as early as 1809. Pereira, for example, in his Elements of Materia Medica and Therapeutics, fourth edition, 1854, vol. i, p. 856, states that arseniate of iron is "obtained by adding the arseniate of potash, soda, or of ammonia to a solution of protosulphate of iron," and has noted, with the subjoined reference, that "Mr. Carmichael used it externally in ulcerated cancer" (Carmichael : Essay on the Effects of Carbonate and other Preparations of Iron upon Cancer, pp. 50, 66, 341, 343 et seq., 1809).

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The Pharmacopée Universelle, par A. J. L. Jourdan, tome premier, Paris, 1828, p. 216, refers to the salt as follows: "Arséniate de Fer. Aucune pharmacopée n'indique la manière de préparer ce sel." It gives, however, a formula for the preparation of Pilules d'Arséniate de Fer," which appears to have been taken from the following work: Ratier (F.S.), Formulaire Pratique des Hôpitaux civils de Paris, third edition, Paris, 1827. The above-mentioned pills contained one-sixteenth of a grain each of iron arsenate, and the following indications were given for their use: "Conseillées, d'après les Anglais, dans les affections cancéreuses et les dartres ulcérées. Dose, une pilule par jour." A method for preparing the salt was given in L'Officine, par Dorvault, pharmacien, Paris, 1844, p. 154, as follows: "Arséniate de Fer.-S'obtient en décomposant une solution de sulfate de fer, par une autre d'arséniate de potasse : on recueille et on lave le précipité, qui est de l'arséniate de fer."

Iron arsenate was not included in the last editions of the London (1851), Edinburgh (1841), and Dublin (1850) Pharmacopoeias, and its first official recognition therefore appears to have been in the British Pharmacopoeia of 1864. Although the article was retained in all the subsequent revisions of the latter work, a comparison of the text clearly indicates that the subject has always been one of considerable perplexity to those who were entrusted with the compilation of the Pharmacopoeia, as well as to those who were expected to be guided by it. The divergencies with respect to the method of preparation and the requirements embodied in the quantitative tests are, in fact, quite remarkable, as may be seen by the following abstracts from the successive editions of the British Pharmacopoeia.

In the Pharmacopoeia of 1864 Ferri Arsenias was defined as Arseniate of Iron, 3FeO,AsO,, partially oxidated." It was prepared by the interaction of ferrous sulphate (9 parts) and sodium arseniate, dried at 300°F. (4 parts) with sodium acetate (3 parts); the latter salt having been used to obviate

any loss which otherwise would have been occasioned by the solvent action of free sulphuric acid. The solution of the compound in hydrochloric acid was stated to give "a copious lightblue precipitate with the ferrideyanide of potassium, and a still more abundant one of a deeper colour with the ferrocyanide of potassium." The volumetric test required the presence in the compound of such an amount of ferrous salt as would correspond to at least 1.428 per cent. Fe, or 3-791 per cent. Fe3(AsO4)2In the Pharmacopoeia of 1867 the definition of the compound and the method for its preparation were practically the same as in the previous edition. An important change was made, however, in the description of its character, since it was stated that its solution in hydrochloric acid "gives a copious lightblue precipitate with the yellow prussiate of potash, and a still more abundant one of a deeper colour with the red prussiate of potash." This indication of a predominating amount of ferrous salt in the compound likewise found expression in the quantitative test, which stated that it should require such an amount of volumetric solution of potassium bichromate for its oxidation as would correspond to at least 14.28 per cent. Fe, or 37-91 per cent. Fe(ASO4)2. As these figures are exactly ten times as great as those in the edition of 1864, one might attribute them to a typographical error were it not for the fact that in both cases they are obviously quite incorrect.1

In the Pharmacopoeia of 1885 Ferri Arsenias was defined as "arseniates of iron, with some oxide." In this edition the proportions of the salts directed to be used in its manufacture differed considerably from those of the earlier pharmacopoeias, and were as follows: Ferrous sulphate (20 parts), sodium arsenate, dried at 300°F. (15 parts), and sodium bicarbonate (4 parts); the latter salt having been adopted for the neutralization of the sulphuric acid produced by the reaction, in place of the sodium acetate previously employed. It will be seen from the above proportions that the amount of sodium arsenate, relative to that of ferrous sulphate em

1 W. H. Symons (Pharm. Journ., January 19, 1884, p. 562) has recorded that two samples of iron arsenate, examined by him, were found to contain 6.5 and 5:47 per cent. respectively of ferrous salt, whereas a preparation made by himself, according to the directions of the Pharmacopoeia, contained 27.2 per cent. of ferrous arsenate. The latter figure, although considerably below the pharmacopoeial requirement of the time, is still so high as to indicate some error in the determination. Compare also Nicholls (Year-Book of Pharmacy, 1903, p. 576).

ployed, is nearly 75 per cent. greater than in the two preceding editions. The qualitative test remained the same as in the Pharmacopoeia of 1867, indicating a predominance of ferrous salt, but a very great change was again made in the quantitative test, which required that the preparation should contain such an amount of ferrous salt as would correspond to at least 3-78 per cent. Fe, or 10-03 per cent. Fe, (AsO4)2.

