Chapter XV: Section 3: This Act shall not take effect until the first day of July, (12)

Whatever certain authors may have said on the subject, it is possible to discover in a suspected liquid all the alkaloids, in whatever state they may be. I am quite convinced that every Chemist who has kept up his knowledge as to analysis, will not only succeed in detecting their presence, but even in determining the nature of that which he has discovered, provided that the alkaloid in question is one of that class of bodies, the properties of which have been suitably studied. Thus he will be able to discover conia, nicotine, aniline, picoline, petinine, morphine, codeine, narcotine, strychnine, brucine, veratrine, colchicine, delphine, emetine, solanine, aconitine, atropine, hyoscyamine. I do not pretend to say that the chemical study of all these alkaloids has been sufficiently well made to enable the experimenter who detects one of them to know it immediately, and affirm that it is such an alkaloid, and not such another. Nevertheless, in those even which he cannot positively determine or specify, he may be able to say that it belongs to such a family of vegetables—the Solanaceæ, for example. In a case of poisoning by such agents, even this will be of much importance. The method which I now propose for detecting the alkaloids in suspected matters, is nearly the same as that employed for extracting those bodies from the vegetables which contain them. The only difference consists in the manner of setting them free, and of presenting them to the action of solvents. We know that the alkaloids form acid salts, which are equally soluble in water and alcohol; we know also that a solution of these acid salts can be decomposed so that the base set at liberty remains either momentarily or permanently in solution in the liquid. _I have observed that all the solid and fixed alkaloids above enumerated, when maintained in a free state_ {344} _and in solution in a liquid, can be taken up by ether when this solvent is in sufficient quantity._ Thus, to extract an alkaloid from a suspected substance, the only problem to resolve consists in separating, by the aid of simple means, the foreign matters, and then to find a base which, in rendering the alkaloid free, retains it in solution, in order that the ether may extract it from the liquid. Successive treatment by water and alcohol of different degrees of concentration, suffices for separating the foreign matters, and obtaining in a small bulk a solution in which the alkaloid can be found. The bicarbonates of potash or soda, or these alkalies in a caustic state, are convenient bases for setting the alkaloids at liberty, at the same time keeping them wholly in solution, especially if the alkaloids have been combined with an excess of tartaric or of oxalic acid.

To separate foreign substances, animal or otherwise, from the suspected matters, recourse is commonly had to the tribasic acetate of lead, and precipitating the lead afterwards by a current of sulphuretted hydrogen. As I have several times witnessed, this procedure has many and very serious inconveniences. In the first place, the tribasic acetate of lead, even when used in large excess, comes far short of precipitating all the foreign matters; secondly, the sulphuretted hydrogen, which is used to precipitate the lead, remains in combination with certain organic matters which undergo great changes by the action of the air and of even a moderate heat; so that animal liquids which have been precipitated by the tribasic acetate of lead, and from which the lead has been separated afterwards by hydrosulphuric acid, color rapidly on exposure to the air, and exhale at the same time a putrid odor, which adheres firmly to the matters which we extract afterwards from these liquids. The use of a salt of lead presents another inconvenience, viz.: the introduction of foreign metals into the suspected matters, so that that portion of the suspected substance is rendered unfit for testing for mineral substances. The successive and combined use of water and alcohol at different states of concentration, {345} permits us to search for mineral substances, whatever be their nature, so that in this way nothing is compromised, which is of immense advantage when the analyst does not know what poison he is to look for.

It is hardly necessary to say, that in medico-legal researches for the alkaloids, we ought never to use animal charcoal for decolorizing the liquids, because we may lose all the alkaloid in the suspected matters. It is generally known that animal charcoal absorbs these substances at the same time that it fixes the coloring and odoriferous matters.

[This is no doubt true; we must not use animal charcoal to decolorize, and then look for the alkaloid in the _liquid_, but we may use it, at least in the case of strychnia and some of the non-volatile alkaloids, to separate them, and then we look for them _in the charcoal_. See notice of Graham and Hofmann’s Process for Detecting Strychnia: _Monthly Journal_, Aug., 1852, p. 140; _Pharmaceutical Journal_, vol. xi., p. 504, May, 1852.]

The above observations do not proceed from speculative ideas only, but are the result of a pretty long series of experiments which I have several times employed for discovering these organic alkaloids. To put in practice the principles which I have thus explained, the following is the method in which I propose to set about such an analysis:—I suppose that we wish to look for an alkaloid in the contents of the stomach or intestines; we commence by adding to these matters twice their weight of pure and very strong alcohol;[26] we add afterwards, according to the quantity and nature of the suspected matter, from ten to thirty grains of tartaric or oxalic acid—in preference tartaric; we introduce the mixture into a flask, and heat it to 160° or 170° Fahrenheit. After it has completely cooled it is to be filtered, the insoluble residue washed with strong alcohol, and the {346} filtered liquid evaporated in vacuo. If the operator has not an air-pump, the liquid is to be exposed to a strong current of air at a temperature of not more than 90° Fahrenheit. If, after the volatilization of the alcohol, the residue contains fatty or other insoluble matters, the liquid is to be filtered a second time, and then the filtrate and washings of the filter evaporated in the air-pump till nearly dry. If we have no air pump, it is to be placed under a bell-jar over a vessel containing concentrated sulphuric acid. We are then to treat the residue with cold anhydrous alcohol, taking care to exhaust the substance thoroughly; we evaporate the alcohol in the open air at the ordinary temperature, or still better, in vacuo; we now dissolve the acid residue in the smallest possible quantity of water, and introduce the solution into a small test-tube, and add little by little pure powdered bicarbonate of soda or potash, till a fresh quantity produces no further effervescence of carbonic acid. We then agitate the whole with four or five times its bulk of pure ether, and leave it to settle. When the ether swimming on the top is perfectly clear, then decant some of it into a capsule, and leave it in _a very dry place_ to spontaneous evaporation.

