Recent studies on the metabolic disposition of diphenylhydantoin ( DPH) have been largely dependent upon blood level assays with the use of the colorimetric procedure developed by Dill and associates 5 or the ultraviolet absorbance procedure described by Svensmark and associates. ' 14The colorimetric procedure appears to be the method of choice because of its high degree of specificity. 6 Little attention has been directed toward the excretion pattern of urinary metabolites, mainly because of the lack of satisfactory analytical proce-A preliminary report of this work appeared as an abstract in Clin. Res. 16:464, 1968. Received for publication Jan. 31, 1969.Accepted for publication April 2, 1969. 498dures. The principal urinary excretion product of DPH was identified by Butler 2 as 5-( p-hydroxyphenyl) -5-phenylhydantoin ( HPPH), which is conjugated with glucuronic acid and excreted in the urine. 9 Estimates of HPPH excretion by Butler/ Maynert,9 Panalaks, 12 and Kutt and associates 7 ranged from 45 per cent to 70 per cent of the daily dose of DPH; however, none of these studies involved an examination of HPPH excretion over time periods less than 24 hours in duration. This has been done in the present study with a new, highly specific gas-chromatography procedure to assay HPPH in urine 3 in parallel with colorimetric measurement of DPH plasma levels following single intravenous doses of DPH to normal human subjects.

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