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
Baba, S.; Goromaru, T.; Yamazaki, K.; Kasuya, Y.
Journal of Pharmaceutical Sciences 69(11): 1300-1307
ISSN/ISBN: 0022-3549 PMID: 7452459 DOI: 10.1002/jps.2600691118
To study the pharmacokinetics of the anticonvulsant 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 2 healthy volunteers. Salivary phenytoin concentrations 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 .apprx. 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.