Single and multiple ion recording techniques for the analysis of diphenylhydantoin and its major metabolite in plasma

A method has been developed for single ion monitoring of diphenylhydantoin and its major metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin in plasma. A plasma extract is reacted with N, O-bis(trimethylsilyl)acetamide and single ion recording is carried out using a gas chromatograph mass spectrometer system. The mass value selected, m/e 254, is common to the TMS ethers of diphenylhydantoin and its principal metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin. The results indicate that one cause of an adverse reaction to diphenylhydantoin could be a reduced ability to hydroxylate the drug. Quantitative methods for the analysis of the drug and its major metabolite have also been developed. Diphenylhydantoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin can be analysed in plasma after addition of deuterium labelled internal standards and conversion to volatile derivatives for mass fragmentographic analysis. Diphenylhydantoin and its internal standard are analysed as the N, N-dimethyl derivative, and the hydroxylated metabolite and its internal standard are converted to a pertrimetylsilyl compound by reaction with N, O-bis-(trimethylsilyl)acetamide.