[26] When we wish to look for an alkaloid in the tissue of an organ, as the liver, heart, or lungs, we must first divide the organ into very small fragments, moisten the mass with pure strong alcohol, then express strongly, and by further treatment with alcohol exhaust the tissue of everything soluble. The liquid so obtained, is to be treated in the same way as a mixture of suspected matter and alcohol.

Now, two orders of things may present themselves; either the alkaloid contained in the suspected matter is liquid and volatile, or solid and fixed. I shall now consider these two hypotheses.

EXAMINATION FOR A LIQUID AND VOLATILE ALKALI.

We suppose there exists a liquid and volatile alkaloid. In such a case, by the evaporation of the ether, there remains in the inside of the capsule some small liquid striæ which fall to the bottom of the vessel. In this case, under the influence of the heat of the hand, the contents of the capsule exhale an odor more or less disagreeable, which becomes, according to the nature of the alkaloid, more or less pungent, suffocating, irritant; it presents, in short, a smell like that of a volatile alkali masked by an animal odor. If we discover any traces of the presence of a volatile alkaloid, we add then to the contents {347} of the vessel, from which we have decanted a small quantity of ether, one or two fluid drachms of a strong solution of caustic potash or soda, and agitate the mixture. After a sufficient time, we draw off the ether into a test-tube; we exhaust the mixture by two or three treatments with ether, and unite all the ethereal fluids. We pour afterwards into this ether, holding the alkaloid in solution, one or two drachms of water, acidulated with a fifth part of its weight of pure sulphuric acid, agitate it for some time, leave it to settle, pour off the ether swimming on the top, and wash the acid liquid at the bottom with a new quantity of ether. As the sulphates of ammonia, of nicotine, aniline, quinoleine, picoline, and petinine, are entirely insoluble in ether, the water acidulated with sulphuric acid contains the alkaloid in a small bulk, and in the state of a pure sulphate; but as the sulphate of conia is soluble in ether, the ether may contain a small quantity of this alkali, but the greater part remains in the acidulated watery solution. The ether, on the other hand, retains all the animal matters which it has taken from the alkaline solutions. If it on spontaneous evaporation leaves a small quantity of a feebly-colored yellowish residue, of a repulsive animal odor, mixed with a certain quantity of sulphate of conine, this alkaloid exists in the suspected matter under analysis. To extract the alkaloid from the solution of the acid sulphate, we add to the latter an aqueous and concentrated solution of potash or caustic soda, we agitate and exhaust the mixture with pure ether; the ether dissolves ammonia, and the alkaloid is now free. We expose the ethereal solution at the lowest possible temperature to spontaneous evaporation; almost all the ammonia volatilizes with the ether, whilst the alkaloid remains as residue. To eliminate the last traces of ammonia, we place for a few minutes the vessel containing the alkaloid in a vacuum over sulphuric acid, and obtain the organic alkaloid with the chemical and physical characters which belong to it, and which it is now the Chemist’s duty to determine positively.

I applied, on the 3d March, 1851, the process which I have {348} described, to the detection of nicotine in the blood from the heart of a dog poisoned by two cubic centimetres [0.78 C.I.] of nicotine introduced into the œsophagus, and I was able in a most positive manner to determine the presence of nicotine in the blood. I was able to determine its physical characters, its odor, taste, and alkalinity. I succeeded in obtaining the chloroplatinate of the base perfectly crystallized in quadrilateral rhomboidal prisms of a rather dark yellow color, and to ascertain their insolubility in alcohol and ether.

I have applied the same process for the detection of conia in a very old tincture of hemlock, which my friend and colleague M. de Hemptinne was so kind as to put at my disposal; and I was equally successful in extracting from the liquid colorless conia, presenting all the physical and chemical properties of this alkali. I was also able to prove that the ether which holds conia in solution, carries off a notable portion of this alkaloid when the solvent is exposed to spontaneous evaporation.

EXAMINATION FOR A SOLID AND FIXED ALKALOID.

Let us now suppose that the alkali is solid and fixed; in that case, according to the nature of the alkali, it may happen that the evaporation of the ether resulting from the treatment of the acid matter, to which we have added bicarbonate of soda, may leave or not a residue, containing an alkaloid. If it does, we add a solution of caustic potash or soda to the liquid, and agitate it briskly with ether. This dissolves the vegetable alkaloid, now free and remaining in the solution of potash or soda. In either case, we exhaust the matter with ether. Whatever be the agent which has set the alkaloid free, whether it be the bicarbonate of soda or potash, or caustic soda or potash, it remains, by the evaporation of the ether, on the side of the capsule as a solid body, but more commonly a colorless milky liquid, holding solid matters in suspension. The odor of the substance is animal, disagreeable, but not pungent. It turns litmus paper permanently blue.

