T H E JOURNAL OF I N D U S T R I A L A N D ENGINEERING C H E M I S T R Y
624
Vol. 14. No. 7
Estimation of Sulfate in By Elias Elvove HYGIENIC LABORATORY, U. S. PXJBLIC HEALTH SERVICE, WASHINGTON, D. C.
A method is described whereby the sulfate i n neoarsphenamine can be determined without the preliminary precipitation, filtration, etc., of the formaldehyde sulfoxylic acid derioatioe of the arseno base which is called for by the method of Raiziss and Falkoo. The results by the latter method, howeoer, are higher than by the direct method, which increase is probably due to further oxidation to sulfate of sulfur present in lower stages of oxidation, during the preliminary precipitation, filtration, and washing of the precipitate. The direct method was used i n determining the sulfatc in thirty-four samples of neoarsphenamine from ten manufacturers. When calculated as NatSOa,the results showed a variation f r o m a minimum of 1.4 per cent to a maximum of 17.6%per cent. Averaging the
results obtained with each manufacturer’s samples separately these averages gaue a minimum of 1.76 per cent and a maximum of 5.82 per cent. It appears, howeoer, that the manufacturer can control his process so that his product will not oary oery much i n its sulfate content. Thus the auerage sulfate content (calculated as Na~S04)of six samples of neoarsphenamine f r o m one manufacturer was 3.52 per cent while, with the exception of only one sample, the largest difference was only 0.32 per cent; and including this one sample, the largest difference was only 0.73 per cent, although the samples examined c o w a period of manufacture of about three years, during which time there were produced about six hundred and eighty-fiue different lot numbers.
plan of procedure has recently been described by Raiziss and Falkov3 for determining the distribution of sulfur in ne~arsphenamine.~This procedure requires four gravimetric determinations, one of which aims to determine the sulfur which is present as sulfate in the original sample. This is carried out as follows:
NEW PROCEDURE About 200 cc. of distilled water were boiled down to about 150 cc. in a beaker of about 400-cc. capacity. The boiling was stopped, but while the water was still hot (75’ to 85’ C.) a 0.2-g. sample of neoarsphenamine was added and quickly dissolved with the aid of a stirring rod. This was followed quickly by 10 C C . ~of N HCl. The beaker was then covered with a watch glass and the contents boiled until the volume was reduced to about 50 cc. It was then diluted with distilled water to about 150 cc., heated to boiling, and to the gently boiling solution there were added slowly, from a pipet,g 15 cc. of 0.05 M BaC12. The precipitate of barium sulfate was allowed to settle over night and then was filtered and weighed. COMPARISON WITH RESULTSOF RAIZISSAND FALKOV
A
0.3 g. of the neoarsphenamine is dissolved in about 25 cc. of water, the solution cooled in ice, and 5 cc. of dilutea hydrochloric acid are added. After standing 15 min. in the cold, the precipitate is filtered off quantitatively by suction through an asbestos and cotton filter6 and washed many times with small amounts of 1 per cent hydrochloric acid. The filtrate, together with the combined washings, is then used for determining the sulfate by precipitation with barium chloride, etc.
In order to make it practicable to apply such tests in the routine examination of neoarsphenamine, it was thought desirable to simplify these determinations. As a result of some preliminary experiments, it was found that the determination of the sulfate can be carried out on the neoarsphenamine solution directly without the preliminary precipitation, filtration, and washing of the formaldehyde sulfoxylic acid derivative7 of the arseno base. In addition to saving time and labor, this direct method appears to have also the advantage that it avoids the possible error which may result from further oxidation to sulfate of the sulfur present in lower stages of oxidation, during the preliminary treatment which is called for by the method of Raiziss and Falkov. Received March 21, 1922. Approved for publicatioa by the Surgeon General. a J . Biol. Chem., 46 (1921), 209. 4 In the literature. neoarsphenamine is usually given the formula: 1
2
As
As
HC
CH
HC
CH
HzNC
CH
HC
CNH.CHz0.SONa
I
I
I
I
C ’‘
I
OH
I
OH
It is now recognized, however, that the commercial neoarsphenamine is not the single chemical compound represented by the above formula but probably a mixture of this compound, a similar compound in which both amino groups have been combined with the formaldehyde sulfoxylate grouping, some uncombined sulfoxylate and various other impurities, the exact nature of which has not yet been determined. 6 2 N €IC1 was used in the determinations reported in this paper, 6 J . B i d . Chem., 18 (1814), 287. 7 3.3’-Diamino-4,4’-dihydroxyarsenobenzene-N-methylenesulfinic acid.
