title: Metabolic profile of 5-hydroxy-4-methoxycanthin-6-one, a typical canthinone alkaloid, in rats determined by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry together with multiple data processing techniques.
abstract: Picrasma quassioides (D. Don) Benn. is a traditional Chinese medicine used clinically to treat gastrointestinal disorders and as a vermifuge. 5-Hydroxy-4-methoxycanthin-6-one (CAN), a major canthinone alkaloid found in P. quassioides, has significant pharmacological activities. In the present study, a method using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry together with multiple data processing techniques, including extracted ion chromatogram, multiple mass defect filter, precursor/product ion scanning and neutral loss scanning was developed to screen and characterize the phase I and II metabolites of CAN in plasma, bile, urine and feces of rats after a single oral dose of 20mg/kg. A total of 17 metabolites were tentatively or conclusively identified. Pathways for the metabolism of CAN have been proposed, and include hydroxylation, N-decarbonylation, methylation, oxidation and sequential conjugation. A previously unknown metabolically active site at the C4-C6 position and a novel N-decarbonylation-oxidation metabolic pathway for the prototypical canthinone alkaloid, CAN, were discovered. Our results provide valuable information about the in vivo metabolism of CAN that can also be used as a comprehensive guide for the biotransformation of other canthinone alkaloids.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Jueyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China. Electronic address: fengsunlight@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory on Protein Chemistry and Structural Biology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liuwenyuan8506@163.com.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000032:analysis* / Q000378:metabolism*; D000818:Animals; D002243:Carbolines / Q000032:analysis* / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D001330:Electronic Data Processing / Q000379:methods*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D032270:Picrasma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000470:Alkaloids; D002243:Carbolines; C468517:5-methoxycanthin-6-one
keywords: Canthinone alkaloids; Liquid chromatography-quadrupole time-of-flight tandem mass spectrometry; Metabolites; Multiple mass defect filter; Picrasma quassioides (D. Don) Benn.