首页|质谱技术在兽用治疗性蛋白药物表征和定量分析上的应用

质谱技术在兽用治疗性蛋白药物表征和定量分析上的应用

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治疗性蛋白药物已成为药物开发的一个重要分支,由于其具有良好的临床获益和安全性,现已成为肿瘤、自身免疫等疾病治疗的重点研发药物。通过体外细胞表达的治疗性蛋白药物通常具有高度复杂性,因此,在开发或生产过程中建立一系列质量分析和评价标准来保证药物的一致性和安全性尤为重要。质谱技术已被广泛用于小分子药物开发,具有灵敏度高、选择性和特异性良好、高通量等优点,该技术已逐步成为治疗性蛋白药物质量分析研究的重要工具,用于治疗性蛋白药物结构表征、翻译后修饰分析、定量分析、杂质分析及相互作用等研究。笔者综述了常用于蛋白质分析的质谱组成,包括常见电离方式、解离方式和质量分析仪;在此基础上,对利用质谱技术进行治疗性蛋白药物定性、翻译后修饰(糖基化、二硫键)研究的一般样品处理方法和质谱方法进行分析,并对利用质谱技术进行蛋白质定量分析方法开发、样品前处理和常用分析程序进行分析阐述;同时,笔者也对抗体药物偶联物(antibody-drug conjugate,ADC)表征、定量分析和其他质谱分析表征应用的一般方法进行总结。通过对上述内容研究分析,旨在为利用质谱技术加快兽用治疗性蛋白药物开发和研究提供参考和借鉴。
Application of Mass Spectrometry Techniques in the Characterization and Quantitative Analysis of Therapeutic Protein Drugs in Veterinarian
Therapeutic protein drugs have evolved into a crucial branch of drug research and development.Due to their remarkable clinical efficacy and safety profile,they have become the preferred choice for treating conditions like cancer and autoimmune disorders.Therapeutic protein drugs produced through in vitro cell expression are often highly complex.Therefore,it is essential to establish a series of quality analysis and standards to ensure consistency and safety during the development and production processes.Mass spectrometry technology,known for its high sensitivity,excellent selectivity,specificity and high throughput capabilities,has been widely employed in the development of small molecule drugs.It has also emerged as a vital tool for the quality analysis of therapeutic protein drugs,contributing to structural characterization,post-translational modification assessment,quantitative analysis,impurity analysis and interaction studies.This article offers a comprehensive overview of protein analysis through mass spectrometry,including ionization techniques,dissociation methods and mass analyzers.Moreover,it delves into the sample preparation and methodologies for protein structural characterization and post-translational modification analysis such as glycosylation and disulfide bonds.The article also explores techniques for protein quantification via mass spectrometry,covering sample pre-processing and standard analytical procedures.Moreover,it also provides an outline of general strategies for characterizing and quantifying antibody-drug conjugate(ADC)and application in other way.By comprehensively exploring these topics,this article aims to provide valuable insights and reference to advance veterinary therapeutic protein drug research and development through mass spectrometry technology.

therapeutic protein drugsmass spectrometry techniquesquality control and evaluationquantitative analysis

邱基程、杨宇欣、张璐、温泽宇、陈苏蒙、曹兴元

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中国农业大学动物医学院,北京 100193

中国农业大学国家兽药安全评价中心,北京 100193

治疗性蛋白药物 质谱分析技术 质量控制分析 定量分析

国家重点研发计划项目

2018YFD0500301

2024

中国畜牧兽医
中国农业科学院北京畜牧兽医研究所

中国畜牧兽医

CSTPCD北大核心
影响因子:0.72
ISSN:1671-7236
年,卷(期):2024.51(6)