高三尖杉酯碱在大鼠及兔肝微粒体的代谢研究

采用动物肝微粒体体外代谢法对高三尖杉酯碱进行了代谢转化的研究。应用梯度洗脱—反相HPLC结合二极管陈列检测器对体外代谢体系进行了分析。判定在体外代谢体系中,高三尖杉酯碱主要产生一个代谢产物。用HPLC法制备出一定量代谢物纯品,经光谱分析及与化学制备的对照品相比较,推定其代谢物结构为:2′-羟基-2′(α-乙酸)-6′-甲基-6′-羟基-庚酰三尖杉碱。

THE METABOLISM OF HOMOHARRINGTONINE BY LIVER MICROSOMES OF RATS AND RABBITS

In this paper, the metabolism of homoharringtonine has been studied in vitro with liver microsomes from rats and rabbits. A method of HPLC-DAD (photodiode array detector) with gradient elution was developed for screening the metabolites from the microsomal incubation system. Only one main metabolite, whose formation was independent of NADPH and NADH, was found. The metabolite was extracted and purified with preparative HPLC technique. Its chemical structure was identified as 2'-hydroxy-2'(alpha-acetic acid)-6'-hydroxy-6'-methyl-heptanoyl cephalotaxine by UV, IR, NMR, MS analysis, and confirmed further by comparison with the authentic compound, the spectra and chromatographic behavior were all the same. The rates of the metabolite formation was markedly increased in the phenobarbital pretreated liver microsome system.