STUDIES ON THE METABOLIC PATHWAY OF ACONITINE IN RABBIT AND HUMAN USING ELECTROSPRAY IONIZATION-MASS SPECTROMETRY

Abstract

Aconitine is the main active component of the genus of aconitum plants, which are widely used in clinics in China. To clarify the toxicity and bioactivity of aconitine, the metabolic pathway is an important and key point. After oral administration of aconitine (5 mg · kg⁻¹) to male rabbits, the livers were pretreated by using a solid-phase extraction technique (SPE) with C₁₈ cartridges, and a LC/MS/MS method with electrospray ionization (ESI), positive ion mode, and collision induced dissociation (CID) was used to elucidate the structures of the major metabolites of aconitine. One new metabolite was found; the metabolic pathway was calculated. This result was reproduced in humans who took a medical liquor containing Chuanwu (Aconitum carmichaeli Debx.). In this article, we found two new metabolites; their protonated molecular ions were at m/z 468 and m/z 482, and multistage fragment ions with neutral loss of 18 u (H₂O) and 32 u (CH₃OH). They were detected in vivo, and were labeled dehydra-aconine and dehydra-hypaconine, respectively. The possible metabolic pathway was proposed for the first time.

Keywords:

• aconitine
• electrospray ionization
• HPLC
• in vivo
• mass spectrometry
• metabolic pathway

ACKNOWLEDGMENT

This study was supported by National Natural Science Foundation of China (No. 30901959, No. 39870874).