title: Metabolism of (2S)-pterosin A: identification of the phase I and phase II metabolites in rat urine.
abstract: The metabolic profile of the potent hypoglycemic agent, (2S)-pterosin A (1), in rat urine via intragastrical oral administration was investigated. In total, 19 metabolites (M1-M19) were identified. Among these, 16 metabolites were characterized by high-performance liquid chromatography solid-phase extraction-tube transfer-NMR, and seven metabolites were further isolated from the treated urine to enable further structural determination. Twelve of these are new compounds. The phase I metabolites of 1 were formed via various oxidations at positions C-3, C-10, C-12, C-13, or C-1 followed by decarboxylation of C-10 or C-14, and lactonization at C-12/C-14 or C-14/C-12. The phase II metabolites were glucuronide conjugates from the parent compound or phase I metabolites. The major metabolites were found to be (2S)-14-O-glucuronylpterosin A (M9), (2S)-2-hydroxymethylpterosin E (M14), and (±)-pterosin B (M19). Quantitative HPLC analysis of metabolites, based on similar UV absorption and use of the regression equation of 1, indicated that ∼71% 1 was excreted as metabolites in rat urine.
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, 1, Sec. 1, Jen-Ai Rd., Taipei, 10051, Taiwan, ROC.
authors.forename: Yung-Ping
authors.initials: YP
authors.lastname: Lee
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Hsu
authors.forename: Jaw-Jou
authors.initials: JJ
authors.lastname: Kang
authors.forename: Chien-Kuang
authors.initials: CK
authors.lastname: Chen
authors.forename: Shoei-Sheng
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007189:Indans / Q000378:metabolism* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D012717:Sesquiterpenes / Q000378:metabolism* / Q000652:urine
chemical_list: D007189:Indans; D012717:Sesquiterpenes; C010772:pterosin; C586063:pterosin A