抗肿瘤新化合物LS-177在不同种属中血浆蛋白结合率的测定  

Determination of plasma protein binding rate of a novel anticancer LS-177 in several species

作　　者：张伦会 曾敏 杜美容 陈晓辉[2] 鞠平 ZHANG Lun-hui;ZENG Min;DU Mei-rong;CHEN Xiao-hui;JU Ping(Department of Pharmacy,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,China;Shenyang Pharmaceutical University,Shenyang 110016,China;Leadingpharm Medical Technology Co.,Ltd.,Beijing 100000,China)

机构地区：[1]西南医科大学附属医院药学部,泸州646000 [2]沈阳药科大学药学院,沈阳110016 [3]北京新领先医药科技发展有限公司,北京100000

出　　处：《中国新药杂志》2019年第2期221-228,共8页Chinese Journal of New Drugs

摘　　要：目的:建立血浆中LS-177的分析方法,测定LS-177与大鼠、比格犬和人的血浆蛋白结合率。方法:采用平衡透析法模拟LS-177在体内与血浆蛋白的结合过程,采用UPLC-MS/MS方法对透析外液和内液中LS-177的含量进行测定,计算LS-177与大鼠、比格犬和人的血浆蛋白结合率。结果:LS-177低、中、高(25,50和100 ng·m L-1) 3个浓度的大鼠血浆蛋白结合率分别是(81. 2±5. 2)%,(77. 2±6. 2)%,(79. 8±5. 2)%;比格犬血浆蛋白结合率分别是(84. 2±2. 7)%,(82. 5±3. 1)%,(84. 1±3. 9)%;人血浆蛋白结合率分别是(84. 0±3. 4)%,(81. 7±4. 0)%,(80. 5±3. 4)%。结论:建立的LS-177蛋白结合率测定方法简便、稳定、可靠,LS-177血浆蛋白结合率不具有明显的浓度依赖性和种属差异。Objective:To establisha method for the analysis of LS-177 in plasma and determination the plasma protein binding rate of LS-177 and different species plasma protein (Rat,Beagle and human).Methods: Equilibrium dialysis method was utilized to imitate the binding process between LS-177 and different species plasma protein.The concentration of LS-177 in and out of the dialysis membrane was determined by UPLC-MS/MS and the plasma protein binding rates of LS-177 and different species plasma protein (Rat,Beagle and human)were calculated. Results:Plasma protein binding rates of LS-177 at three various concentrations (25,50 and 100 ng·mL^-1)were (81.2±5.2)%,(77.2±6.2)%,(79.8 ±5.2)%in rat plasma;(84.2±2.7)%,(82.5±3.1)%,(84.1±3.9)%in beagle plasma and (84.0±3.4)%,(81.7±4.0)%,(80.5±3.4)%in human plasma,respectively. Conclusion:This method for determining plasma protein binding rates of LS-177 was simple,stable and reliable. The plasma protein binding rate of LS-177 has no significance concentration dependent and species differences.

关 键 词：LS-177 血浆蛋白结合率 平衡透析法 UPLC-MS/MS 

分 类 号：R965[医药卫生—药理学]