ON THE ADULTERATION OF SULPHATE OF QUININE, AND THE MEANS OF DETECTION.

Mr. Zimmer, manufacturer of sulphate of quinine in Frankfort-on-the-Maine, has published the following circular and paper to his correspondents abroad:

Frankfort-on-the-Maine, Feb. 6th, 1852.

You are doubtless, aware that various and partly spurious kinds of sulphate of quinine have for some time past found their way into the market. The substance now frequently {143} mixed with quinine is quinidine. But little positive is as yet known of the medicinal properties of this alkaloid, and whatever may be the result of future experiments, its arbitrary substitution is, under any circumstances, unwarrantable, and renders all fair and honest competition almost impossible.

The importance of the subject has induced me to address a few words to you, that I may submit a simple experiment by means of which the most usual adulterations of quinine may readily be detected.

I have the honor to be, with much respect, &c.
C. ZIMMER.

The high price of genuine Bolivian Cinchona Calisaya, through the monopoly of its export, has given occasion to imports, from other districts, of Cinchonas, the quality of which widely differs from that of the Calisaya, inasmuch as they contain principally quinidine. The lower prices of these barks, regardless of their different constituents, have brought them quickly into use in many factories of quinine, whereby a large quantity of quinine, containing quinidine, has got into the market, causing an undue depreciation in the price of quinine.

The existence of this third cinchona-alkaloid is now established beyond a doubt by ultimate analysis, by the peculiarity of its salts, and by important distinctive tests; and there can be no further question, that quinidine must, equally with cinchonine, be distinguished from quinine. The external characters of sulphate of quinidine differ from those of sulphate of quinine; it has a greater specific gravity and less flocculent cry­stal­li­za­tion. In dry warm air it parts with its water of cry­stal­li­za­tion, without deliquescing or losing its crystallized aspect; lastly, it is far more soluble than sulphate of quinine in cold water and in alcohol.

One of the distinctive properties of the three alkaloids in question, viz., their behavior with ether—places in our hands a ready means of detecting the mixture of cinchonine and {144} quinidine, with quinine. Schweitzer (Lond. Med. Gazette, vol. xxi., p. 175) has already employed ether for the detection of cinchonine with complete success, and his process has, with justice, been subsequently quoted in most manuals, as it answers its purpose completely; cinchonine is known to be entirely insoluble in ether, whatever may be the quantity of ether employed. The solubility of quinidine in ether, as compared with that of quinine, is but slight; ten grains of pure sulphate of quinine dissolve in sixty drops of ether, and twenty drops of spirit of ammonia, while only one grain of sulphate of quinidine is soluble in the same quantity of the fluid; and in proportion quinine containing quinidine will always be less soluble than pure sulphate of quinine.

Guided by this fact I can recommend the following simple and very convenient process for the detection of quinidine and quinine:—

Ten grains of the salt to be examined is to put into a strong test tube, furnished with a tight-fitting cork, to this are to be added ten drops of diluted sulphuric acid, (one acid and five water) with fifteen drops of water, and a gentle heat applied to accelerate the solution. This having been affected, and the solution entirely cooled, sixty drops of officinal sulphuric ether with twenty drops of spirits of ammonia, must be added, and the whole well shaken while the top is closed by the thumb. The tube is then to be closely stopped and shaken gently from time to time, so that the bubbles of air may more readily enter the layer of ether.

If the salt examined be free from cinchonine and quinidine, or contain the latter in no greater proportion than ten per cent., it will be completely dissolved; while on the surface, where contact of the two layers of clear fluid takes place, the mechanical impurities only will be separated (in which respect the various sorts of commercial quinine differ.) After sometime longer the layer of ether becomes hard and gelatinous, after which no further observation is possible.

From the above statement respecting the solubility of {145} quinidine in ether, it appears that the ten grains of the salt to be examined, may contain one grain of quinidine, and still a complete solution with ether and ammonia may follow; but in this case the quinidine will shortly begin to crystallize in the layer of ether. The last trace of quinidine may be yet more definitely detected by employing, instead of the ordinary ether, some other, previously saturated with quinidine, by which means all of the quinidine contained in the quinine must remain undissolved. It is particularly requisite in performing this last experiment to observe, after the shaking, whether all has dissolved, for owing to the great tendency of quinidine to cry­stal­li­za­tion, it may become again separated in a crystalline form, and be a source of error.

