Chiral aspects of the human metabolism of ethosuximide.
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.
Millership
J S
JS
Clinical and Practice Research Group, The School of Pharmacy, Medical Biology Centre, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland. j.millership@qub.ac.uk
Mifsud
J
J
Galea
D
D
McRoberts
W C
WC
Hamilton
J T G
JT
D000927:Anticonvulsants / Q000378:metabolism*; D005013:Ethosuximide / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans
D000927:Anticonvulsants; D005013:Ethosuximide