title: An S-mephenytoin cysteine conjugate identified in urine of extensive but not of poor metabolizers of S-mephenytoin.
abstract: 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 after a single dose of 100 mg racemic mephenytoin. High performance liquid chromatography purification, followed by gas chromatographic, mass spectrometric and amino acid analyses showed that the isolated compound is a cysteine conjugate of S-mephenytoin. The significant mass spectrometric ions have been confirmed in three additional extensive metabolizers of S-mephenytoin, but were not detectable in urine from three poor metabolizer subjects. The exact structure of the conjugate is unknown, but we suggest that an S-N bond between cysteine and S-mephenytoin is formed via an oxidative radical mechanism catalyzed by CYP2C19.
authors.affiliation: Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Tybring
authors.forename: J
authors.initials: J
authors.lastname: Nordin
authors.forename: T
authors.initials: T
authors.lastname: Bergman
authors.forename: L
authors.initials: L
authors.lastname: Bertilsson
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008617:Mephenytoin / Q000493:pharmacokinetics* / Q000652:urine; D010641:Phenotype
chemical_list: D003545:Cysteine; D008617:Mephenytoin