Molecules 2013, 18(10), 12144-12153; doi:10.3390/molecules181012144
Article

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

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
* Authors to whom correspondence should be addressed.
Received: 29 July 2013; in revised form: 25 September 2013 / Accepted: 26 September 2013 / Published: 30 September 2013
(This article belongs to the Section Metabolites)
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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.
Keywords: toosendanin; metabolites; human liver microsomes; UHPLC-Q-TOF/MS; MS characterization

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MDPI and ACS Style

Wu, J.-L.; Leung, E.L.-H.; Zhou, H.; Liu, L.; Li, N. Metabolite Analysis of Toosendanin by an Ultra-High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry Technique. Molecules 2013, 18, 12144-12153.

AMA Style

Wu J-L, Leung EL-H, Zhou H, Liu L, Li N. Metabolite Analysis of Toosendanin by an Ultra-High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry Technique. Molecules. 2013; 18(10):12144-12153.

Chicago/Turabian Style

Wu, Jian-Lin; Leung, Elaine L.-H.; Zhou, Hua; Liu, Liang; Li, Na. 2013. "Metabolite Analysis of Toosendanin by an Ultra-High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry Technique." Molecules 18, no. 10: 12144-12153.

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