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}