When we thus discover a solid alkaloid, the first thing to do is to try and obtain it in a crystalline state, so as to be able to {349} determine its form. Put some drops of alcohol in the capsule which contains the alkaloid, and leave the solution to spontaneous evaporation. It is, however, very rare that the alkaloid obtained by the above process is pure enough to crystallize. Almost always it is soiled by foreign matters. To isolate these substances, some drops of water, feebly acidulated with sulphuric acid, are poured into the capsule, and then moved over its surface, so as to bring it in contact with the matter in the capsule. Generally we observe that the acid water does not moisten the sides of the vessel. The matter which is contained in it separates into two parts, one formed of greasy matter, which remains adherent to the sides—the other alkaline, which dissolves and forms an acid sulphate. We cautiously decant the acid liquid, which ought to be limpid and colorless, if the process has been well executed; the capsule is well washed with some drops of acidulated water, added to the first liquid, and the whole is evaporated to three-fourths in vacuo, or under a bell-jar over sulphuric acid. We put into the residue a very concentrated solution of pure carbonate of potash, and treat the whole liquid with absolute alcohol. This dissolves the alkaloid, while it leaves untouched the sulphate of potash and excess of carbonate of potash. The evaporation of the alcoholic solution gives us the alkaloid in crystals.

It is now the Chemist’s business to determine its properties, to be able to prove its individuality. I have applied the principles which I have just expounded to the detection of morphine, iodine, strychnine, brucine, veratrine, emetine, colchicine, aconitine, atropine, hyoscyamine—and I have succeeded in isolating, without the least difficulty, these different alkalies, previously mixed with foreign matters.

I have thus been able to extract, by this process, morphine from opium, strychnine and brucine from nux vomica, veratrine from extract of veratram, emetine from extract of ipecacuanha, colchicine from tincture of colchicum, aconitine from an aqueous extract of aconite, hyoscyamine from a very old extract of henbane, and atropine from an equally old tincture of {350} belladonna. Thus it is in all confidence that I submit this process to the consideration of Chemists who undertake medico-legal researches.—_Bulletin de l’ Académie Royale de Médecine de Belgique_, tom. vi., No. 2; _and Edinburgh Monthly Journal of Medical Science_.

VARIA—EDITORIAL.

OINTMENT OF STAVESACRE IN ITCH.—It has long been known that the itch is caused by the attack of a minute insect, the acarus scabiei, the male of which has only been lately detected, by the microscope. The ordinary sulphur ointment, though successful after repeated applications, in destroying the insect, often causes a good deal of irritation of the skin, and leaves the patient with an eruption as troublesome if not as permanent as the itch itself. M. Bourguignon, a French physician, finds that the infusion of the seeds of the stavesacre, (Delphinium Staphisagria) or a solution of the extract, not only speedily kills the insects and destroys their eggs, but that it has no irritating influence whatever upon the skin itself. He afterwards adopted an ointment, prepared by digesting over a vapor bath, for twenty-four hours, three parts of stavesacre seeds in five parts of lard, and straining the product while still liquid. He found that friction with this ointment cured the patient in four days, while seven days were required when sulphur ointment was used.

POISONOUS HONEY.—The family of one of our most respectable wholesale druggists has lately suffered severely from symptoms of poisoning, caused by some honey which they had eaten. The family of one of his neighbors likewise, to whom, induced by its particularly fine appearance, he had sent some of the honey, were affected in a similar manner. The number of those who partook of the suspected article, all of whom were affected, though not to the same degree, renders it certain that the symptoms were not caused by any idiosyncracy, but were produced by some poisonous principle, probably derived from some narcotico-acrid plant on which the bees had fed.

On eating it there was an unpleasant sense of pricking and burning in the throat, nausea, and a burning sensation throughout the whole system, together with an immediate effect upon vision, approaching to blindness. Several of those who {351} ate of the honey vomited violently and were in great distress. One was rendered entirely blind and insensible, and it was feared for some time might not recover. In the other cases the effect passed off in some ten or twelve hours. In one case a single drop of the honey, taken on the end of the finger from the box where it had leaked through a crevice, had such an effect on the sight that the person could not see to read a newspaper, but it passed off within an hour.

“We are not aware,” continues our informant, “of any poisonous plants in the vicinity where the honey was made, except what is called kill-calf, (Andromeda Mariana) which is found in abundance on Hempstead Plains, at a distance of about a mile.”

If, as is supposed, the poison was derived from some plant in which the bees had fed, it must have been elaborated or concentrated in the economy of the insect, or been the product of some reaction of the honey itself upon the poisonous principle, since no poisonous vegetable is known which would produce such effects, in such minute quantity.

NEW REMEDIES.—Dr. J. Y. Simpson, of Edinburg, the discoverer of the anaesthetic properties of Chloroform, has lately been experimenting on the physiological and therapeutical properties of a varitey of substances which have not previously been used in medicine. He finds that the alkaloid furfurine in poisonous doses, produces upon animals many of the symptoms of poisoning by quinine, and that in smaller doses on the human subject it acts as a tonic, if not an anti-periodic. He has likewise used nickel, generally in the form of sulphate, and finds that it is exceedingly analagous in its therapeutic effects to the salts of iron. In one instance, however, a case of severe periodic headache, it proved completely successful, after iron with quinine, and a great many other remedies had been tried in vain.

THE CONVENTION.—The _event_ for Pharmaceutists in the past month, was the Meeting of the Convention at Philadelphia. The number present was smaller than could have been wished, yet great as could reasonably have been anticipated. Eight states were represented, including Mr. Bache, of San Francisco, California, and there were delegates present from five Colleges. We have devoted, perhaps, an undue portion of our space to a partial record of its proceedings. Though on particular points there were differences of opinion, yet on the whole the meetings were characterized by great unanimity of sentiment, as well as cordiality of feeling. Our great hope for the Convention is, that it will form a bond of union among the scattered and divided members of the profession in the United States; that it will tend to bring them into one great body, united by common interests and common pursuits, that it will tend to soften commercial jealousies between individuals, as well as between states and cities; that it will enable the profession when united, to exercise its rightful and legitimate influence upon {352} public opinion; that in the profession itself it will promote a more extended course of education, a higher standard of attainment and nobler principles of conduct. These are great aims and worthy of strenuous efforts, and it is to be hoped that no personal or sectional jealousies may be permitted to stand in the way of their attainment. The Convention has made a good beginning, “Esto perpetua.”