In the Pharmacopoeia of 1898, which is the present official standard, a slight change was made in the definition of iron arsenate, as noted in the beginning of this paper. An alteration was also made in the wording of the qualitative test, which now reads as follows: " It affords the reactions characteristic of ferrous and ferric salts and of arsenates." The quantitative test requires the preparation to contain an amount of ferrous salt "corresponding to nearly 12 per cent. of hydrous or 10 per cent. of anhydrous, ferrous arsenate." The exact figures, as calculated from the stated amount of volumetric solution of potassium bichromate of the B.P. (1 c.c. = 0.00556 Fe), would be represented by 3.72 per cent. Fe, 9.89 per cent. Fe3(AsO4)2, or 12-28 per cent. Fe3(AsO4)2,6H2O, and are thus in practical agreement with the requirement of the Pharmacopoeia of 1885.

Preparations known as iron arsenate have also been recognized by the Pharmacopoeias of France, Italy, Spain, and Mexico,1 but the proportions of the salts directed to be employed in their manufacture differ materially in all of them, and, as might be expected, the resulting products differ appreciably in their composition.

The French Pharmacopoeia, edition of 1895, under the title of Arséniate Ferreux, recognizes a compound to which the formula FeHASO, is assigned, and which is directed to be prepared by mixing a solution of 50 grammes of crystallized sodium. arsenate with a solution of 10 grammes of crystallized ferrous sulphate. The resulting precipitate is of such a character that it cannot be washed either by decantation or on a filter, and can only be collected by forcible expression on a strainer. If the mixture be allowed to stand for a few hours, the precipitate becomes

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1 The statements in the U.S. Dispensatory, eighteenth edition, p. 605 that This is an official salt of the British Pharmacopoeia, which as yet is the only one that has adopted it," and in the National Standard Dispensatory, p. 617, that, besides the British and French, "no other pharmacopoeias recognize ferrous arsenate," are obviously not quite correct.

to a large extent redissolved. Only qualitative tests are given for the identity and purity of the product.

The Italian Pharmacopoeia of 1892, under the title of Arseniato Ferroso-Ferrico, recognizes a compound which is directed to be prepared by adding a solution of seven parts of crystallized sodium arsenate (Na2HASO4,8H2O) to a solution of six parts of crystallized ferrous sulphate, washing the resulting precipitate, and drying it at a temperature not exceeding 30°C. In addition to some tests for the identity and purity of the product, it is stated that 100 parts of it correspond to about 46 parts of arsenic acid, H3AsO4. Among the various pharmacopoeias which recognize iron arsenate, the Italian is the only one which prescribes any control respecting its arsenical content.

The Spanish Pharmacopoeia, seventh edition (1905), under the title of Arseniato de Hierro, recognizes a compound which is stated to be a ferroso-ferric arsenate. It is directed to be prepared by adding to a solution of 100 parts of crystallized ferrous sulphate a solution of 275 parts of crystallized sodium arsenate, until, after stirring and allowing the precipitate to subside, the clear supernatant liquid has an alkaline reaction.1 No specific tests are given for the presence of either iron or arsenic in the compound, nor is any requirement made respecting the amount which it should contain of these elements.

The Mexican Pharmacopoeia, second edition (1884), has adopted both an arsenite and an arsenate of iron, the latter bearing the official title of Arseniato de Fierro. This is directed to be prepared by mixing a solution of 24 parts of crystallized ferrous sulphate with a solution of 20 parts of potassium arsenate, KH2ASO4. No requirement is made respecting the amount of iron or arsenic to be contained in the product.

The variation in the proportions of the salts directed by the previously mentioned pharmacopoeias to be employed in the preparation of iron arsenate may be seen by the following table. For convenience of comparison the prescribed amounts of alkali arsenate are calculated into the corresponding amounts of anhydrous sodium arsenate, and uniformly with reference to 10 parts of crystallized ferrous sulphate.

1 We have observed that two-thirds of the prescribed amount of sodium arsenate is sufficient to impart to the liquid an alkaline reaction, but it has not been found practicable to wash the precipitate by decantation as directed.

The calculated amount of anhydrous sodium arsenate which would be required to react with ten parts of crystallized ferrous sulphate, for the production of a normal ferrous arsenate, is 4.5 parts, in accordance with the following essential factors of the equation:-

3 FeSO4 7H2O + 2Na2H AsO1 = Fe3"(AsO4)2

4

For the formation of a salt of the composition Fe"HASO, which is that assigned to the compound of the French Pharmacopoeia, 10 parts of crystallized ferrous sulphate would require, theoretically, 6-7 parts of anhydrous sodium arsenate, in accordance with the equation:

FeSO4,7H2O + Na2HASO, Fe"HASO, + Na2SO, + 7H2O

=

In order to ascertain the composition of the compounds which are officially recognized as iron arsenate, small quantities were prepared as nearly as possible in accordance with the directions of the respective pharmacopoeias, with the exception of the Mexican, dried uniformly at a temperature not exceeding 38°C., and submitted to analysis. In addition to these preparations, two representative samples of the B.P. product, as supplied by English manufacturers, were examined. The method of analysis employed was as follows:

(1) Estimation of the Ferrous Iron.-About 1 gramme of

1 The Italian Pharmacopoeia considers the official sodium arsenate to contain eight molecules of water, whereas the other pharmacopoeias state seven molecules.

28.6 Gm. of disodium hydrogen arsenate is the equivalent in arsenic content of 8:33 Gm. of potassium dihydrogen arsenate, the salt which the Mexican Pharmacopoeia directs to be employed.