Accompanying “Syphilodol” advertising sent to physicians is a circular letter inviting the doctor to become a member in the “United States Bacteriological and Research Institute.” The “institute” seems to be a means of suggesting that the physician have bacteriologic, pathologic and serologic examinations made on behalf of his patients. In view of the fact that it is to the commercial interest of the French Medicinal Company to have as many users of “Syphilodol” as possible, it would be interesting to know what proportion of the Wassermann tests are reported negative.
Shorn of its mystery, Syphilodol the “synthetic chemical product of silver, arsenic and antimony” is essentially mercurous iodid—yellow iodid of mercury.
Details of Analysis
SYPHILODOL TABLETS
In France there has been on the market for some time a synthetic compound of silver, arsenic and antimony having the general structure of arsphenamin. Structurally, the formula as given by Bonard, Danyss and Tournier is (C12H12N2As2) 2AgBrSbO (H2SO4)2— dioxy═ diamino arsenobensolstibicosilver sulphate. As the advertising matter for “Syphilodol” referred to the synthetic compound of silver, antimony and arsenic, and also to its use in syphilis by Fournier, the above compound was first suspected. However, the general characteristics of syphilodol tablets, such as partial solubility in water, but not soluble in sodium hydroxid, sodium bicarbonate or acids, threw doubt on the hypothesis. When a small amount of the powdered tablets was treated with water, a yellow residue could be filtered off; the filtrate was pink, opalescent, which on standing gave a clear pink solution, and a small yellow precipitate. The residue, when allowed to remain in sulphuric acid solution (20 per cent.) over night became red; on boiling, the red precipitate with sulphuric acid, the precipitate volatilized and could be condensed in a watch glass. Adding a pinch of manganese dioxid to the hot sulphuric acid mixture caused an evolution of iodin fumes. A small amount of powdered syphilodol tablets was placed in the sunlight; they turned from yellow to black. All these reactions are typical of mercurous iodid—yellow iodid of mercury.
MERCURY, SILVER, ARSENIC, ANTIMONY
I. Mercury.—Two methods were used to determine the mercury: (a) 1.4535 gm. of powdered syphilodol was treated with 10 c.c. of a 50 per cent. sodium sulphid solution. The solution was then transferred with washings (about 20 c.c.) to a cathode cup, previously weighed with its contained mercury. The mercury compound was electrolyzed by a current of about 8 volts and 3 amperes, using a rotating anode. The solution (and some sulphur suspension) was removed by siphon, pouring in water until the amperage of the current was close to zero (U. S. P., IX, p. 587). The increased weight in mercury was 0.1612 gm.
II. To serve as a check on the foregoing method, mercury was also determined in the following method, which also allowed systematic tests for silver, antimony and arsenic. (b) 1.1023 gm. of the sample was placed in an Erlenmeyer flask, 50 c.c. of water, 50 c.c. of sodium hydroxid solution (10 per cent.) and 20 c.c. of formaldehyd solution, U. S. P., added. The solution was boiled for ten minutes and maintained at temperature of steam bath for two hours. (This reduces the mercury salt to mercury and any silver salt to silver; antimony would probably be likewise reduced.) The precipitated mercury was transferred by water, and concentrated nitric acid added. (The nitric acid solution is boiled to oxidize all mercurous nitrate to mercuric nitrate.) A small white precipitate was obtained at this point which seemed to be insoluble in aqua regia (calcium sulphate). The filtrate from this precipitate, which was washed well, was tested with one or two drops of dilute hydrochloric acid and a faint precipitate formed; this was filtered off through extra fine filter paper and washed repeatedly. The paper and precipitate was heated with potassium cyanid solution over night, filtered and the filtrate electrolyzed in a platinum dish. The increase in weight of the dish was 0.00018 gm., or 0.001 per cent. Into the platinum dish some nitric acid was poured, then diluted, and a drop of hydrochloric acid added. A turbidity was produced which cleared on the addition of excess of ammonium hydroxid solution (silver). The filtrate from the nitric acid treatment was electrolyzed, this time in a platinum dish, and the liquid carefully removed, washed carefully with redistilled alcohol and ether. The mercury, which could be seen easily by the naked eye, weighed 0.1200 gm., equivalent to 10.89 per cent. of mercury.
III. Arsenic and Antimony.—About 3 gm. of the powdered specimen was digested with sulphuric acid in a Kjeldahl flask. One-half portion (which was evaporated almost to dryness and treated with 5 c.c. of concentrated hydrochloric acid) was submitted to treatment with hydrogen sulphid, diluted, and saturated with hydrogen sulphid. The precipitate was treated in the usual manner of the group separation with warm ammonium sulphid solution. The filtrate from this treatment was acidulated with hydrochloric acid, the precipitate removed, and treated with concentrated hydrochloric acid. The substance insoluble in hydrochloric acid was treated with more concentrated hydrochloric acid and a crystal of potassium chlorate. The solution was tested after the Gutzeit method of the Pharmacopeia IX, for arsenic. A very small amount was indicated. The hydrogen sulphid test was not indicative. The solution which might contain the antimony was tested with hydrogen sulphid. In one case only was a slight orange coloration produced. No antimony was deposited on platinum foil in the presence of granulated zinc. These tests were run in triplicate.
Iodid.—Iodid was determined by the Carius method (a) 0.7412 gm. yielded 0.1112 gm. silver iodid, equivalent to 8.09 per cent.; (b) 0.5319 gm. yielded 0.0751 gm., equivalent to 7.80 per cent. The iodid and mercury were in proportions comparable to mercurous iodid.