RESUMO
A long-term metabolite of the doping agent oxymetholone (OXM-M2, 17ß-hydroxymethyl-2,17α-methyl-18-norandrost-13-en-3-one) which has been identified by GC-MS/MS was synthesized from commercially available materials. Two efficient synthetic routes to access both C-17 epimers of tentative metabolites were developed. The identity and molecular configuration of the in vivo metabolite: 17ß-hydroxymethyl-2α,17α-methyl-18-norandrost-13-en-3-one was confirmed by single crystal X-ray diffraction.
Assuntos
Oximetolona/síntese química , Oximetolona/metabolismo , Cristalografia por Raios X , Humanos , Modelos Moleculares , Conformação Molecular , Oximetolona/químicaAssuntos
Anabolizantes/efeitos adversos , Oximetolona/efeitos adversos , Anabolizantes/síntese química , Anabolizantes/química , Anabolizantes/toxicidade , Animais , Testes de Carcinogenicidade , Carcinógenos/síntese química , Carcinógenos/química , Carcinógenos/farmacologia , Carcinógenos/toxicidade , Dopagem Esportivo/legislação & jurisprudência , Feminino , Regulamentação Governamental , Guias como Assunto , Humanos , Masculino , Modelos Biológicos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/legislação & jurisprudência , Oximetolona/síntese química , Oximetolona/química , Oximetolona/toxicidade , Ratos , Ratos Endogâmicos F344 , Congêneres da Testosterona/síntese química , Congêneres da Testosterona/química , Congêneres da Testosterona/farmacologia , Congêneres da Testosterona/toxicidade , Estados UnidosRESUMO
Two major unconjugated acidic metabolites of oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one, 1), namely, 17 beta-hydroxy-17 alpha-methyl-2,3-seco-5 alpha-androstane-2,3-dioic acid (2) and 3 alpha,17 beta-dihydroxy-17 alpha-methyl-5 alpha-androstane-2 beta-carboxylic acid (6a), were detected by gas chromatography/mass spectrometry in urine samples collected after oral administration of 1 to a human volunteer. Reference steroid 2 was synthesized and identified. The identification of urinary metabolite 6a was based on the synthesis of its stereoisomers and the isomerization of the methyl ester 6b to its 2-epimer, 3 alpha,17 beta-dihydroxy-17 alpha-methyl-5 alpha-androstane-2 alpha-carboxylic acid methyl ester (9b). The mechanisms accounting for the formation of these acidic metabolites are discussed.