COLLEGE OF PHARMACY OF THE CITY OF NEW YORK.

The regular Winter Course of Lectures in this Institution, will commence on Monday, 1st instant, at 7 o’clock, P. M., and be continued four months, on Monday, Wednesday and Friday evenings of each week, at the College Rooms.

On Materia Medica and Pharmacy, from 7 to 8 o’clock, by Prof. B.W. MCCREADY, M.D.

On Chemistry, from 8 to 9 o’clock, by Professor R. O. DOREMUS, M.D.

On Botany, by Professor I. F. HOLTON, of which further notice will be given.

The Chemical Lectures will comprise instruction in the Science as extensively connected with many of the useful and ornamental arts, rendering them of great advantage to the community at large as well as to the Apothecary.

In calling public attention to the present Course, the Trustees would more especially call upon the Medical Profession and Druggists and Apothecaries generally, to encourage them in carrying out, in the most effectual manner, the important design of providing, at a nominal expense, for a knowledge of Chemistry, Pharmacy, and the collateral Sciences, to our future Apothecaries, and to all others who will avail themselves of the facilities offered.

In urging these, the Trustees have no selfish ends to attain beyond the gratification of ministering to the public good in the elevation of their profession; they desire to see their efforts appreciated and sustained by full classes, and would earnestly ask of their brethren to make sufficient sacrifice of time and convenience to enable their Assistants and Pupils to profit by the opportunity offered for their instruction. The advantages will recur directly to the employer in the improved capacity and usefulness of his Assistants.

The Trustees solicit the influence of the Medical Profession to aid them in cultivating a desire to improve this important Auxilliary Department of the Profession, as the successful treatment of disease is greatly dependent on the integrity and intelligence of the apothecary.

Tickets for the Course on Chemistry, at $7, and on Materia Medica and Pharmacy, at $7, may be procured from

MR. GEORGE D. COGGESHALL, No. 809 BROADWAY. MR. J. S. ASPINWALL, No. 86 WILLIAM STREET. DR. W. J. OLLIFFE, No. 6 BOWERY.

AND AT THE COLLEGE ROOMS, No. 511 BROADWAY.

October, 1852.

ERRATUM.—In the October No. on page 294, twentieth line from the top, for _manifestations_, read _modifications_.

{353}

NEW YORK

JOURNAL OF PHARMACY.

DECEMBER, 1852.

ON THE PRESERVATION OF IODIDE OF IRON.

BY HENRY WURTZ.

There can be no doubt that imperfections exist in many of the methods at present in use for the preservation of various articles of the materia medica. Wherever the fault may be in these cases, the evil is generally shared between the physicians and the patients, much the larger share of course, falling to the latter. The _iodide of iron_ is one of these articles, and it will appear probable from the sequel that, in a multitude of cases, this remedy is administered to the patient in quantities which are inconstant and much too small to produce the effect contemplated by the physician in his prescription.

One method, extensively employed, of preserving iodide of iron, for use in medicine, is in the form of an aqueous solution in which a coil of iron wire is kept immersed. This method is given by Pereira,[27] as proposed by Hemingway. Pereira also remarks in another place that “it is important to know, that by keeping a coil of iron wire in a solution of the protiodide, as suggested by Mr. Squire, no free iodine or sesquiodide of iron is formed although the liquid may be fully exposed to air and light; sesquioxide of iron is formed, but if the solution be filtered it is found to contain protiodide only.”

[27] Materia Medica, 3rd Am. Ed. 1, 745.

In a paper previously published in this journal, I have remarked with reference to this matter, that I should strongly {354} suspect in this case a formation of a subiodide of iron and consequent abstraction of iodine from the solution.[28] Since that time I have been enabled to confirm this supposition by experiment. Pieces of iron wire placed in contact with a colorless solution of iodide of iron caused, in the course of a few hours, the deposition of a precipitate, which had a dark orange color quite distinct from the dark brown color of hydrated sesquioxide of iron precipitated from a solution of the protochloride of iron by metallic iron. This precipitate, being washed with distilled water until the washings gave no indication of the presence of _iron_, was still found to contain much iodine. No quantitative analysis of the precipitate, however, was attempted, for it was found that the washings which no longer contained a trace of iron still gave with nitric acid and starch, a strong iodine reaction, thus indicating that the subiodide of iron upon the filter, whatever its composition, was decomposed by the action of water and oxygen as soon as the neutral iodide of iron was washed out. This is probably the reason why previous observers have mistaken this precipitate for pure sesquioxide of iron, having continued washing the precipitate until the washing no longer gave an _iodine_ reaction, instead of an _iron_ reaction as in the plan adopted by me, and consequently until all the subiodide of iron was decomposed and nothing but sesquioxide of iron was actually left upon the filter.

[28] New-York Journal of Pharmacy, August, 1852.

The washings, however, after the removal of the iodide of iron, gave no iodine reaction with starch until after the addition of nitric acid; iodine, therefore, could only have been present in the form of hydriodic acid and the reaction by which the unknown subiodide of iron was decomposed may be represented as follows:—2 Fe I^{1}‗{x} + ^{1}‗{x}H O + (3−^{1}‗{x})O = Fe ^{2}O^{3} + ^{1}‗{x}HI.