If more than a tenth of quinidine or cinchonine be present, there will be found an insoluble precipitate at the limits of the two layers of fluids. If this be quinidine, it will be dissolved on the addition of proportionately more ether, while cinchonine will be unaffected.

It is expressly to be remarked, that the necessity for testing sulphate of quinine, in search of other fraudulent adulterations is not superseded by the above described process.

We have particularly to determine upon the absence of inorganic substances, which may be effected by subjecting to red heat on a platinum dish, or simply by solution in alcohol. Gypsum, chalk, magnesia, &c., will be left undissolved. Boracic acid will be dissolved by alcohol, but its green flame will indicate its presence in the alcoholic solution when ignited.

The absence of organic substances, such as salicine, sugar, stearic acid, &c., may be inferred from the formation of a colorless solution with pure concentrated cold sulphuric acid; it is as well to leave the sulphuric acid to act for some hours.

The presence of sal-ammoniac may be detected by the addition of caustic potash to the suspected salt, when, if present, it will be known by the diffusion of the ammoniacal odour.—Phar­ma­ceu­ti­cal Journal, March, 1852.

{146}

REMARKS ON THE ENVELOPEMENT OF PILLS. BY DORVAULT.

The envelopement of pills is a minute question, an accessory in this form of administering medicines, but as it is a frequent cause of trouble to practitioners, and as their successful operation is often due to their peculiar mode of exhibition, we shall perhaps be pardoned for devoting a short space to the subject.

In order that pills may not adhere to one another, they are rolled in an inert powder, such as marsh-mallow, liquorice, and above all, lycopodium. Carbonate of magnesia is now particularly used for pills of turpentine and copaiba. To disguise the peculiar odour of the pill mass, German practitioners use iris powder, or cinnamon.

To render pills more pleasing to the eye, as well as to disguise their taste, instead of rolling them in the before named powders, they are frequently covered with gold or silver leaf. The mode of doing this is too well known to need repetition. We will only remark that those pills which contain iodine, bromine, sulphur, iodides, bromides, sulphides, salts of mercury, gold, platina, &c., cannot be silvered.

These methods conceal but imperfectly the unpleasant taste and smell of certain pillular compounds. M. Garot, to obviate this inconvenience, has proposed to cover pills with a layer of gelatine, by means of a process which he has made public, and into the details of which we think it needless to enter. The gelatinous layer conceals the bad taste and smell perfectly, but it is attended with one inconvenience; in time it shrinks, cracks, and the pill mass exudes. Besides, much skill is required in its manipulation. After gelatinization comes sugaring. This is frequently preferable to the former modes, and can be equally well applied to pills of a repulsive taste and smell, (copaiba, turpentine, musk, assafœtida, &c.,) or to those which are changed by air or light, (proto salts of iron,) or deliquescent, (iod-hydrargyrate of iodide of potassium,) or caustic, (croton oil.) It can extemporaneously be performed in the following manner:—Put the pills into a vase with a round bottom, {147} or into a box lined with silver, moisten them with a little syrup of sugar, clear mucilage, or white of eggs, agitate them so as to moisten them uniformly; add a mixture of equal parts of gum, sugar and starch; again rotate them, so as equally to enclose all the pills. If a first layer be not sufficient, add a second and third in the same manner. Dry them in the air or in a stove. In damp weather, these pills should be enclosed in corked bottles. Gelatine of carragheen or caseine dried and powdered may be substituted for the above powdered mixture. This method is more expeditious than gelatinisation, and it has besides the advantage of the material being always perfectly soluble. Collodion has been proposed for enveloping pills, but seems never to have been used.

