title: Profiling and identification of metabolites of isorhynchophylline in rats by ultra high performance liquid chromatography and linear ion trap Orbitrap mass spectrometry.
abstract: The searching of potentially bioactive metabolites in the biological body is an interesting and meaningful work for the drug study. However, the structural clarification of possible metabolites is one of the most challenging tasks in drug metabolism studies because of the variety of metabolic reactions and complexity of metabolites in vivo. Here, an ultra high performance liquid chromatography/linear ion trap-Orbitrap mass spectrometry (U-HPLC/LTQ-Orbitrap-MS) with combination of data post-processing techniques, including extracted ion chromatogram (EIC) and multiple mass defect filters (MMDF), was established for profiling and identification of metabolites of isorhynchophylline (IR) in vivo and in vitro, and the possible metabolic pathways were subsequently proposed after the oral dose of 20mg/kg; A total of 47 metabolites of IR were tentatively identified, including 47, 21, 18, and 25 metabolites in rat urine, plasma, liver and rat liver microsomes (RLM) samples, respectively. To our knowledge, most of them were reported for the first time. Seven metabolic pathways, including dehydrogenation, oxidation, hydrolysis, reduction, demethylation, hydroxylation and glucuronide conjugation were involved in the metabolism. Among them, dehydrogenation, hydrolysis, hydroxylation and oxidation were considered as the main metabolic pathway of metabolism according to metabolic profile of in vivo and in vitro. The relative percentage of each metabolite and main metabolite types were also determined to better understand the metabolic behavior of IR in rats. The newly discovered IR metabolites significantly expanded our understanding and were going to be greatly helpful for the further pharmacokinetic study of IR in vivo.
authors: 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: Jianwei
authors: J
authors: Wang
authors: 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: Peng
authors: P
authors: Qi
authors: 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: Jinjun
authors: J
authors: Hou
authors: 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: Yao
authors: Y
authors: Shen
authors: 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: Bingpeng
authors: B
authors: Yan
authors: 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: Qirui
authors: Q
authors: Bi
authors: 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: RuiHong
authors: R
authors: Feng
authors: 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: Xiaojian
authors: X
authors: Shi
authors: 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: Min
authors: M
authors: Yang
authors: 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: Wanying
authors: W
authors: Wu
authors: 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: De-An
authors: DA
authors: Guo
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D026121:Indole Alkaloids / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism; D000078183:Oxindoles; D051381:Rats; D017208:Rats, Wistar
chemical_list: D026121:Indole Alkaloids; D000078183:Oxindoles; C052714:rhyncophylline
keywords: Isorhynchophyllin; Metabolic profile; Metabolites; UHPLC/LTQ-Orbitrap-MS