PT - JOURNAL ARTICLE AU - Burgess, Jason P. AU - Green, Jonathan S. AU - Hill, Judith M. AU - Zhan, Qiao AU - Lindeblad, Matthew AU - Lyubimov, Alexander AU - Kapetanovic, Izet M. AU - Schwartz, Arthur AU - Thomas, Brian F. TI - Identification of [<sup>14</sup>C]Fluasterone Metabolites in Urine and Feces Collected from Dogs after Subcutaneous and Oral Administration of [<sup>14</sup>C]Fluasterone AID - 10.1124/dmd.108.023614 DP - 2009 May 01 TA - Drug Metabolism and Disposition PG - 1089--1097 VI - 37 IP - 5 4099 - http://dmd.aspetjournals.org/content/37/5/1089.short 4100 - http://dmd.aspetjournals.org/content/37/5/1089.full SO - Drug Metab Dispos2009 May 01; 37 AB - The objective of this research was the identification of the metabolic profile of fluasterone, a synthetic derivative of dehydroepiandrosterone, in dogs treated orally or subcutaneously with [4-14C]fluasterone. Separation and characterization techniques used to identify the principal metabolites of fluasterone in urine and feces included high-performance liquid chromatography (HPLC), liquid scintillation spectrometry, HPLC/tandem mass spectrometry, and NMR. In urine, the majority of the radioactivity was present as two components that had apparent molecular weights consistent with their tentative identification as monoglucuronide conjugates of 4α-hydroxy-16α-fluoro-5-androsten-17β-ol and X(α or β)-4α-dihydroxy-16α-fluoro-5-androsten-17β-ol. The identification of the monoglucuronide conjugate of 4α-hydroxy-16α-fluoro-5-androsten-17β-ol was also supported by NMR data. In support of this identification, these metabolites were cleaved with glucuronidase enzyme treatment, which gave rise to components with molecular weights again consistent with the aglycones of a monohydroxylated, 17-keto reduced (dihydroxy) fluasterone metabolite and a dihydroxylated, 17-keto reduced (trihydroxy) fluasterone metabolite. In feces, nonconjugated material predominated. The primary metabolites eliminated in feces were the two hydroxy fluasterone metabolites arising from 17-reduction (16α-fluoro-5-androsten-17β-ol and 16α-fluoro-5-androsten-17α-ol) and 4α-hydroxy-16α-fluoro-5-androsten-17β-ol that was present in urine in glucuronide form. U.S. Government work not protected by U.S. copyright.