治疗性单克隆抗体修饰变异体的液质联用分析技术进展  

Advances in LC-MS Analysis of Therapeutic Monoclonal Antibody Modification Variants

作　　者：叶沛均 左成意 刘振虎 廖玉玲 江正瑾 王启钦 YE Pei-jun;ZUO Cheng-yi;LIU Zhen-hu;LIAO Yu-ling;JIANG Zheng-jin;WANG Qi-qin(Institute of Pharmaceutical Analysis,College of Pharmacy,Jinan University,Guangzhou 511436,China)

机构地区：[1]暨南大学药学院药物分析研究中心,广东广州511436

出　　处：《化学试剂》2024年第12期1-12,共12页Chemical Reagents

基　　金：暨南大学中央高校基本科研业务费-JG计划项目(21623407);国家自然科学基金面上项目(82173773);广东省药品监督管理局科技创新项目(2023TDZ11);广东省自然科学基金-省企联合基金面上项目(2021A1515220099);广州市科技计划“续航”项目(2024A04J9919)。

摘　　要：治疗性单克隆抗体(mAbs)因具有靶向性高、药效作用强等优点而广泛应用于恶性肿瘤和自身免疫性疾病的高效治疗,成为全球新药研发热点。由于抗体药物自身结构复杂,尤其在生产、储存等过程甚至在病人体内易出现各种修饰变化,如氧化、脱酰胺化、糖基化等,这些修饰不仅会增加mAbs的异质性,还会影响其稳定性和生物活性,因此监测mAbs体内外修饰变化情况,对于药物研发、生产及体内命运动态变化分析意义重大。液质联用技术(LC-MS)通过将液相色谱分离和质谱检测相结合已成为抗体质量研究和临床监测的重要分析手段,而mAbs体内分析的生物样本前处理面临着基质干扰严重以及血药浓度低等分析挑战。系统总结了抗体修饰变异体分析技术涉及的样本前处理过程和LC-MS技术的应用进展。Therapeutic monoclonal antibodies(mAbs)are widely used in the efficient treatment of malignant tumors and autoimmune diseases due to their advantages of high targeting and potent effects,and have become a hotspot for new drug research and development worldwide.Due to the complex structure of antibody drugs,modification variants,such as oxidation,deamidation,glycosylation,etc.,easily occur in the process of production,storage,and even in patients,which not only increase the heterogeneity of the mAb,but also affect its stability and bioactivity,so the monitoring of the changes of mAb′s in vitro and ex vivo modification is essential for the analysis of the drug research and development,production,and the dynamics of the fate of mAb in vivo analysis.Liquid chromatography-mass spectrometry(LC-MS)has become an important analytical tool for antibody quality research and clinical monitoring by combining liquid chromatography separation and mass spectrometry detection,whereas the pre-treatment of biological samples for in vivo analysis of mAb faces analytical challenges such as severe matrix interferences as well as low blood drug concentrations.The sample pre-treatment process and the progress of the application of LC-MS technology involved in the analysis of antibody modification variants were summarised.

关 键 词：单克隆抗体 修饰变异体分析 样品前处理 基于质谱的蛋白质组学策略 液质联用技术 

分 类 号：R917[医药卫生—药物分析学]