朝藿定B在大鼠体内的药物代谢研究

In vivo Metabolism Study of Epimedin B

目的探讨朝藿定B在大鼠体内的代谢产物及转化途径。方法选择SD大鼠12只,分为2组,肌肉注射组和口服给药组,收集给药前和给药后0~24 h尿样和粪便样品,采用高效液相色谱-串联线性离子阱静电场轨道阱质谱仪(LC-LTQ Orbitrap MSn)检测。结果通过比较给药前后各组总离子流色谱图,对尿和粪便中推测的代谢物和标准物质的出峰时间及相关化合物的多级串联质谱数据进行了分析,结果在粪便中发现了14种药物代谢产物,系统分析了这些代谢产物的代谢转化规律及可能的结构。而尿液中代谢产物的数量和含量远低于粪便,最终在尿液中找到的4种微量代谢产物,其在粪便中均有发现。结论朝藿定B在大鼠体内的主要转化途径为结合、水解、氧化、加成及脱甲基反应等。

Objective To study the metabolic pathways of Epimedin B in rats. Methods Twelve Sprague Dawley rats were classed into 2 groups, corresponding to an intermuscular administration and an oral administration group respectively. Rat feces and urine samples were collected before dose and at 24 h after administration. All samples were pretreated and analyzed by LC-LTQ Orbitrap MSn. Results By comparison between the total ion chromatograms of samples after administration with the samples before dose, the possible metabolites in the samples of drug-treated group were preliminarily screened and further assigned by multistage product ion scanning and comparison of retention time with reference substances. As a result, fourteen metabolites were identified in rat feces and four metabolites were identified in rats urine. The possible main metabolic pathway and potential structures were elucidated. Conclusion Glycosylation, hydrolysis, oxidation, addition and demethylation were found to be the major steps in metabolic pathway of Epimedin B in rats.