Use of stable isotopes in the study of pharmacokinetics of drugs by mass fragmentography II: Detailed examination of pharmacokinetics of a single oral dose of phenytoin in humans.
To study the pharmacokinetics of phenytoin in detail, a mass fragmentographic method was applied for the precise, sensitive, and specific analysis of phenytoin, 5-(4-hydroxyphenyl)-5-phenylhydantoin, and 5-(4-hydroxyphenyl)-5-phenylhydantoin glucuronide in plasma and urine after administration of a single oral dose of phenytoin to two healthy volunteers. Salivary phenytoin concentrations also were measured. Phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin were analyzed after the addition of deuterium-labeled internal standards and conversion to volatile methyl derivatives for mass fragmentographic analysis. The lower limit of detection was approximately 10 ng/ml. The simultaneous pharmacokinetic analysis of the plasma levels and urinary excretion data of phenytoin and its major metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin, yielded detailed information about the pharmacokinetics of phenytoin.
D000284:Administration, Oral; D000328:Adult; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000378:metabolism*; D012044:Regression Analysis; D012463:Saliva / Q000032:analysis
D010672:Phenytoin; D003903:Deuterium