The last method we shall call toluisation. It appears to possess many decided advantages over the others. M. Blancard, its originator, employs it particularly for pills of proto iodide of iron. It is to induce its more general use that we make these remarks. The following is the mode of proceeding, which can be modified to suit the daily wants of practice:

Dissolve one part of balsam of tolu, in three parts of ether, (the balsam which has been used in the preparation of syrup of tolu will answer perfectly;) pour some of this tincture into a capsule containing the pills, to favor the evaporation of the ether. When the pills begin to stick together, throw them on a mould of tin passed through mercury, or simply on a plate, taking care to separate those which stick together. Set them in the air to dry. The drying may be completed in a stove of moderate heat, especially if several layers have been found necessary. This mode of enveloping may take the place, or nearly so, of all the others. An important point in it, is, that it resists the effects both of damp and dryness on the pill mass. Its balsamic odour is generally agreeable; but should it not be so, the tolu might be replaced by some inert resin soluble in ether, as mastic tears for example. The layer of resinous matter is so thin, that we apprehend no obstacle in its influence on the medicine. {148}

We will, however, make one general remark, namely: that as each method possesses some peculiar advantages, we thought it right to give them all.—Bulletin Gen. Ther. Med. et Chir. January, 1852.

ON THE APPLICATION OF ORGANIC CHEMISTRY TO PERFUMERY. BY DR. A. W. HOFFMAN. Professor to the Royal College of Chemistry, London.

Cahours’ excellent researches concerning the essential oil of gaultheria procumbens (a North American plant of the natural order of the Ericinæ of Jussieu,) which admits of so many applications in perfumery, have opened a new field in this branch of industry. The introduction of this oil among compound ethers must necessarily direct the attention of perfumers towards this important branch of compounds, the number of which is daily increasing by the labors of those who apply themselves to organic chemistry. The striking similarity of the smell of these ethers to that of fruit has not escaped the observation of chemists; however, it was reserved to practical men to discover by which choice and combinations it might be possible to imitate the scent of peculiar fruits to such a nicety, as to make it probable that the scent of the fruit is owing to a natural combination identical to that produced by art; so much so, as to enable the chemist to produce from fruits the said combinations, provided he could have at his disposal a sufficient quantity to operate upon. The manufacture of artificial aromatic oils for the purpose of perfumery is, of course, a recent branch of industry; nevertheless, it has already fallen into the hands of several distillers, who produce sufficient quantity to supply the trade; a fact, which has not escaped the observation of the Jury at the London Exhibition. In visiting the stalls of English and French perfumers at the Crystal Palace, we found a great variety of these chemical perfumes, {149} the applications of which were at the same time practically illustrated by confectionery flavored by them. However, as most of the samples of the oils sent to the Exhibition were but small, I was prevented, in many cases, from making an accurate analysis of them. The largest samples were those of a compound labelled “Pear oil,” which, by analysis, I discovered to be an alcoholic solution of pure acetate of amyloxide. Not having sufficient quantity to purify it for combustion, I dissolved it with potash, by which free fusel oil was separated, and determined the acetic acid in the form of a silver salt.

0,3080 gram. of silver salt = 0,1997 gram. of silver.

The per centage of silver in acetate of silver is, according to

Theory.Experiment.
64,6864,55.

The acetate of amyloxide which, according to the usual way of preparing it, represents one part sulphuric acid, one part fusel oil, and two parts of acetate of potash, had a striking smell of fruit, but it acquired the pleasant flavor of the jargonelle pear only after having been diluted with six times its volume of spirits of wine.

Upon further inquiry I learned that considerable quantities of this oil are manufactured by some distillers, from fifteen to twenty pounds weekly, and sold to confectioners, who employ it chiefly it flavoring pear-drops, which are nothing else but barley-sugar, flavored with this oil.

I found, besides the pear-oil, also an apple-oil, which, according to my analysis, is nothing but valerianate of amyloxide. Every one must recollect the insupportable smell of rotten apples which fills the laboratory whilst making valerianic acid. By operating upon this new distillate produced with diluted potash, valerianic acid is removed, and an ether remains behind which, diluted in five or six times its volume of spirits of wine, is possessed of the most pleasant flavor of apples.

The essential oil most abundant in the Exhibition was the pine-apple oil, which, as you well know, is nothing else but the butyrate of ethyloxide. Even in this combination, as in {150} the former, the pleasant flavor or scent is only attained by diluting the ether with alcohol. The butyric ether which is employed in Germany to flavor bad rum, is employed in England to flavor an acidulated drink called pine-apple ale. For this purpose they generally do not employ pure butyric acid, but a product obtained by saponification of butter, and subsequent distillation of the soap with concentrated sulphuric acid and alcohol; which product contains, besides the butyric ether, other ethers, but nevertheless can be used for flavoring spirits. The sample I analyzed was purer, and appeared to have been made with pure butyric ether.

