Metabolite Analysis of Toosendanin by an Ultra-High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry TechniqueReportar como inadecuado




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State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa postcode, Macao





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Abstract Toosendanin is the major bioactive component of Melia toosendan Sieb. et Zucc., which is traditionally used for treatment of abdominal pain and as an insecticide. Previous studies reported that toosendanin possesses hepatotoxicity, but the mechanism remains unknown. Its bioavailability in rats is low, which indicates the hepatotoxicity might be induced by its metabolites. In this connection, in the current study, we examined the metabolites obtained by incubating toosendanin with human live microsomes, and then six of these metabolites M1–M6 were identified for the first time by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry UHPLC-Q-TOF-MS. Further analysis on the MS spectra showed M1, M2, and M3 are oxidative products and M6 is a dehydrogenation product, while M4 and M5 are oxidative and dehydrogenation products of toosendanin. Moreover, their possible structures were deduced from the MS-MS spectral features. Quantitative analysis demonstrated that M1-M5 levels rapidly increased and reached a plateau at 30 min, while M6 rapidly reached a maximal level at 20 min and then decreased slowly afterwards. These findings have provided valuable data not only for understanding the metabolic fate of toosendanin in liver microsomes, but also for elucidating the possible molecular mechanism of its hepatotoxicity. View Full-Text

Keywords: toosendanin; metabolites; human liver microsomes; UHPLC-Q-TOF-MS; MS characterization toosendanin; metabolites; human liver microsomes; UHPLC-Q-TOF-MS; MS characterization





Autor: Jian-Lin Wu, Elaine Lai-Han Leung, Hua Zhou, Liang Liu * and Na Li *

Fuente: http://mdpi.com/



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