Since the above experiments were made, I have found that I have, after all, merely been in a measure confirming an observation of the illustrious Berzelius. _Gmelin’s Handbuch_ under the head of _Einfachiodeisen_, has the following, “Nach Berzelius ist das braune Pulver welches sich beim Aussetzen des {355} wässrigen Einfachiodeisens an die Luft absetzt, nicht reines Eisenoxyd, sondern ein basisches salz.”[29]

It appears, therefore, that the method of preserving iodide of iron in solution, in contact with metallic iron is perfectly fallacious. This remedy, if preserved in solution at all, should be kept in bottles hermetically closed.

[29] According to Berzelius, the brown powder, which is deposited upon exposure of aqueous protiodide of iron to the air, is not pure sesquioxide of iron, but a basic salt.

OBSERVATIONS ON THE VOLATILITY AND SOLUBILITY OF CANTHARDIN IN VIEW OF THE MOST ELEGIBLE PHARMACEUTICAL TREATMENT OF SPANISH FLIES.

BY WILLIAM PROCTER, JR.

Cantharides have been used in Pharmacy since the days of Hippocrates. It was not till 1810, however, that the principle giving them activity was isolated by Robiquet (Annal. de Chimie lxxvi. 302,) and subsequently named _Cantharidin_ by Dr. Thomas Thompson. Since then various experimenters have been engaged in the chemical investigation of these flies, and in the more recent treatises they are stated to consist of _cantharidin_, _yellow fixed oil_, _green fixed oil_, _a yellow viscous substance_, _a black matter_, _ozmazome_, _uric acid_, _acetic acid_, _phosphoric acid_, and the _phosphate of lime and magnesia_. It is proverbial among apothecaries and physicians, that the pharmaceutical preparations designed to produce vesication, vary very much in their power as prepared by different individuals, and from different samples of cantharides by the same recipes. Is this variableness of power due to the inequality of strength of the commercial drug? or, are we to attribute it to the treatment employed by the apothecary? The real importance of these queries demands an answer. To proceed {356} properly, the investigator should examine cantharidin in a pure state, ascertain how far the statements of writers are correct, then by a series of analyses, quantitative as regards that principle, determine whether its proportion varies, and to what extent, in different specimens of cantharides of fair quality; and finally to test the preparations derived from the same samples and see how far they correspond with the inferences drawn from the ascertained properties and proportion of the active principle. I have at present undertaken to resolve but a part of these queries—yet by far the most important ones—as will be seen.

Cantharidin is a white, neutral substance, of which the formula according to Regnault is C‗{10}H O‗{4}. Gmelin considers it of the nature of a solid volatile oil. As usually seen it has the form of minute flatted four-sided prisms (_c_,) much broken up, so as to appear like scales. When deposited from an ethereal solution of cantharides by slow evaporation, or from its solution in hot acetic acid by cooling, it assumes the form of flattened oblique four-sided prisms with dihedral summits, derived from the rectangular prism by the bevelment of its edges (see fig. _a_ and _b_ from _c_.) The crystals by slow sublimation are four-sided rectangular prisms of great brilliance and sometimes iridescent, _c_ and _d_.

SOLUBILITY.—Pure cantharidin is insoluble in water, hot or cold. It is slightly soluble in cold alcohol, readily so when hot. Ether dissolves it to a greater extent, yet much more easily hot than cold. Chloroform is its best solvent, cold or hot, as shown in a former essay (Am. Jour. Pharm. vol. xxiii. 124,) and will remove it from the aqueous infusion of the flies. Acetic ether dissolves cantharidin, especially when hot, but does not retain much on cooling. When one part of cantharides is mixed with 20 parts of olive oil and heated to 250° Fahr. it is completely dissolved. As the solution cools, the cantharidin rapidly separates in shining needles in such quantity as {357} at first to give the oil a pulpy consistence. The clear cold oil retains sufficient to act as an efficient rubefacient but not as an epispastic. One part of cantharidin requires 70 parts of oil of turpentine to dissolve it at the boiling temperature, the greater part separating, as the solution cools, in long asbestos-like needles. A piece of paper saturated with the cold solution and applied to the skin under adhesive plaster did not vesicate. Acetone (from the distillation of acetate of lime) dissolves cantharidin with great readiness and ranks next to chloroform in this regard. The solution deposits the substance in crystals by evaporation. The commercial methylic alcohol or wood naphtha also dissolves cantharidin, but to a much less extent than acetone. When acetic acid sp. gr. 1.41 (U. S. P.) is added to cantharidin, it but slightly acts on it in the cold; heat much increases its solvent power, which is lost on cooling and the substance deposited by standing, though not immediately. One part of cantharidin was mixed with 40 parts of _crystallizable_ acetic acid and agitated together during five hours, but a small percentage was dissolved; but on applying heat the crystals were dissolved quickly. On standing, nearly all of the cantharidin was slowly deposited in regular crystals. To ascertain whether, as has been asserted,[30] a combination was effected, and an _acetate_ of cantharidin produced, an acetic solution of cantharidin was evaporated to dryness and the crystals mixed with strong sulphuric acid and heated till dissolved, while the nose was held near, without the slightest evidence of acetic odor; one twentieth of a grain of acetate of potassa was then added, which instantly evolved the well marked smell of acetic acid. Formic acid dissolves but a trace of cantharidin, cold or hot; and muriatic acid sp. gr. 1.18 hardly can be said to act on it in the cold, but when boiling a minute portion is taken up. The same is true of phosphoric acid dissolved in five parts water. Sulphuric acid sp. gr. 1.840, when heated readily dissolves pure cantharidin without being discolored, {358} and deposits it in crystals unchanged by cooling. Hot nitric acid sp. gr. 1.38, dissolves cantharidin readily, and deposits the greater part of it on cooling in brilliant crystals, unchanged. A concentrated solution of ammonia slowly dissolves cantharidin to a small extent, and yields it up on evaporation in crystals. Solutions of pottassa and of soda also dissolve this principle.

