高抗肿瘤活性汉黄芩素衍生物GL-V9在大鼠体内的组织分布和排泄研究

目的:研究抗肿瘤化合物汉黄芩素衍生物GL-V9在大鼠体内的组织分布及排泄特点。方法:组织分布实验中,灌胃给予50 mg/kg的GL-V9混悬液后,根据既定的时间点处死大鼠,采集相应的血浆样品和胃、小肠、肝脏等组织样品,然后以乙酸乙酯作为提取剂对生物样品进行处理后通过UPLC-MS/MS法测定其中的GL-V9含量。排泄实验中,同样灌胃给予大鼠50 mg/kg的GL-V9混悬液,按照既定的时间段收集粪便、尿液和胆汁样品,测定排泄样品中GL-V9的含量,获得相应的累积排泄率。结果:各组织和排泄样品中GL-V9在2～1 000 ng/mL范围内线性关系良好（R2＞0.99）。组织分布实验结果显示,灌胃给药后GL-V9由胃肠道逐渐向肝脏、肺、肾组织分布,在脑、心和血浆中的含量较低。排泄实验表明,口服给药后,粪便中GL-V9排泄量最高,累积排泄率达（75.41±41.77）%。结论:GL-V9在大鼠各组织中的分布较为广泛,尤其是胃肠道、肝脏、肺和肾脏组织,而粪便则是GL-V9在大鼠体内的主要排泄途径。

Tissue distribution and excretion study of GL-V9 in rats,a wogonin derivative with significant antitumor activity

AIM: To study the tissue distribution and excretion characteristics of GL-V9, an antitumor derivative of wogonin, in rats. METHODS: In tissue distribution study, blood and tissue samples of rats were collected after oral administration of GL-V9 (50 mg/kg), including stomach, small intestine, liver, and so on. Samples were processed with ethyl acetate and then analyzed by UPLC-MS/MS for quantification. In excretion study, rats were given GL-V9 by oral gavage at 50 mg/kg. Feces, urine and bile samples were gathered and determined using UPLC-MS/MS to investigate the excretion characteristics of GL-V9. RESULTS:The results indicated that the UPLC-MS/MS method for GL-V9 showed a good linearity over the linear range of 2-1 000 ng/mL. Tissue distribution results showed that the distribution trend of GL-V9 was from gastrointestinal tract to liver, lung and kidney tissues after oral administration, while the concentration levels of GL-V9 in brain, heart and blood were very low. The results of excretion experiments showed that the amount of GL-V9 in feces was the highest and the cumulative excretion percentage of feces was (75.41±41.77)%. CONCLUSION: GL-V9 can be widely distributed in various tissues of rats, especially in gastrointestinal tract, liver, lung and kidney tissues. Fecal excretion is the main excretion pathway of GL-V9 in rats.