title: Profiling and identification of (-)-epicatechin metabolites in rats using ultra-high performance liquid chromatography coupled with linear trap-Orbitrap mass spectrometer.
abstract: (-)-Epicatechin (EC), an optical antipode of (+)-catechin (C), possesses many potential significant health benefits. However, the in vivo metabolic pathway of EC has not been clarified yet. In this study, an efficient strategy based on ultra-high performance liquid chromatography coupled with a linear ion trap-Orbitrap mass spectrometer was developed to profile and characterize EC metabolites in rat urine, faeces, plasma, and various tissues. Meanwhile, post-acquisition data-mining methods including high-resolution extracted ion chromatogram (HREIC), multiple mass defect filters (MMDFs), and diagnostic product ions (DPIs) were utilized to screen and identify EC metabolites from HR-ESI-MS1to ESI-MSnstage. Finally, a total of 67 metabolites (including parent drug) were tentatively identified based on standard substances, chromatographic retention times, accurate mass measurement, and relevant drug biotransformation knowledge. The results demonstrated that EC underwent multiple in vivo metabolic reactions including methylation, dehydration, hydrogenation, glucosylation, sulfonation, glucuronidation, ring-cleavage, and their composite reactions. Among them, methylation, dehydration, glucosylation, and their composite reactions were observed only occurring on EC when compared with C. Meanwhile, the distribution of these detected metabolites in various tissues including heart, liver, spleen, lung, kidney, and brain were respectively studied. The results demonstrated that liver and kidney were the most important organs for EC and its metabolites elimination. In conclusion, the newly discovered EC metabolites significantly expanded the understanding on its pharmacological effects and built the foundation for further toxicity and safety studies. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No. 6, Wang Jing Zhong Huan Nang Lu South Road, Wangjing, Chaoyang District, Beijing, 100102, China.
authors.forename: Zhanpeng
authors.identifier: http://orcid.org/0000-0002-1576-7867
authors.initials: Z
authors.lastname: Shang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No. 6, Wang Jing Zhong Huan Nang Lu South Road, Wangjing, Chaoyang District, Beijing, 100102, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, No. 6, Wang Jing Zhong Huan Nang Lu South Road, Wangjing, Chaoyang District, Beijing, 100102, China.
authors.forename: Shengyun
authors.initials: S
authors.lastname: Dai
authors.affiliation: Library of Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China.
authors.forename: Jianqiu
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Herbal Medicine, School of Basic Medical Sciences, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D002392:Catechin / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057225:Data Mining / Q000379:methods; D020719:Glucuronides / Q000378:metabolism; D006900:Hydroxylation; D007004:Hypoglycemic Agents / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008297:Male; D053858:Metabolic Networks and Pathways; D008745:Methylation; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000975:Antioxidants; D020719:Glucuronides; D007004:Hypoglycemic Agents; D002392:Catechin
keywords: (−)-epicatechin; mass spectrometer; metabolites; post-acquisition data-mining methods; ultra-high performance liquid chromatography coupled with a linear trap-Orbitrap