Detection of new urinary exemestane metabolites by gas chromatography coupled to mass spectrometry

作者：Cavalcanti Gustavo de Albuquerque^*; Garrido Bruno Carius; Leal Felipe Dias; Padilha Monica Costa; de la Torre Xavier; de Aquino Neto Francisco Radler

来源：Steroids, 2011, 76(10-11): 1010-1015.

DOI：10.1016/j.steroids.2011.04.001

• Exemestane
• Metabolism
• GC-MS

Exemestane is an aromatase enzyme complex inhibitor. Its metabolism in humans is not fully described and there is only one known metabolite: 17 beta-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: 6 xi-hydroxy-6 xi-hydroxymethylandrosta-1,4-diene-3,17-dione (metabolite 1) and 6 xi-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, 3 xi-hydroxy-5 xi-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.

• 出版日期2011-10