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

• Published in: Journal of pharmaceutical and biomedical analysis 2016-09, Vol.129, p.60-69
• Main Authors: Shi, Yuanyuan, Xia, Yuanyuan, Wang, Jueyu, He, Jinfeng, Feng, Feng, Liu, Wenyuan
• Format: Article
• Language: English
• Subjects: Alkaloids - analysis; Alkaloids - metabolism; Animals; Canthinone alkaloids; Carbolines - analysis; Carbolines - metabolism; Chromatography, Liquid - methods; Electronic Data Processing - methods; Liquid chromatography-quadrupole time-of-flight tandem mass spectrometry; Male; Metabolites; Metabolomics - methods; Multiple mass defect filter; Picrasma - metabolism; Picrasma quassioides (D. Don) Benn; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry - methods
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2016.06.047

[Display omitted] •An LC-Q-TOF-MS method coupled with multiple data processing techniques was developed.•The method was applied for profile metabolites of 5-hydroxy-4-methoxycanthin-6-one.•A total of 17 metabolites were observed and 3 of them were confirmed.•The metabolic pathways and the fragmentation patterns of metabolites were summarized.•This present a valuable supplement for the biotransformation of canthinone-alkaloids. 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.