title: Studies on anabolic steroids--12. Epimerization and degradation of anabolic 17 beta-sulfate-17 alpha-methyl steroids in human: qualitative and quantitative GC/MS analysis.
abstract: The epimerization and dehydration reactions of the 17 beta-hydroxy group of anabolic 17 beta-hydroxy-17 alpha-methyl steroids have been investigated using the pyridinium salts of 17 beta-sulfate derivatives of methandienone 1, methyltestosterone 4, oxandrolone 7, mestanolone 10 and stanozolol 11 as model compounds. Rearrangement of the sulfate conjugates in buffered urine (pH 5.2) afforded the corresponding 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes in a ratio of 0.8:1. These data indicated that both epimerization and dehydration of the 17 beta-sulfate derivatives were not dependent upon the respective chemical features of the steroids studied, but were instead inherent to the chemistry of the tertiary 17 beta-hydroxy group of these steroids. Interestingly, in vivo studies carried out with human male volunteers showed that only methandienone 1, methyltestosterone 4 and oxandrolone 7 yielded the corresponding 17-epimers 2, 5 and 8 and the 18-nor-17,17-dimethyl-13(14)-enes 3, 6 and 9 in ratios of 0.5:1, 2:1 and 2.7:1, respectively. No trace of the corresponding 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes derivatives of mestanolone 10 and stanozolol 11 was detected in urine samples collected after administration of these steroids. These data suggested that the in vivo formation of the 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes derivatives of 17 beta-hydroxy-17 alpha-methyl steroids is also dependent upon phase I and phase II metabolic reactions other than sulfation of the tertiary 17 beta-hydroxyl group, which are probably modulated by the respective chemical features of the steroidal substrates. The data reported in this study demonstrate that the 17-epimers and 18-nor-17,17-dimethyl-13(14)-enes are not artifacts resulting from the acidic or microbial degradation of the parent steroids in the gut as previously suggested by other authors, but arise from the rearrangement of their 17 beta-sulfate derivatives. Unchanged oxandrolone 7 was solely detected in the unconjugated steroid fraction whereas unchanged steroids 1, 4 and 11 were recovered from the glucuronide fraction. These data are indirect evidences suggesting that the glucuronide conjugates of compounds 1 and 4 are probably enol glucuronides and that of compound 11 is excreted in urine as a N-glucuronide involving its pyrazole moiety. The urinary excretion profiles of the epimeric and 18-nor-17,17-dimethyl-13(14)-ene steroids are presented and discussed on the basis of their structural features.
authors.affiliation: Institut National de la Recherche Scientifique, INRS-Santé, Université du Québec, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Bi
authors.forename: R
authors.initials: R
authors.lastname: Massé
mesh_terms: D000328:Adult; D045930:Anabolic Agents / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D006914:Hydroxysteroids / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008696:Methandrostenolone / Q000378:metabolism / Q000652:urine; D008777:Methyltestosterone / Q000378:metabolism / Q000652:urine; D010074:Oxandrolone / Q000378:metabolism / Q000652:urine; D013197:Stanozolol / Q000378:metabolism / Q000652:urine; D013455:Sulfur / Q000378:metabolism
chemical_list: D045930:Anabolic Agents; D005965:Glucuronates; D006914:Hydroxysteroids; D013196:Dihydrotestosterone; D013197:Stanozolol; D013455:Sulfur; D010074:Oxandrolone; D008696:Methandrostenolone; C008376:mestanolone; D008777:Methyltestosterone