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Chiral aspects of the human metabolism of ethosuximide
Author(s) -
Millership J. S.,
Mifsud J.,
Galea D.,
McRoberts W. C.,
Hamilton J. T. G.
Publication year - 2005
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.454
Subject(s) - ethosuximide , metabolite , derivatization , enantiomer , chemistry , chromatography , gas chromatography–mass spectrometry , chemical ionization , gas chromatography , mass spectrometry , electron ionization , stereochemistry , ionization , organic chemistry , anticonvulsant , biochemistry , medicine , ion , psychiatry , epilepsy
Ethosuximide is a chiral drug substance primarily indicated for the treatment of absence seizures. This drug is used clinically as the racemate. The human urinary metabolites of ethosuximide (I) have been studied using chiral gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The metabolites identified were the previously reported unchanged ethosuximide (I) enantiomers, all four stereoisomers of 2‐(1‐hydroxyethyl)‐2‐methylsuccinimide (II), and the four stereoisomers of 2‐ethyl‐3‐hydroxy‐2‐methylsuccinimide (III). Through chemical derivatization methodology and GC/MS (using electron impact ionization [EI] and chemical ionization [CI] techniques) two enantiomers of a previously unreported metabolite of ethosuximide, 2‐ethyl‐2‐hydroxymethylsuccinimide (VI), have been identified. Copyright © 2005 John Wiley & Sons, Ltd.