Decomposed with potash and changed into silver salt, it gave

0,4404 gram. of silver salt = 0,2437 gram. of silver.

The per centage of silver in the butyrate of silver is according to

Theory.Experiment.
55,3855,33.

Both English and French exhibitors have also sent samples of cognac-oil and grape-oil, which are employed to flavor the common sorts of brandy. As these samples were very small, I was prevented from making an accurate analysis. However, I am certain that the grape-oil is a combination of amyl, diluted with much alcohol; since, when acted upon with concentrated sulphuric acid, and the oil freed from alcohol by washing it with water, it gave amylsulphuric acid, which was identified by the analysis of the salt of barytes.

1,2690 gram. of amylsulphate of barytes gave 0,5825 gram. of sulphate of barytes. This corresponds to 45,82 per cent. of sulphate of barytes.

Amylsulphate of barytes, crystallized with two equivalents of water, contains, according to the analysis of Cahours and Kekule, 45,95 per cent. of sulphate of barytes. It is curious to find here a body, which, on account of its noxious smell, is removed with great care from spirituous liquors, to be applied under a different form for the purpose of imparting to them a pleasant flavor. {151}

I must needs here also mention the artificial oil of bitter almonds. When Mitscherlich, in the year 1834, discovered the nitrobenzol, he would not have dreamed that this product would be manufactured for the purpose of perfumery, and, after twenty years, appear in fine labelled samples at the London Exhibition. It is true that, even at the time of the discovery of nitrobenzol, he pointed out the striking similarity of its smell to that of the oil of bitter almonds. However, at that time, the only known sources for obtaining this body were the compressed gases and the distillation of benzoic acid, consequently the enormity of its price banished any idea of employing benzol as a substitute for oil of bitter almonds. However, in the year 1845, I succeeded by means of the anilin-reaction in ascertaining the existence of benzol in common coal-tar-oil. In his essay, which contains many interesting details about the practical use of benzol, he speaks likewise of the possibility of soon obtaining sweet scented nitrobenzol in great quantity. The Exhibition has proved that this observation has not been left unnoticed by the perfumers. Among French perfumeries we have found, under the name of artificial oil of bitter almonds, and under the still more poetical name of “essence de mirbane,” several samples of essential oils, which are no more nor less than nitrobenzol. I was not able to obtain accurate details about the extent of this branch of manufacture, which seems to be of some importance. In London, this article is manufactured with success. The apparatus employed is that of Mansfield, which is very simple; it consists of a large glass worm, the upper extremity of which divides in two branches or tubes, which are provided with funnels. Through one of these funnels passes a stream of concentrated nitric acid; the other is destined as a receiver of benzol, which, for this purpose, requires not to be quite pure; at the angle from where the two tubes branch out, the two bodies meet together, and instantly the chemical combination takes place, which cools sufficiently by passing through the glass worm. The product is afterwards washed with water, and some diluted solution of carbonate of {152} soda; it is then ready for use. Notwithstanding the great physical similarity between nitrobenzol and oil of bitter almonds, there is yet a slight difference in smell which can be detected by an experienced nose. However, nitrobenzol is very useful in scenting soap, and might be employed with great advantage by confectioners and cooks, particularly on account of its safety, being entirely free from prussic acid.

There were, besides the above, several other artificial oils; they all, however, were more or less complicated, and in such small quantities, that it was impossible to ascertain their exact nature, and it was doubtful whether they had the same origin as the former.

The application of organic chemistry to perfumery is quite new; it is probable that the study of all the ethers or ethereal combinations already known, and of those which the ingenuity of the chemist is daily discovering, will enlarge the sphere of their practical applications. The caprylethers lately discovered by Bouris are remarkable for their aromatic smells (the acetate of capryloxide is possessed of the most intense and pleasant smell,) and they promise a large harvest to the manufacturers of perfumes.—Annalen der Chemie.—In An. of Pharmacy.