize the alkali, and precipitate with solution of iodide of potassium (1 to 4), filter, dry, and weigh the hydriodate of quinidine. One hundred grains of this salt contain 71.68 of pure quinidine. To the filtered solution again add hydrate of soda till decidedly alkaline, when the cinchonine and cinchonidine will be precipitated if present.