[30] New York Jour. Pharm. vol. 1. p. 72.

ITS VOLATILITY.—About ten grains of pure and perfectly dry cantharidin was spread on the pan of an Oertling’s balance, (sensitive to 1-150th of a grain,) and the equilibrium carefully adjusted with platina weights. After exposure for a week to the action of the air, a vessel of lime being present to keep the air dry, no change in the adjustment had occurred. To further test the volatility of cantharidin, a portion of it was put at the bottom of a dry test tube, through a paper funnel so as not to soil the sides, which was then fixed so as to dip half an inch in a mercurial bath having a thermometer suspended in it. It lost nothing appreciable after being kept at 212° F. for half an hour, no sublimate being visible with a lens. At 220° F. no visible effect was produced. Kept at 250° F. for twenty minutes, a very slow sublimation commenced. At 300° F. the vaporization was but slightly increased. The heat was then raised to 360° F., when the sublimation became more decided, yet still slow. Between 402° F. and 410° F. it fused, and rapidly sublimed at a few degrees higher. Cantharidin at this temperature volatilizes with great ease and condenses in beautiful well defined crystals like salicylic acid.

The specific gravity of cantharidin is considerable, as it sinks in nitric acid sp. gr. 1.38; it is exceedingly acrid; its powder applied to the skin with a little oil, produces speedy vesication, and taken internally it is an irritant poison of the most virulent kind.

Such are some of the more prominent characters of this remarkable substance, which exhibits a permanence and want of affinity extraordinary in an animal principle. Let us now see how far experiments with cantharidin as it exists in the flies in substance, correspond with its behaviour in an isolated state. {359}

1st. Is cantharidin, as it exists in Spanish flies, volatile at common temperatures, or at the temperature usually employed in making the cerate; and if so to what extent?

_a._ Six hundred grains of powdered cantharides were put into a quart flask, a pint of water poured on, and macerated two hours. The flask was then adapted to a glass tubulated receiver by means of a long glass tube, the joints made tight, and the tube refrigerated throughout its length by a current of cool water, the receiver itself being surrounded by water. A sand-bath heat was then applied and the materials in the flask kept boiling during several hours, until half a pint liquid had distilled. The product in the receiver was opalescent, with white particles floating through it, and had a strong odor of spanish flies. It was decanted into a bottle, and agitated repeatedly with half an ounce of chloroform, which dissolved the particles and removed the opalescence. The chloroform, when separated with a funnel, and evaporated spontaneously, yielded a colorless semi-crystalline residue, having a waxy consistence and a strong odor different from that of the flies. It fused at 120° Fahr., was volatile _per se_, but was partially decomposed and condensed in drops which subsequently solidified. This substance is soluble in alcohol, ether and chloroform, is decomposed and dissolved by sulphuric acid, produces _no signs of vesication after forty-eight hours’ contact with the skin_ under adhesive plaster, and is most probably the same volatile principle that has been noticed by Orfila.

The long glass tube was then examined for a sublimate, by rinsing it thoroughly with chloroform, which, on evaporation, afforded more of the same substance obtained from the distilled water, and like it did not produce vesication.

This experiment shows conclusively that cantharidin _does not volatilize to an appreciable extent with water evaporating from cantharides_.

_b._ More water was added to the residue in the flask, again boiled for fifteen minutes and thrown on a displacing filter, and water added to the solid residue, after the decoction had {360} ceased to pass, until the absorbed liquid was displaced. The decoction was much less odorous than the distilled water, and had a deep reddish-brown color. Half of this was agitated repeatedly with chloroform. The latter decanted and evaporated yielded a crop of crystals intermixed with some coloring matter. A part of these heated in a tube over a lamp, gave immediately the brilliant crystaline sublimate of cantharidin well marked; another portion applied to the skin produced vesication in a few hours.

The other half of the decoction was evaporated to a soft extract by direct heat. This produced speedy and deep vesication, more effectual than that of pure cantharidin, as in the extract that principle was in a soluble state by virtue of the yellow matter of the flies.

_c._ The residual flies were then dried carefully and exhausted with ether, which assumed a deep green color. A green semi-fluid fatty oil was obtained by evaporation, from which a fluid yellow oil separated by standing, which produced a tardy vesication, not comparable with the aqueous extract.

_d._ One hundred grains of flies in powder were introduced into a test tube so as not to soil the sides. This was then kept at the temperature of 212° F. during six hours, by causing it to dip into a vessel of boiling water through a tin plate. The hygrometric water was removed as it condensed above. At the end of the experiment a minute deposit of microscopic crystals less than one thirtieth of a grain, was observed above the flies on the side of the tube.

_e._ Two hundred grains of flies were introduced into a two ounce retort, which they half filled, adapted to a two ounce receiver, and this again connected with a third vessel. The retort heated by a mercurial bath, was kept at 225° F., for two hours, without any product except a little odorous hygrometric water. The heat was then raised to 412° F., when a colorless oily matter flowed slowly into the receiver, mixed with water, whilst a crystalline matter mixed with oil collected in the neck. This crystalline matter mixed with the oil produced {361} vesication when applied to the skin. The heat was now rapidly increased so as to produce brown vapors, from which was condensed a dark colored empyreumatic oil, abundant crystals of an ammonical salt collected in the tubes and on the sides of the receiver, whilst the aqueous liquor in the receiver was strongly ammonical. Neither the dark oil nor the crystals produced vesication, the high temperature having probably decomposed the cantharidin.

