摘要
单克隆抗体(简称单抗)药物的研究和开发是一个快速发展的领域,从第一代鼠源到第四代全人源单抗,单抗药物在多种疾病治疗中的疗效和安全性不断提高,目前我国也进入单抗药物研发的快车道。为规范单抗药物研发与评价,欧美各国药品监管机构和药典现已开始发布单抗及其生物类似药质量评价试验要求与接受标准。在评价单抗相关产品质量特性或制定质量评价标准时,质谱技术因具有高灵敏度、分辨率、选择性和特异性,已经成为单抗质量分析的重要工具。基于质谱技术的单抗药物研究涉及结构表征、杂质分析、药代动力学/药效学研究等。本文综述了现行的单抗药物质量控制要求以及质谱技术在单抗药物质量分析中研究和应用,为全面表征单抗质量属性的研究提供参考和借鉴。
The research and development of monoclonal antibodies(mAbs)is a rapidly developing field.From the first generation of murine mAbs to the fourth generation of fully human mAbs,the efficacy and safety of mAbs in the treatment of various diseases have been continuously improved.In order to regulate the development and evaluation of mAbs,drug regulatory agencies and pharmacopeias of America and China have tried to issue feasible test procedures and acceptance criteria for quality evaluation of mAbs and biosimilars.Mass spectrometry(MS)technique with high sensitivity,resolution,selectivity,and specificity has become an important tool to evaluate the quality characteristics of monoclonal antibody-related products or specify mAb quality.The research of MS-based monoclonal antibody study involves structure characterization,impurity analysis,pharmacokinetics/pharmacodynamics(PK/PD),etc.This review focuses on the current quality control requirements of mAb related products and the development of MS technique for mAb quality characterization and specification.It is expected to provide information and references for evaluating the quality of monoclonal antibodies under research and development.
作者
朱文文
李梦林
张金兰
ZHU Wen-wen;LI Meng-lin;ZHANG Jin-lan(State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)
出处
《药学学报》
CAS
CSCD
北大核心
2020年第12期2843-2853,共11页
Acta Pharmaceutica Sinica
基金
中国医学科学院医学与健康科技创新工程(药物药效和安全性相关的关键分析新技术研究,2016-I2M-3-010)
国家重点研发计划(高灵敏度糖蛋白鉴定方法研发及其在药物杂质分析中的应用,2018YFF0212504).
关键词
单克隆抗体
质量评价标准
质谱技术
结构表征
杂质分析
药代动力学/药效学研究
therapeutic monoclonal antibody
quality standard
mass spectrometry
structure characterization
impurity analysis
pharmacokinetics/pharmacodynamics
