title: The profiling of the metabolites of hirsutine in rat by ultra-high performance liquid chromatography coupled with linear ion trap Orbitrap mass spectrometry: An improved strategy for the systematic screening and identification of metabolites in multi-samples in vivo.
abstract: Drug metabolites identification and construction of metabolic profile are meaningful work for the drug discovery and development. The great challenge during this process is the work of the structural clarification of possible metabolites in the complicated biological matrix, which often resulting in a huge amount data sets, especially in multi-samples in vivo. Analyzing these complex data manually is time-consuming and laborious. The object of this study was to develop a practical strategy for screening and identifying of metabolites from multiple biological samples efficiently. Using hirsutine (HTI), an active components of Uncaria rhynchophylla (Gouteng in Chinese) as a model and its plasma, urine, bile, feces and various tissues were analyzed with data processing software (Metwork), data mining tool (Progenesis QI), and HR-MSndata by ultra-high performance liquid chromatography/linear ion trap-Orbitrap mass spectrometry (U-HPLC/LTQ-Orbitrap-MS). A total of 67 metabolites of HTI in rat biological samples were tentatively identified with established library, and to our knowledge most of which were reported for the first time. The possible metabolic pathways were subsequently proposed, hydroxylation, dehydrogenation, oxidation, N-oxidation, hydrolysis, reduction and glucuronide conjugation were mainly involved according to metabolic profile. The result proved application of this improved strategy was efficient, rapid, and reliable for metabolic profiling of components in multiple biological samples and could significantly expand our understanding of metabolic situation of TCM in vivo.
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China; School of Chemical and Biological Engineering, Nantong Vocational University, Nantong 226007, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qi
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Hou
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Qirui
authors.initials: Q
authors.lastname: Bi
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Deng
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Shi
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Feng
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China.
authors.forename: Zijin
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: wanyingwu@simm.ac.cn.
authors.forename: Wanying
authors.initials: W
authors.lastname: Wu
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: daguo@simm.ac.cn.
authors.forename: Dean
authors.initials: D
authors.lastname: Guo
mesh_terms: D000470:Alkaloids / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods*; D032070:Uncaria
chemical_list: D000470:Alkaloids; D004365:Drugs, Chinese Herbal; C038369:hirsutine
keywords: Hirsutine; Metabolic profile; Metabolites systematic screening; Multi-samples; UHPLC/LTQ-Orbitrap-MS; Uncaria rhynchophylla