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引用本文:   丛宇婷, 胡良海, 叶明亮, 顾景凯, 邹汉法. 基于质谱技术的贝伐珠单抗及其糖基化修饰的表征、定量与药代动力学分析. 分析化学, 2017, 45(11): 1678-1685. doi:  10.11895/j.issn.0253-3820.170170 [复制]

Citation:   CONG Yu-Ting, HU Liang-Hai, YE Ming-Liang, GU Jing-Kai, ZOU Han-Fa. Characterization, Quantification and Pharmacokinetic Analysis of Bevacizumab and Its Glycosylation by Mass Spectrometry. Chinese Journal of Analytical Chemistry, 2017, 45(11): 1678-1685. doi: 10.11895/j.issn.0253-3820.170170 [复制]

基于质谱技术的贝伐珠单抗及其糖基化修饰的表征、定量与药代动力学分析

通讯作者:  胡良海, lianghaihu@jlu.edu.cn

收稿日期: 2017-03-20

接受日期: 2017-09-07

出版日期: 2017-11-20

基金项目: 本文系国家自然科学基金项目(No.81373374)资助

Characterization, Quantification and Pharmacokinetic Analysis of Bevacizumab and Its Glycosylation by Mass Spectrometry

Corresponding author:  HU Liang-Hai, lianghaihu@jlu.edu.cn

Received Date:  2017-03-20

Accepted Date:  2017-09-07

Published Date:  2017-11-20

Fund Project:  This work was supported by the National Natural Science Foundation of China (No. 81373374)

利用基质辅助激光解析电离飞行时间质谱技术、SDS-聚丙烯酰胺凝胶电泳技术以及Shot-gun蛋白质组学策略对贝伐珠单克隆抗体药物及其糖基化修饰进行了全面表征,共发现17种糖型并确定了特征肽段序列。利用液相色谱-串联质谱联用技术,采用平行反应检测模式,通过测定单抗水解后产生的特征肽段,实现了对大鼠血浆样品中单抗药物含量的绝对定量分析,获得不同给药计量下的贝伐珠单抗的药物浓度-时间曲线,同时实现了对单抗糖基化修饰各糖型的相对定量分析。本实验首先建立标准工作曲线,对大鼠血浆样品中的贝伐珠单抗进行定量分析,在线性范围内,相关系数R2=0.998,定量限为66 fmol,线性关系良好。对大鼠血浆样品的测定结果表明,高、低计量给药的贝伐珠单抗药物浓度-时间曲线趋势基本一致,浓度均为直接下降,与理论趋势相符。但是大多数糖型呈现浓度先上升的现象,之后的代谢情况因糖型差异而有所不同。

关键词:   贝伐珠单抗, 糖基化修饰, 液相色谱-串联质谱联用, 平行反应监测, 药代动力学
Key words:   Bevacizumab, Glycosylation, Liquid chromatography-tandem mass spectrometry, Parallel reaction monitoring, Pharmacokinetics
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目录

基于质谱技术的贝伐珠单抗及其糖基化修饰的表征、定量与药代动力学分析

丛宇婷, 胡良海, 叶明亮, 顾景凯, 邹汉法

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