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0090-9556/97/2503-0275-0280$02.00/0
DRUG METABOLISM AND DISPOSITION
Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics
Vol. 25, No. 3

Characterization of the Metabolites of Carbamazepine in Patient Urine by Liquid Chromatography/Mass Spectrometry

J. L. Maggs, M. Pirmohamed, N. R. Kitteringham, and B. K. Park

Department of Pharmacology and Therapeutics, University of Liverpool

The urinary metabolites of carbamazepine (CBZ) in epileptic patients receiving long-term drug treatment have been characterized by LC/MS. CBZ-10,11-epoxide (9.6-15.0 µg/ml), trans-10,11-dihydrodiol-CBZ (273.0-400.00 µg/ml), and CBZ (2.4-3.8 µg/ml) were measured by HPLC. The secondary N-glucuronide of CBZ, four phenolic O-glucuronides (including those of 2- and 3-OH-CBZ), two additional OH-CBZ O-glucuronides, and the N-glucuronide of CBZ-10,11-epoxide constituted the products of either direct conjugation or preliminary monoxygenation. Derivatives of these monoxygenated compounds, which were characterized as O-glucuronides, were represented by dihydroxylated (catechol) CBZ and its putative O-methyl metabolite and by 10,11-dihydrodiol-CBZ. 10,11-Dihydro-10-OH-CBZ O-glucuronide, a metabolite thought to be excreted only by uremic subjects, was not found. More complicated biotransformations of the 10,11-ene moiety were revealed by two carbinol products of azepine ring contraction: 9-OH-methyl-10-carbamoyl acridan and an hydroxylated derivative thereof, which were excreted as O-glucuronides. No polar sulfur-containing metabolites that might serve as indicators of reactive intermediate formation were found in human urine.

Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.