title: Analysis of the metabolites of mesaconitine in rat blood using ultrafast liquid chromatography and electrospray ionization mass spectrometry.
abstract: BACKGROUND
  Mesaconitine is the main active component of genus aconitum plants that are widely used in clinics in China. However, little has been known about the metabolic pathway of mesaconitine.
  
  
  OBJECTIVE
  To explore the metabolites and propose the pathway of mesaconitine.
  
  
  METHODS
  In the present study, mesaconitine (4 mg kg(-1)) was orally administered to male rats. Then, blood samples collected were pretreated using solid-phase extraction technique with C18 cartridges, and analyzed using LC/MS/MS method with electrospray ionization. Both positive ion mode and collision induced dissociation (CID) were used to elucidate the structures of the major metabolites of mesaconitine.
  
  
  RESULTS
  Ten compounds were identified, among which seven were new metabolites, and the metabolic pathway was proposed. The protonated molecular ions of seven new metabolites were at m/z 648, 618, 616, 602, 572, 468, and 542, multistage fragment ions with neutral loss of 28 u (CO), 60 u (CH3COOH), 18 u (H2O), and 32 u (CH3OH). These new metabolites detected firstly in vivo, were named 10-hydroxyl-mesaconitine, hypaconitine, dehydrated mesaconitine 16-O-demethylmesaconitine, 16-O-demethylhypaconitine, and 16-O-demethyl-dehydrated hypaconitine, respectively. Furthermore, the breaking sequence of methoxyl was obtained using quantum chemistry.
  
  
  CONCLUSIONS
  The study proved that the method of solid-phase extraction technique coupled with MS and quantum chemistry can be applied to the analysis of metabolites in plasma quickly and conveniently.
authors.affiliation: Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pharmacology, Peking University, Beijing, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: He
authors.affiliation: Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Liu
keywords: Liquid chromatography-electrospray ion trap-mass spectrometry; mesaconitine; metabolite; quantum chemistry