Measurement of mephenytoin (3-methyl-5-ethyl-5-phenylhydantoin) and its demethylated metabolite by selective ion monitoring

Mephenytoin (3-methyl-5-ethyl-5-phenylhydantoin) and its demethylated metabolite Nirvanol (5-ethyl-5-phenylhydantoin) were measured by a selective ion monitoring technique. This method was used in the analysis of both compounds in plasma from a patient receiving 50 mg and 400 mg of mephenytoin in single oral doses. Both compounds were extracted from plasma and ethylated prior to analysis by electron-impact mass spectrometry. Alkylation, using ethyl iodide in 2-butanone, occurred in the N-1 and N-3 positions of the hydantoin ring when concentrated KOH was added to the reaction mixture. The lower limits of quantitation for mephenytoin and Nirvanol were 10 ng/ml and 50 ng/ml, respectively, and were found to be reproducible within 8% upon repeated quantification.