From these experiments it must be admitted that cantharidin is less volatile than has been asserted. The effect produced on the eye of the pupil of Robiquet who was watching the crystallization of cantharidin during the evaporation of an ethereal solution, may be accounted for by the mechanical action of the dense ethereal vapor escaping near his eye, as he watched the process with a lens, carrying off some particles of cantharidin; and the readiness with which this principle may be brought mechanically in contact with the skin of the face, during a series of experiments, by want of care, will easily account for the occasional testimony of writers in favor of its volatility at low temperatures based on that kind of evidence. During the whole of the experiments detailed in this paper, the author has not experienced any inconvenience to his eyes or face except in two instances, once when decomposing cantharides by destructive distillation, during which some of the vapors escaped near his person, and again where a small capsule containing aqueous extract of cantharides was accidentally exposed to high temperature over a lamp so as to partially decompose it; he suffered slight pain for a few hours in the conjunctiva of both eyes.

It must also be admitted that the heat ordinarily employed in making the blistering cerate of the United States Pharmacopœia, does not injure the preparation by volatilizing the cantharidin, and that the recommendation to digest the flies in the melted vehicle on a water bath is not only not injurious, but decidedly advantageous, as it increases, many fold, the solvent power of the fatty matter. {362}

2d. Having ascertained the solvent powers of olive oil, oil of turpentine and acetic acid, on pure cantharidin, the following experiments were made with those menstrua, and with water, on the flies in substance:

_a._ One hundred grains of powdered cantharides were mixed with two hundred grains of olive oil in a large test tube, which was corked, and the mixture heated in a boiling water bath during four hours, with occasional agitation. The contents of the tube were then poured into a small glass displacement apparatus, surrounded with water kept hot by a lamp, and the saturated oil gradually displaced, without cooling, by the addition of fresh portions of oil. The oily liquid thus obtained had a deep green color, smelled strongly of the flies, and when applied to the skin produced full vesication in about twelve hours contact. After standing twenty-four hours shining needles of cantharidin gradually separated, but not in quantity.

_b._ One hundred grains of powdered flies were mixed with two hundred grains of pure oil of turpentine in a closed tube, heated in a boiling water bath four hours, and displaced while hot as in the preceding experiment. The terebinthinate solution had a dull yellow color, and was perfectly transparent as it passed, but in a short time numerous minute stellated crystals commenced forming, which increased in quantity by standing. The saturated cold solution, separated from the crystals after standing twenty-four hours, did not blister when applied to the skin.

_c._ One hundred grains of powdered flies were digested in a close vessel, at the temperature of boiling water, in three hundred grains of acetic acid sp. gr. 1.041, for six hours, and then subjected to displacement in the hot filter above noticed. A dark reddish-brown transparent liquid passed, which had very little odor of flies, even when a portion was exposed until the acetic acid had nearly all evaporated. A portion of this liquid applied to the skin produced complete vesication in about ten hours. After standing a few hours, numerous minute {363} granular crystals were deposited, which gradually increased in amount and size.

These three experiments prove that hot fatty matter is a good solvent for cantharidin as it exists in the flies, and that it retains more on cooling than either turpentine or acetic acid. That hot oil of turpentine is a good solvent for extracting cantharidin, although it does not retain much on cooling, and that officinal acetic acid at the temperature of 212° F. will remove cantharidin readily from Spanish flies, but retains but a part on cooling.

_d._ Five hundred grains of recently powdered flies, contained in a flask, were boiled in a pint of water, for an hour, and the clear decoction decanted, the residue again treated with half a pint of water, so as to remove all matter soluble in that liquid. The decoctions were mixed, filtered, and evaporated carefully to dryness. The extract was exhausted by repeated treatment with boiling alcohol, which left a dark colored pulpy matter, very soluble in water, from which it is precipitated by subacetate of lead. The alcoholic solution was now evaporated to a syrup, and on cooling yielded a yellow extract like mass, interspersed with numerous minute four-sided prisms. By washing a portion with water, the yellow matter was removed, leaving the crystals white and pure. The aqueous washings yielded by evaporation a residue of crystals, and does not vesicate. When the alcoholic extract was treated with chloroform the crystals were dissolved, and the yellow matter left. On evaporating the chloroform solution the crystals were re-obtained with all the characters of cantharidin. The matter left by chloroform was now treated with water, in which it dissolved, except a trace of dark substance, and was again evaporated carefully. It afforded a yellow honey-like residue, thickly interspersed with crystals and strongly acid to litmus, without vesicating power.

A portion of the yellow matter separated from the alcoholic extract by water was boiled with some cantharidin, filtered and evaporated. The residue treated with chloroform afforded no {364} cantharidin; hence it would appear that although the yellow matter enables the cantharidin to dissolve in water and cold alcohol, when once separated its solvent power ceases.

Having now studied the effects of the ordinary solvents on cantharidin in a free state, and in the condition in which it exists in the insect, we are prepared to consider with some clearness, the pharmaceutical preparations of the Spanish fly, and their action as vesicants.

_a._ If 1-30th of a grain of pure cantharidin, in fine powder, be placed on the skin of the arm and covered with a piece of warmed adhesive plaster, active vesication occurs in eight hours, with pain. If the same quantity of cantharidin be put on the other arm, a small piece of paper be laid over it, and then a piece of adhesive plaster with a circular hole in it be applied, so as to hold on the paper, no vesication occurs in sixteen hours, the powder remaining dry. If then a large piece of plaster be put over the whole, at the end of eight hours more no blistering action will have taken place. If now a trace of olive oil be applied to the back of the paper covering the cantharidin, and the plaster replaced, speedy vesication will occur. These experiments prove that cantharidin must be in solution to have its vesicating action, and that oily matter is a proper medium.

