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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 38  |  Page : 101-105

Analysis of the metabolites of mesaconitine in rat blood using ultrafast liquid chromatography and electrospray ionization mass spectrometry


1 Beijing University of Chinese Medicine, Beijing, China
2 Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University, Beijing, China
3 Institute of Clinical Pharmacology, Peking University, Beijing, China

Correspondence Address:
Yonggang Liu
Beijing University of Chinese Medicine, Beijing, 100102
China
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Source of Support: This study was supported by National Natural Science Foundation of China (No. 30901959, No.81102807)., Conflict of Interest: None


DOI: 10.4103/0973-1296.131019

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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. Materials and 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 (CH 3 COOH), 18 u (H 2 O), and 32 u (CH 3 OH). 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. Conclusion: 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.


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