摘要
目的:建立一种通用、简便的LC-MS/MS分析方法,测定给予阿柏西普后大鼠血浆中产生的血管内皮生长因子(vascular endothelial growth factor,VEGF)-阿柏西普复合物的浓度,研究该复合物在大鼠体内的药动学行为。方法:血浆样品前处理采用了Protein A/G磁珠捕获,通过胰蛋白酶进行特异性酶切,选取了来自VEGF-A的特征肽的稳定、可靠离子对(m/z 451.2→531.3)进行定量分析。结果:建立的Protein A/G磁珠捕获结合LC-MS/MS法测定大鼠血浆中VEGF-阿柏西普复合物在0.05~5μg·mL^(-1)浓度范围内线性关系良好,最低定量限为0.05μg·mL^(-1),经验证符合生物样本分析的要求。大鼠尾静脉注射阿柏西普(10 mg·kg^(-1))后体内生成的VEGF-阿柏西普复合物的主要药动学参数:Tmax为(240±0)h,Cmax为(2.95±0.55)μg·mL^(-1),AUC0-∞为(788.33±134.13)h·μg·mL^(-1)。结论:本方法适用于给予阿柏西普后大鼠体内产生的VEGF-阿柏西普复合物的血药浓度检测和药动学评价研究。
Objective:To establish a universal and simple LC-MS/MS method for determining the concentration of VEGF-VEGF trap complex produced in rat plasma after aflibercept administration,and study the pharmacokinetic behavior of the complex in rats.Methods:Plasma samples were pretreated with Protein A/G magnetic bead capture and specifically digested by trypsin.A stable and reliable ion pair(m/z 451.2→531.3)from surrogate peptide of VEGF-A of VEGF-VEGF trap was selected for quantification.Results:The established Protein A/G magnetic bead capture combined with LC-MS/MS method was linear in the range of 0.05~5μg·mL^(-1)(r>0.9996),and the lowest limit of quantification was 0.05μg·mL^(-1),verified to meet the requirements of biological sample analysis.The main pharmacokinetic parameters of VEGF-VEGF trap produced in rats after intravenous injection of aflibercept(10 mg·kg^(-1))were Tmax(240±0)h,Cmax(2.95±0.55)μg·mL^(-1),and AUC0-∞(788.33±134.13)h·μg·mL^(-1).Conclusion:This method is suitable for the detection of VEGF-VEGF trap concentration and pharmacokinetic evaluation in rat plasma after administration of aflibercept.
作者
孔琳琳
余飞
刘欢
沙春洁
刘万卉
KONG Lin-lin;YU Fei;LIU Huan;SHA Chun-jie;LIU Wan-hui(School of Pharmacy,Yantai University,Yantai 264005,China;Luye Pharmaceutical Group Co.,Ltd.,Yantai 264670,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2020年第24期2846-2851,共6页
Chinese Journal of New Drugs
基金
国家自然科学基金资助项目(81773679)
烟台大学研究生科技创新基金资助项目(YDZD1917)。
