ABSTRACT
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.
Subject(s)
Oxymetholone/chemical synthesis , Oxymetholone/metabolism , Crystallography, X-Ray , Humans , Models, Molecular , Molecular Conformation , Oxymetholone/chemistrySubject(s)
Anabolic Agents/adverse effects , Oxymetholone/adverse effects , Anabolic Agents/chemical synthesis , Anabolic Agents/chemistry , Anabolic Agents/toxicity , Animals , Carcinogenicity Tests , Carcinogens/chemical synthesis , Carcinogens/chemistry , Carcinogens/pharmacology , Carcinogens/toxicity , Doping in Sports/legislation & jurisprudence , Female , Government Regulation , Guidelines as Topic , Humans , Male , Models, Biological , Occupational Exposure/adverse effects , Occupational Exposure/legislation & jurisprudence , Oxymetholone/chemical synthesis , Oxymetholone/chemistry , Oxymetholone/toxicity , Rats , Rats, Inbred F344 , Testosterone Congeners/chemical synthesis , Testosterone Congeners/chemistry , Testosterone Congeners/pharmacology , Testosterone Congeners/toxicity , United StatesABSTRACT
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.