METHOD This sulfate amine. and by
procedure was applied to the determination of the in a number of commercial samples of neoarsphenSome comparative results by this direct method that of Raiziss and Falkov are given in Table I.
TARLE I-COMPARATIVERESULTSFOR SULFATE BY DIRECTMETHOD AND PRELIMINARY PR~CIPITATION Wt. of BaSOi MANURACTLJRER LOT NO. METHOD ME. A 1 Direct 10.6 R. and F.l 26.8 A 2 Direct 10.5 R. and F. 26.8 B 1 Direct 7.9 R. and F. 19.2 B 2 Direct 7.6 R. and F. 20.3 C 1 Direct 6.6 R. and F. 24.8 C 2 Direct 57.9 R. and F. 64.1 D 1 Direct 5.5 R. and F. 20.7 D 2 Direct 6.4 R. and F. 17.5 1 Preliminary precipitation, etc. AFTER
Difference Mn. 16.2 16.3
11.3 12.7 18.2 6.2 15.2
11.1
It will be noted that the amounts of sulfate found by this direct method are lower than the corresponding amounts found by the method of Raiziss and Falkov, which is in har8 Usually the precipitate which forms a t first redissolves when the last portion of the acid has been added and the contents of the beaker mixed with the stirring rod. In the case of several samples, however, i t was found necessary to add more than the 10 cc. of N HCl in crder completely to redissolve the precipitate. In such cases, therefore, 20 cc. of the N H C l were added. 8 The reason for using a comparatively dilute solution of barium chloride of known value was t o facilitate the aim ultimately to carry out some of the sulfur determinations volumetrically.
T H E JOURNAL OF I N D U S T R I A L A N D ENGINEERING CHEMISTRY
July, 1922
many with what we might expect, since the preliminary treatment (precipitation, filtration, etc.) called for by the latter method may increase the amount of sulfate through further oxidation to sulfate of the sulfur present in lower stages of oxidation, especially as it appears that the properties of this precipitate render its complete filtration and washing a comparatively very slow process.
ADDITIONOF SULFATE In order to prove that the lower results for sulfate by the direct method were not due to loss of sulfate caused by the preliminary boiling of the solution, known amounts of sulfate were added to some of the samples of neoarsphenamine which were used for obtaining the results given in Table I, and the total sulfate then determined by the direct method. The results obtained are given in Table 11. TABLE 11-RESULTS
DIRECTMETHOD WITH SAMPLES OF NEOARSPHENAMINE TO WHICH KNOWNAMOUNTS OF SULFATE WERE ADDED NaeSO4 Additional NazSOa Weight of MANUPAC- Added BaSOa Equivalent NatSOr Found Difference TUBER Grams Grams Grams Grams Grams A None 0.0106 0.0068 .... A 0.0142 0.0346 0.0211 0.0146 0:0004 A 0.0711 0.1269 0,0772 0,0707 -0.0004 B None 0.0076 0.0046 .... .... B 0.0142 0.0304 0.0185 0.0139 -0.0003 B 0.0711 0.1226 0.0746 0.0700 -0,001 1 C Xone 0,0579 0,0382 .... C 0,0142 0.0797 0.0485 o:Oii3 -0.000~ C 0.0711 0.1731 0.1063 0.0701 -0.0010 BY
The results given in Table I1 show that the added sulfate was recovered fairly quantitatively.lo And although there seems to be a tendency for the results to be about a milligram or less under the true value, this, however, could not account for the very much greater differences (over 11 mg. in most cases) shown in Table I. This would indicate, therefore, that the higher results by the method of Raiziss and Falkov as compared with those obtained by the direct method are due to further oxidation to sulfate of the sulfur present in lower stages of oxidation, during the preliminary precipitation, filtration, etc., required by the former method.
