title: Detection of new urinary exemestane metabolites by gas chromatography coupled to mass spectrometry.
abstract: Exemestane is an aromatase enzyme complex inhibitor. Its metabolism in humans is not fully described and there is only one known metabolite: 17β-hydroxyexemestane. In this work, excretion studies were performed with four volunteers aiming at the detection of new exemestane metabolites in human urine by gas chromatography coupled to mass spectrometry (GC-MS) after enzymatic hydrolysis and liquid-liquid extraction. Urine samples collected from four volunteers were analyzed separately. The targets of the study were mainly the 6-exomethylene oxidized metabolites. Two unreported metabolites were identified in both free and glucuconjugated urine fractions from all four volunteers, both of them were the result of the 6-exomethylene moiety oxidation: 6ξ-hydroxy-6ξ-hydroxymethylandrosta-1,4-diene-3,17-dione (metabolite 1) and 6ξ-hydroxyandrosta-1,4-diene-3,17-dione (metabolite 2). Furthermore, only in glucoconjugated fractions from all volunteers, one metabolite arising from the A-ring reduction was identified as well, 3ξ-hydroxy-5ξ-androst-1-ene-6-methylene-17-one (metabolite 3). The molecular formulae of all these metabolites were ascertained by the determination of exact masses using gas chromatography coupled to high resolution mass spectrometry (GC-HRMS). Moreover, all metabolites were confirmed using an alternative derivatization with methoxyamine and MSTFA/TMS-imidazole.
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Química, Programa de Pós-graduação em Química, LAB DOP-LADETEC, Ilha do Fundão, Avenida Athos da Silveira Ramos, 149, 21941-909, Rio de Janeiro, RJ, Brazil. gcavalcanti83@yahoo.com.br
authors.forename: Gustavo de Albuquerque
authors.initials: Gde A
authors.lastname: Cavalcanti
authors.forename: Bruno Carius
authors.initials: BC
authors.lastname: Garrido
authors.forename: Felipe Dias
authors.initials: FD
authors.lastname: Leal
authors.forename: Monica Costa
authors.initials: MC
authors.lastname: Padilha
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Torre
authors.forename: Francisco Radler
authors.initials: FR
authors.lastname: de Aquino Neto
mesh_terms: D000328:Adult; D000730:Androstadienes / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D055815:Young Adult
chemical_list: D000730:Androstadienes; C056516:exemestane