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中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (8): 889-895.doi: 10.12092/j.issn.1009-2501.2019.08.007

• 基础研究 • 上一篇    下一篇

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

邢 晗,宁 晨,孔德璇,蔡 卉,周时雨,任 畅,孔 颖,程钰洁,陈西敬   

  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,南京 211198,江苏
  • 收稿日期:2019-03-07 修回日期:2019-06-03 出版日期:2019-08-26 发布日期:2019-08-30
  • 通讯作者: 陈西敬,男,博士,教授,博导,研究方向:药物代谢动力学。 Tel:025-86185379 E-mail:chenxj-lab@hotmail.com
  • 作者简介:邢晗,女,博士研究生,研究方向:药物代谢动力学。 Tel:15851838760 E-mail:xinghankf@126.com
  • 基金资助:

    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)

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

XING Han, NING Chen, KONG Dexuan, CAI Hui, ZHOU Shiyu, REN Chang, KONG Ying, CHENG Yujie, CHEN Xijing   

  1. Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing 211198, Jiangsu, China
  • Received:2019-03-07 Revised:2019-06-03 Online:2019-08-26 Published:2019-08-30

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。

关键词: GL-V9, 抗肿瘤, UPLC-MS/MS, 组织分布, 排泄

Abstract:

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.

Key words: GL-V9, antitumor, UPLC-MS/MS, tissue distribution, excretion

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