TABLE 111-DETERMINATIONO F SULFATE
MANUBACITuRER4 A A A A A A
IN
625 VARIOUS COMMERCIAL
. 1 2 3 4 5 6
3 25 3 20 3 45 3.55 3.45 4.25
Av. 3 . 5 2
1 2 3 6
3.05 2 40 2 30 3.75 2 45 2 30
Av. 2 . 7 1
D D D D
1 2 3 4
1.70 1.95 2.00 1.40
Av. 1 . 7 6
E E
1 2 3
3.25 2.65 2.40
Av. 2 . 7 7
F F F
1
2
G G
1 2
5.75 5.QO
Av. 5 . 8 2
EH
1 2
3.30 5.25
Av. 4 . 2 7
B B
B R B
B
2
SAM-
PERCENTAGE
4
C C C C
C C
E
3
1.65 1 1 4.20 J 1 Omitting Lot 2, which evidently contained a rather exceptionally large amount of sulfate.
I
exceptional. But this variation is apparently not unavoidable, since some manufacturers ( e . g., A) produce a product which is fairly uniform12in its sulfate content. On the other hand, in the case of some other manufacturers (e. g., C), the variation is comparatively very large. If we omit the results obtained with the samples from I and J, since there was only one sample of each examined, and average the results obtained with each manufacturer’s samples separately, TESTSOF METHOD O N PRODUCT FROM TENMANUFACTURERS these averages give a minimuin of 1.76 per cent and a maxiSince it is now recognized that the commercial neoarsphen- mum of 5.82 per cent. These figures, therefore, may be amine is not the single chemical compound which it had been taken as indicating approximately the average limits of represented to be, namely,I1 sodium 3,3’-diamino4,4’-di- sulfate content when we consider the products of different hydroxy-arsenobenzene-K-methylenesulfinate, but that it is manufacturers. While the primary object of the sulfate determination is really a mixture of more or less varying composition, it appeared desirable to try out the direct method described in to obtain figures which, together with other analytical data, this paper on a comparatively large number of samples rep- will enable us to calculate the distribution of the sulfur in resenting the products of as many different manufacturers the neoarsphenamine, it would seem that it might also serve as possible. The results obtained with thirty-four samples as a sort of partial index of the uniformity of the conditions of neoarsphenamine from 10 manufacturers are given in of manufacture. Furthermore, although most of the sulfate can probably be traced to impurities in the sodium formalTable 111. The results given in Table 111 show that the amounts of dehyde sulfoxylate, still it is quite possible that a t least some sulfate in commercial samples of neoarsphenamine vary of the sulfate, especially in the case of a manufacturer whose considerably. Calculated as Na2S04,it may be as low as neoarsphenamine shows a comparatively large variation in 1.4 per cent (D, No. 4) or as high as 17.6 per cent (C, No. 2). its sulfate content, is the result of further oxidation to sulThe latter amount of sulfate, however, seems to be rather fate of sulfur present in lower stages of oxidation, during some stage of the process of manufacture or handling. And 10 One might argue that the neoarsphenamine solution affects the solusince when neoarsphenamine is partly oxidized it gives rise bility of the barium sulfate so that a certain amount of the barium sulfate is used up, in the case of the direct method, for saturating the solution. to a comparatively highly toxic13 product and since conditions If this were so, one could recover quantitatively the added sulfate and yet which will bring about such oxidation might also cause an not disprove the hypothesis that the direct method gives lower results for increase of the sulfate content, it would seem that a comparathe reason that the introduction of the neoarsphenamine increases the solutively large increase in the sulfate, which cannot be explained bility of the barium sulfate. I n order t o see whether there is any basis for such an argument, about 30 mg. of precipitated barium sulfate were added as due to extraneous sources, might be regarded with SUSto a neoarsphenamine (“A,” KO. 1) solution of a concentration, acidiiy, picion. The sulfate determination might, therefore, also and other conditions approximately Tirnilar t o those which we have when serve for this purpose. the sulfate is determined by the direct method. The volume of about 150 cc. was boiled down to about 60 cc. It was then diluted again to about 150 cc., heated to boiling, allowed to settle, etc., just as in the case of the sulfate determination. Results showed t h a t the introduction of the neoarsphenamine did not increase appreciably the solubility of the barium sulfate. 11 Morgan, “Organic Compounds of Arsenic and Antimony,” 1918, 251.
1 2 And in face of the fact t h a t the samples tested cover a period of manufacture of about 3 yrs. 13 Thus, for example, Roth [Public Heallh Reporls, 95 (19201, 22051 found that shaking an aqueous solution of neoarsphenamine for 10 min. may increase its toxicity over fourfold.
