Determination of 5-(P-Hydroxyphenyl)-5-Phenylhydantoin and Studies Relating to the Disposition of Phenytoin in Man

Publisher Website
Google Scholar
Abstract
A gas chromatographic on-column methylation technique was developed for the routine laboratory determination of the anticonvulsant 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH), the principal urinary product of phenytoin (PHT) metabolism in man. 5-(p-Hydroxyphenyl)-5-(p-tolyl)hydantoin (HMPPH), a new internal standard, was synthesized and evaluated against 5-phenyl-5-(p-tolyl)hydantoin (MPPH), the compound normally used as the internal standard in p-HPPH assays. HMPPH withstood the challenges of intralaboratory quality control checks and tests of precision of p-HPPH values at times when MPPH provided erratic and unreliable values. Both an enzyme and acid treatment of urine were studied for the purpose of hydrolysis of p-HPPH-glucuronide, the form in which p-HPPH is excreted in urine. The use of both treatments in studies of 3 different patient urines pointed to the conclusion that acid-catalyzed decomposition of PHT dihydrodiol, a minor urinary metabolite of PHT in man, was unimportant from the analytical point of view, contributing little if anything to total urinary p-HPPH content. Some aspects of PHT disposition, as evidenced by studies of PHT plasma levels and p-HPPH urinary outputs in individual patients, are discussed.

This publication has 0 references indexed in Scilit: