AN S-MEPHENYTOIN CYSTEINE CONJUGATE IDENTIFIED IN URINE OF EXTENSIVE BUT NOT OF POOR METABOLIZERS OF S-MEPHENYTOIN

A conjugate of S-mephenytoin excreted in urine of extensive but not of poor metabolizers of S-mephenytoin has previously been reported, This conjugate, which is easily hydrolysed back to S-mephenytoin, has now been isolated and identified in urine from one extensive metabolizer a fter a single dose of 100 mg racemic mephenytoin, High performance liq uid chromatography purification, followed by gas chromatographic, mass spectrometric and amino acid analyses showed that the isolated compou nd is a cysteine conjugate of S-mephenytoin. The significant mass spec trometric ions have been confirmed in three additional extensive metab olizers of S-mephenytoin, but were not detectable in urine from three poor metabolizer subjects, The exact structure of the conjugate is unk nown, but we suggest that an S-N bond between cysteine and S-mephenyto in is formed via an oxidative radical mechanism catalyzed by CYP2C19.