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  

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

作　　者：邢晗 宁晨 孔德璇 蔡卉 周时雨 任畅 孔颖 程钰洁 陈西敬 XING Han;NING Chen;KONG Dexuan;CAI Hui;ZHOU Shiyu;REN Chang;KONG Ying;CHENG Yujie;CHEN Xijing(Clinical Pharmacokinetics Laboratory,China Pharmaceutical University,Nanjing 211198,Jiangsu,China)

机构地区：[1]中国药科大学基础医学与临床药学学院临床药物代谢动力学研究室

出　　处：《中国临床药理学与治疗学》2019年第8期889-895,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助项目(81473272);江苏省2018年普通高校研究生科研创新计划项目(KYCX18_0802)

摘　　要：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50mg/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50mg/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2~1000ng/mL范围内线性关系良好(R^2>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。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.

关 键 词：GL-V9 抗肿瘤 UPLC-MS/MS 组织分布 排泄 

分 类 号：R284[医药卫生—中药学] R73[医药卫生—中医学]