the advantage of measuring diphenylhydantoin directly without performing any chemical reaction on it. Thus, the use of hazardous chemicals, like diazomethane and BFrHF, is avoided. This method requires less than one hour for analysis of several samples, while other methods (2-4, 8) require several hours. Furthermore, this method, because of its direct nature, gives more accurate quantitative measurement of diphenylhydantoin over the other gas chromatographic method (6). The previous method requires the formation of the methyl derivative of diphenylhydantoin by reaction with diazomethane. This reaction gives the N-methyl derivative (9) of diphenylhydantoin in 25-38 yield (IO) which cannot be used as an accurate measurement of diphenylhydantoin in blood. This nonquantitative yield can be attributed to the lack of tautomerization of diphenylhydantoin to its enolic form which was shown by Carington and his co-workers (9) and more recently by Dudley and Bius (11). In addition, diazomethane is known to polymerize rapidly in the light to
produce high molecular weight polymers (I2-14), which in turn may interfere with the analysis of diphenylhydantoin and prevent an accurate qualitative and quantitative measurement. This gas chromatographic method has the advantage of simplicity and specificity over the colorimetric methods which require elaborate extraction or separation procedures to avoid interference by drugs frequently used with diphenylhydantoin such as phenobarbital. The absence of such interference in this method should make it useful in studying blood concentration of diphenylhydantoin in patients placed on multiple drug therapy. ACKNOWLEDGMENT
The authors thank Parke, Davis and Co., Detroit, Mich., for the diphenylhydantoin used in this study. RECEIVED for review April 21, 1969. Accepted June 11, 1969. Work supported by funds from the Public Health Service, Grant GM15956. ~~
(9) H. C. Carrington, C. H. Vasey, and W. S. Waring, J. Chem. SOC.,1953, 3105. (10) F. Arndt, Rev. Fuc. Sci. Univ. Istanbul, 9A, 19 (1944). (11) K. H. Dudley and D. L. Bius, J. Org. Chem., 34, 1133 (1969).
(12) K. R. Kopecky, G. S. Hammond, and P. A. Leermakers, J. Amer. Chem. SOC.,83, 2397 (1961). (13) C. H. Bawn and T. B. Rhodes, Trans. Furaduy Soc., 50, 934 (1954). (14) H. Meermein, Angew. Chem., A60, 78 (1968).
Substoichiometric Radioisotope Dilution Analysis of Tungsten as a Major Constituent in Molybdenum Containing MateriaIs Using To1uene3,4-Dithio1 L. T. McClendon and J. R. DeVoe Analytical Chemistry Diuision, National Bureau of Standards, Washington, D. C. 20234
THERE ARE SEVERAL reagents which produce colored complexes with tungsten ( I ) , thus providing the basis for numerous spectrophotometric methods for the determination of tungsten in various materials. However, these reagents also produce colored complexes with molybdenum, and because most tungsten containing materials also contain molybdenum, an interference problem exists with these photometric methods. Colorimetric methods which result in the formation of stoichiometric complexes can be adapted to radioisotope dilution techniques. The addition of excess complexing reagent to provide quantitative colorimetric analysis can often result in the formation of interfering metal complexes whose partition coefficient is close to that of the desired complex. The use of radioisotope ’dilution analysis with substoichiometric amounts of a complexing reagent, reduces the problem of interference by eliminating the need for quantitative separation. In addition, the radioisotope dilution technique is insensitive to problems of color instability (inherent or as the result of interferences). The technique involves the isolation of equal amounts of analyzed element before and after dilution of the radioisotope (by the analyzed element) (2). Measurement of specific activity of the radioisotope before and after dilution is facilitated by the substoichiometric technique, and (1) E. B. Sandell, “Colorimetric Determination of Trace Metals,” 3rd Ed., Interscience, New York, 1959. (2) J. Ruzicka and J. Stary, Tulunra, 8, 228 (1961).
