Determination of 5-(p-hydroxyphenyl)-5-phenylhydantoin and studies relating to the disposition of phenytoin in man.
A gas chromatographic on-column methylation technique was developed for the routine laboratory determination of 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 three 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.
D055598:Chemical Phenomena; D002621:Chemistry; D002849:Chromatography, Gas / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D006868:Hydrolysis; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000652:urine
C001419:hydroxyphenytoin; D010672:Phenytoin