喘可治注射液在大鼠体内的药物代谢研究

In vivo study of Chuankezhi metabolism in rat

探讨喘可治注射液在大鼠体内的代谢转化。选择SD大鼠12只,分为两组,分别为对照组和肌肉注射给药组,收集给药后0~24 h、24~48 h粪便和尿液样品,给药后0.5、2和24 h血样,甲醇超声提取,沉淀蛋白,高效液相色谱-串联线性离子阱静电场轨道阱质谱仪检测。通过比较给药组和对照组的总离子流色谱图,对粪便、尿液以及血浆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,结果在大鼠尿液中未检测到相关代谢产物;在大鼠给药后0.5 h血样中可检测到在喘可治注射液中含量较大的原形药物,如朝藿定C和淫羊藿苷,但未能检测到其他原形药物和相关代谢产物,而大鼠给药后2和4 h血样中则均未能检测到原形药物和相关代谢产物;在大鼠粪便中发现了12种黄酮类代谢产物,系统分析了这些代谢产物的代谢转化规律及可能结构。大鼠体内喘可治注射液所含化学成分的主要代谢转化途径为脱糖、脱水、氧化、甲基化和异构化代谢反应等。

To study the metabolic products of main compounds of Chuankezhi injection in rat, 12 Sprague Dawley rats were classed into 2 groups, a blank control group and an intermuscular administration group, respectively. Rat feces and urine samples were collected from 0-24 h and 24-48 h after administration. All the samples were ultrasonically treated with methanol and then analyzed using LC-LTQ Orbitrap MSn. By comparison with the total ion chromatogram of samples from the blank control group, the metabolites in the samples of drug-treated group were screened. These metabolites were further analyzed by multistage product ion scanning and comparison of retention time with reference substances. As a result, a total of 12 flavonoid metabolites were tentatively identified from the rat feces and no metabolite was discovered in the rat urine. Epimedin C and icariin were detected in the rat blood samples after 30 min of administration, but their metabolites and other original flavones were not detected. Furthermore, no original flavones and their metabolites were detected in rat blood samples after 2 and 4 h of administration. The potential metabolism paths were further characterized and the principal in vivo transformation of flavones from Chuankezhi injection were deglycosylation, dehydration, methylation, oxidation and isomerization in rats.