title: Characterization of the metabolites of carbamazepine in patient urine by liquid chromatography/mass spectrometry.
abstract: 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 micrograms/ml), trans-10, 11-dihydrodiol-CBZ (273.0-400.00 micrograms/ml), and CBZ (2.4-3.8 micrograms/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.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Maggs
authors.forename: M
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: N R
authors.initials: NR
authors.lastname: Kitteringham
authors.forename: B K
authors.initials: BK
authors.lastname: Park
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use / Q000652:urine*; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use / Q000652:urine*; D002853:Chromatography, Liquid; D004827:Epilepsy / Q000188:drug therapy / Q000652:urine; D005260:Female; D005965:Glucuronates / Q000652:urine; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction
chemical_list: D000927:Anticonvulsants; D005965:Glucuronates; D002220:Carbamazepine