新型抗脑卒中化合物TID-101自微乳制剂大鼠体内生物利用度研究  

Bioavailability study of self-microemulsifying drug delivery system of a novel anti-stroke compound TID-101 in rats

作　　者：高广宇[1] 梅丹宇 喻芳邻[1] 余惟平 王汝涛 龚伟[1] 梅兴国[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]西安力邦肇新生物科技有限公司,西安710077

出　　处：《国际药学研究杂志》2016年第4期731-735,共5页Journal of International Pharmaceutical Research

基　　金：国家科技重大专项综合性新药研究开发大平台(2012ZX09301003-001-009)

摘　　要：目的建立测定大鼠血浆中防治缺血性脑卒中化合物TID-101的LC-MS/MS方法,并研究其自微乳制剂大鼠体内生物利用度及药代动力学特征。方法血浆样品用甲醇沉淀蛋白处理,以乙腈-水为流动相,采用ESI源以多反应监测方式进行负离子检测,用于定量分析的离子反应为m/z 353.4→323.2（TID-101）和433.4→353.4（醋酸地塞米松,内标）。将建立的方法应用于大鼠口服TID-101自微乳的生物利用度及药代动力学研究。结果 TID-101在10~95 000 ng/ml内呈良好的线性关系（r=0.999 8）,日内、日间精密度（RSD）均〈15%,回收率在83.4%~87.0%之间。应用此法测试大鼠静脉注射TID-101脂肪乳和口服原料药及自微乳制剂后的血药浓度,计算出原料药混悬液和自微乳的口服绝对生物利用度分别为2.8%和14.9%。结论本法操作简单、准确、灵敏度高,可用于TID-101大鼠体内药动学研究;自乳化释药系统能有效提高TID-101大鼠口服生物利用度。Objective To establish and validate a LC-MS/MS method for quantitative analysis of a new anti-stroke compound TID-101 in rat plasma and to study the pharmacokinetics and bioavailability of TID-101 self-（micro）emulsified drug delivery system（SMEDDS）. Methods The plasma samples were treated with methanol for precipitating protein. The chromatographic separation was achieved with a acetonitrile- water mobile phase. Detection of TID- 101 and the internal standard（IS）dexamethasone acetate was achieved by electrospray ionization（ESI）source in the negative ion mode at m/z 353.4→323.2 and m/z 433.4→353.4. The method was applied for pharmacokinetics study of TID-101 between SMEDDS in rats. Results The method was linear over TID-101 concentration range from 10-95 000 ng/ml with the correlation coefficients（r）of 0.9998. The intra-run and inter-run relative standard deviations（RSD）were less than 15% and the average absolute recovery values were 83.4-87.0%. The validated method was applied to a pharmacokinetic study in rats after intravenous administration of TID-101 fat emulsion injection and oral administration of TID-101 suspension and SMEDDS. The bioavailability of TID-101 API and SMEDDS was 2.8% and 14.9%,respectively. Conclusion The analysis method is simple,accurate,and sensitive for assaying the in vivo pharmacokinetic study of TID-101 in rats. SMEDDS could effectively enhance the oral bioavailability of TID-101.

关 键 词：脑卒中 液相色谱-串联质谱 自乳化释药系统 药代动力学 生物利用度 

分 类 号：R965[医药卫生—药理学]