1454
ANALYTICAL CHEMISTRY
the total amount of element is calculated using the standard substoichiometric radioisotope dilution equation,
x=
Y($
- 1)
where Y is the total amount of element in the radioisotope (known very accurately), and A I is the radioactivity obtained in the extract before dilution with nonactive isotope and A z is the activity obtained in the extract after dilution with nonactive isotope. The colored complexes formed by toluene-3,4-dithiol, often referred to as “dithiol,” were first reported by Hammence (3). Several workers (4-8) have developed photometric methods for determining tungsten and molybdenum in various materials over a span of years. Of course, the success of these methods is very dependent upon the control of the problems (mentioned above) that are inherent in photometric methods. Thus, arising from the need of several independent methods (3) J. H. Hammence, Analyst, 65, 152 (1940). (4) B. Bagshawe and R. J. Truman, ibid., 72, 189 (1947). (5) P. Greenberg, ANAL.CHEM., 29, 896 (1957). (6) S. H. Allen and M. B. Hamilton, Anal. Chim. Acta, 7 , 483 (1952). (7) C. S. Piper and R. S. Beckwith, J. SOC. Chem. Ind., 67, 374 (1948). (8) E. W. Hobart and E. P. Hurley, Anal. Chim. Acta, 27, 142 (1962).
Table I. Results of Tungsten in Ideal Solutions mg (W) added
mg (W) found
2.200 1.968 0.984 0.492
2.205 1.961 0.977 0.484
ti l/n'mg
No. of determinations
0.009
0.009
0.010 0.004
0.008
3 4 3 4
Std dev single determination
0.004
0.009
0.008
Table 11. Tungsten Results Std dev %W
Sample 81 0.004655 g
#2 0,005045 g #3 0,004890 g #4
0.004885 g
a
individual runs
z
Average
of single
determination
79.54 78,57 79.60 78.64
79.08
0.558
0.48
79.22 79.76 79.09
79.36
0.355
0.56
79.95 79.67 79.30
79.64
0.325
0.56
79.26 78.87 79.55
79.22
0.340
0.56
79.315
0.43*
Grand average,
* Pooled estimate of standard deviation. in our laboratory for tungsten determinations in the presence of molybdenum, we developed a radioisotope dilution procedure for tungsten using dithiol. EXPERIMENTAL
Apparatus. The apparatus consisted of 60-ml separatory funnels, 2 in. X 2 in. NaI well-type scintillation counter, and 1-dram vials which were used for counting vessels. Reagents. Tungsten-181 high specific activity radioisotope was obtained from Nuclear Science and Engineering Corp. Tungsten standard solution was prepared by dissolving the desired amount of tungsten powder (99.9 % purity) in H F + "OB; then heating to drive off NO2 fumes and diluting to volume with lMHC1. A 0.5% solution of toluene3,4-dithiol was prepared in a basic medium as described by Hobart and Hurley (8). HC1 solution with a specific gravity of 1.06 was prepared by making a 3.48M HC1 solution. Titanous sulfate solution was prepared fresh daily, by dissolving 1.0 gram of titanium metal in 100 ml of 3N HzS04 with heating. All other chemicals used were reagent grade quality. Procedure. The general tungsten procedure, with no molybdenum present, is as follows: In a separatory funnel add an accurately known weight of tungsten ( Y ) - 0.492 mg in this procedure, IBIW (-106 CPM in order to achieve good counting statistics in short time period) and varying amounts of tungsten from synthetic solution or from the sample if performing an analysis. Mix well. Add 25 ml of hot titanous sulfate and 20 ml of 11.7M HCl. Mix well. Add 0.20 ml of 0.5% dithiol solution and mix well. Allow 90 minutes for the mixture to cool to room temperature and to assure equilibrium, then extract with 10 n l of CHC1,. Take 0.5-ml aliquots of both phases for counting to make sure no anomalous effects occur.
Tungsten Analysis in NBS W-MO Alloy (SRM-480). Each sample (-5 mg) was etched in a freshly prepared mixture of 10 ml conc. HNO,, 10 ml conc. H2S04 and 10 ml H 2 0 for 15 minutes. The samples were rinsed, dried, and weighed. The weight loss from this etching step is very small (
