Flash-heater ethylation of some antiepileptic drugs.

We describe a modification of the MacGee method [Anal. Chem. 42, 421 (1970)] for rapid determination of phenytoin (diphenylhydantoin) in plasma by gas-liquid chromatography, in which an ethylaing reagent is used instead of the more common methylating reagents. With this modification, several N-methylated antiepileptic drugs can be separated from their demethylated metabolites. Our results agree well with those of Butler and Waddell [Neurology 8, 106 (1958)], who showed that in patients receiving the N-methylated compounds mephenytoin and mephobarbital, the N-demethylated products, 5-ethyl-5-phenylhydantoin and phenobarbital are found in higher concentrations in plasma than are their respective parent drugs. The method is also useful for routine determinations of phenobarbital, primidone, and phenytoin in serum, cerebrospinal fluid, or saliva.