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Detection and Structural Characterization of Nucleophiles Trapped Reactive Metabolites of Limonin Using Liquid Chromatography-Mass Spectrometry
Joint Authors
Deng, Yujie
Wang, Ping
Fu, Yudong
Xu, Shumin
Yang, Nailong
Li, Chengqian
Yu, Qing
Source
Journal of Analytical Methods in Chemistry
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-04-17
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Limonin (LIM), a furan-containing limonoid, is one of the most abundant components of Dictamnus dasycarpus Turcz.
Recent studies demonstrated that LIM has great potential for inhibiting the activity of drug-metabolizing enzymes.
However, the mechanisms of LIM-induced enzyme inactivation processes remain unexplored.
The main objective of this study was to identify the reactive metabolites of LIM using liquid chromatography-mass spectrometry.
Three nucleophiles, glutathione (GSH), N-acetyl cysteine (NAC), and N-acetyl lysine (NAL), were used to trap the reactive metabolites of LIM in in vitro and in vivo models.
Two different types of mass spectrometry, a hybrid quadrupole time-of-flight (Q-TOF) mass spectrometry and a LTQ velos Pro ion trap mass spectrometry, were employed to acquire structural information of nucleophile adducts of LIM.
In total, six nucleophile adducts of LIM (M1–M6) with their isomers were identified; among them, M1 was a GSH and NAL conjugate of LIM, M2–M4 were glutathione adducts of LIM, M5 was a NAC and NAL conjugate of LIM, and M6 was a NAC adduct of LIM.
Additionally, CYP3A4 was found to be the key enzyme responsible for the bioactivation of limonin.
This metabolism study largely facilitates the understanding of mechanisms of limonin-induced enzyme inactivation processes.
American Psychological Association (APA)
Deng, Yujie& Fu, Yudong& Xu, Shumin& Wang, Ping& Yang, Nailong& Li, Chengqian…[et al.]. 2018. Detection and Structural Characterization of Nucleophiles Trapped Reactive Metabolites of Limonin Using Liquid Chromatography-Mass Spectrometry. Journal of Analytical Methods in Chemistry،Vol. 2018, no. 2018, pp.1-9.
https://search.emarefa.net/detail/BIM-1176316
Modern Language Association (MLA)
Deng, Yujie…[et al.]. Detection and Structural Characterization of Nucleophiles Trapped Reactive Metabolites of Limonin Using Liquid Chromatography-Mass Spectrometry. Journal of Analytical Methods in Chemistry No. 2018 (2018), pp.1-9.
https://search.emarefa.net/detail/BIM-1176316
American Medical Association (AMA)
Deng, Yujie& Fu, Yudong& Xu, Shumin& Wang, Ping& Yang, Nailong& Li, Chengqian…[et al.]. Detection and Structural Characterization of Nucleophiles Trapped Reactive Metabolites of Limonin Using Liquid Chromatography-Mass Spectrometry. Journal of Analytical Methods in Chemistry. 2018. Vol. 2018, no. 2018, pp.1-9.
https://search.emarefa.net/detail/BIM-1176316
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1176316