_b._ When powdered flies are stirred into the ordinary vehicle of resin, wax, and lard, so as to chill it almost immediately as was formerly directed, but little of the cantharidin is dissolved by the fatty matter, and when applied to the skin the process of vesication is retarded. If, however, the cerate be kept fluid for a length of time, say for half an hour, by a water-bath or other regular heat, no loss of cantharidin occurs by the heat, the active principle is in a great measure dissolved by the fat, and every part is impregnated and active. In the foregoing experiments it has been shown that twenty parts of olive oil will dissolve one of cantharidin when hot. If we admit with Thierry that cantharides contain but four thousandths of their weight of cantharidin, the quantity contained in a {365} pound of cerate is about _eight_ grains, whilst the lard in the same weight of cerate is 1600 grains, or two hundred times the weight of that principle, not to speak of the influence of the wax and resin, which, in union, with the melted lard, act as solvents. Hence the whole of the cantharidin may be dissolved by the vehicle. Another advantage of employing a continued heat in digestion is the removal of the hygrometric water from the flies, which is the source of the mouldiness to which the cerate is prone in certain conditions.

In a former essay (Amer. Journ. Pharm., vol. xiii, p. 302,) I have advocated digestion in making this cerate, (a recommendation also made by Mr. Donovan, of Dublin, about the same time,) and also the use of a portion of the oil of turpentine to facilitate the solution of the cantharidin, but the foregoing experiments prove that fatty matter is quite as good, if not a better solvent alone than with turpentine.

_c._ It has been asserted long ago by Beaupoil, Robiquet and others, that water will perfectly extract the active matter from Spanish flies, which these experiments corroborate. Hence it is easy to understand how the condensed perspiration may facilitate the action of a blister, especially when, as was formerly much the case, its surface is coated with the dust of the flies, and the skin moistened.

It is also clear why the Unguentum Cantharidis of the United States Pharmacopœia is active although made with a decoction of flies, yet, in this preparation, care should be observed not to evaporate all the water, as on the existence of the aqueous extract in a soft state depends much of the efficiency of the preparation as an irritant dressing.

_d._ In the Linimentum Cantharidis, United States Pharm., in which an ounce of flies is digested in eight fluid ounces of oil of turpentine, the cantharidin is to be the menstruum as 1 to 1500, a proportion probably quite sufficient to retain it in solution. The importance of the officinal direction to digest is evident. It is quite doubtful whether this liniment, as made by the process of Dr. Joseph Hartshorne, one part of flies to {366} three parts of oil, will retain all the cantharidin after standing awhile.

_e._ The Acetum Cantharidis, (Lond. Ph.) made by macerating an ounce of flies in ten fluid ounces of acetic acid, 1.48, has been criticised by Mr. Redwood, (Pharm. Journal, Oct. 1841,) who arrived at the conclusion that it owed its vesicating power almost solely to the acid, he not being able to discover cantharidin in it. The inefficiency of _cold_ acetic acid as a solvent for _pure_ cantharidin has been proven by the above experiments, and its efficiency when hot equally shown. There can be little doubt that the London preparation would be much improved by _digesting_ the flies in the acid for an hour in a close glass vessel at the temperature of boiling water.

_f._ The _cantharidal collodion_ of M. Ilisch has been considerably used as a vesicant in this country. Ether being a good solvent for cantharidin readily keeps that principle in solution. When applied to the skin, the escape of the ether leaves a coating of ethereal extract of cantharides, admixed with collodion. This preparation sometimes fails from a deficiency of cantharidin, at other times from want of a sufficient body in the collodion excipient, and it has been found more advantageous to treat the cantharides with ether till exhausted, distill off the ether, and add the oily residue to collodion of the proper consistence. The addition of a little olive oil, and of Venice turpentine, as recommended by Mr. Rand, will give more activity to the preparation, especially if a piece of oiled silk or adhesive plaster be applied over the part.

_g._ Besides these, many other epispastic preparations are made in France and other countries. The acetic alcoholic extract of cantharides of Ferrari is made by digesting four parts of cantharides in sixteen parts of alcohol 36° B. mixed with one part of acetic acid 10° B. In the opinion of the author, the acetic acid tends to prevent the crystallization of the cantharidin, a statement rendered doubtful by the above experiments, as that principle separates in crystals from an acetic solution of cantharides. The alcohol dissolves the green oil {367} which gives to the extract a butyraceous consistence. This is undoubtedly an efficient preparation, and is used by spreading it on paper with a brush, and applying to the skin. Nearly all the French preparations direct digestion of from 2 to 6 hours, showing evidently that the experience of pharmaceutists is opposed to the opinion that cantharides is “a very volatile substance, even at common temperatures.”

The vesicating tafeta of the Codex, is that proposed by Messrs. Henry & Guibourt, and is made by fusing together one part of the ethereal extract of cantharides and two of wax, and spreading it on waxed paper or linen in the manner of adhesive plaster. This preparation is said to lose its efficiency by exposure to the air. How can this occur in view of the results which have been detailed above? admitting the fact, it is not probable that the change lies in the strong tendency of the cantharidin to separate in crystals? a change easily observable in the ethereal extract. This is the chief objection to some otherwise excellent preparations of cantharides for vesication, and it is far more probably the true explanation, than, that volatility should be the cause.