title: Identification of [14C]fluasterone metabolites in urine and feces collected from dogs after subcutaneous and oral administration of [14C]fluasterone.
abstract: 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-(14)C]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 4alpha-hydroxy-16alpha-fluoro-5-androsten-17beta-ol and X(alpha or beta)-4alpha-dihydroxy-16alpha-fluoro-5-androsten-17beta-ol. The identification of the monoglucuronide conjugate of 4alpha-hydroxy-16alpha-fluoro-5-androsten-17beta-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 (16alpha-fluoro-5-androsten-17beta-ol and 16alpha-fluoro-5-androsten-17alpha-ol) and 4alpha-hydroxy-16alpha-fluoro-5-androsten-17beta-ol that was present in urine in glucuronide form.
authors.affiliation: Analytical Chemistry and Pharmaceutics Group, RTI International, 3040 Cornwallis Road, Research Triangle Park, NC 27709-2194, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Burgess
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Green
authors.forename: Judith M
authors.initials: JM
authors.lastname: Hill
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhan
authors.forename: Matthew
authors.initials: M
authors.lastname: Lindeblad
authors.forename: Alexander
authors.initials: A
authors.lastname: Lyubimov
authors.forename: Izet M
authors.initials: IM
authors.lastname: Kapetanovic
authors.forename: Arthur
authors.initials: A
authors.lastname: Schwartz
authors.forename: Brian F
authors.initials: BF
authors.lastname: Thomas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D004285:Dogs; D004912:Erythrocytes / Q000378:metabolism; D005243:Feces / Q000737:chemistry*; D005966:Glucuronidase / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism; D007279:Injections, Subcutaneous; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D013429:Sulfatases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D020719:Glucuronides; D003687:Dehydroepiandrosterone; D013429:Sulfatases; D005966:Glucuronidase; C106219:5-androstene-16-fluoro-17-one