title: Structural elucidation of koumine metabolites by accurate mass measurements using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry.
abstract: BACKGROUND
  Koumine is one of the major components of total alkaloids from Gelsemium. Koumine possesses a variety of interesting pharmacological effects, including anti-tumor, anti-inflammatory, and anxiolytic activities. It might be a promising lead drug because of its pharmacological activities and mild toxicity. However, little information is available on the metabolism of koumine.
  
  
  METHODS
  A rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight (HPLC/QqTOF) mass spectrometry method was applied to characterize koumine metabolites. Multiple scans of koumine metabolites, which were formed in rat liver S9, were automatically performed simultaneously through auto MS/MS mode acquisition in only a 30-min analysis. The structural elucidation of these metabolites was performed by comparing their changes in accurate molecular masses and product ions with those of the parent drug or metabolites.
  
  
  RESULTS
  As a result, a total of eleven metabolites of koumine were identified, of which nine new metabolites were found. The present results showed that the N-demethylenation, hydrogenation and the oxidation were the three main metabolic pathways of koumine.
  
  
  CONCLUSIONS
  This was the first investigation of in vitro metabolism of koumine in rat liver S9 using a sensitive and specific HPLC/QqTOF-MS method. The possible metabolic pathways of koumine were tentatively proposed based on the structural elucidations of these metabolites. This work may be useful in the in vivo metabolism of koumine in animals and humans. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, 410128, China.|Hunan Engineering Research Center of Veterinary Drug, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, 410128, China.
authors.forename: Sa
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, 410128, China.|Hunan Engineering Research Center of Veterinary Drug, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, 410128, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, 410128, China.|Hunan Engineering Research Center of Veterinary Drug, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, 410128, China.
authors.forename: Zhi-Liang
authors.initials: ZL
authors.lastname: Sun
authors.affiliation: Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, 410128, China.|National and Local Union Engineering Research Center for the Veterinary Herbal Medicine Resources and Initiative, Hunan Agricultural University, Changsha, Hunan, 410128, China.
authors.forename: Zhao-Ying
authors.initials: ZY
authors.lastname: Liu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D026121:Indole Alkaloids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D051381:Rats
chemical_list: D026121:Indole Alkaloids; C515085:koumine