Simultaneous determination of resibufogenin and its major metabolite 3-epi-resibufogenin in rat plasma by HPLC coupled with tandem mass spectrometry

摘要

ChanSu, also called toad venom, is one of important traditional Chinese medicine (TCM) originated from the skin secretions of Bufo bufo gargarizans Cantor and B. melsanostictus Schneider [1-2]. Resibufogenin (RBG) was a major bufadienolide with the content of 1-6% in Chansu. And it had strong cytotoxic activities against human myeloid leukemia, prostate cancer and human hepatoma cells with 1C5O values of 1-10 nmol/L[3-5]. However, as a cardioactive steroid with a-pyrone ring, RBG can adversely affect the myocardium to produce the most life-threatening toxicity includes ventricular ectopy and hyperkalemia with a narrow therapeutic index [6-7], So it is necessary to investigate the pharmacokinetic behaviors of RBG and its metabolites in vivo to define the pharmacokinetic and safety profiles, and establish optimal doses for maximal efficacy as preclinical and clinical trials.