高宇雄, 钟大放. 抗体药物LC-MS法生物分析进展J. 药学学报, 2020,55(3): 453-462. doi: 10.16438/j.0513-4870.2019-0871
引用本文: 高宇雄, 钟大放. 抗体药物LC-MS法生物分析进展J. 药学学报, 2020,55(3): 453-462. doi: 10.16438/j.0513-4870.2019-0871
GAO Yu-xiong, ZHONG Da-fang. Advances in bioanalysis of antibody drugs by LC-MSJ. Acta Pharmaceutica Sinica, 2020,55(3): 453-462. doi: 10.16438/j.0513-4870.2019-0871
Citation: GAO Yu-xiong, ZHONG Da-fang. Advances in bioanalysis of antibody drugs by LC-MSJ. Acta Pharmaceutica Sinica, 2020,55(3): 453-462. doi: 10.16438/j.0513-4870.2019-0871

抗体药物LC-MS法生物分析进展

Advances in bioanalysis of antibody drugs by LC-MS

  • 摘要: 在抗体药物的生物分析中,液相色谱-质谱联用(LC-MS)技术已经成为传统配体结合分析(LBA)的一种重要的替代或补充方法。其方法开发中替代肽的选择、样品制备、灵敏度和定量准确性是值得关注的问题。本文对抗体药物LC-MS法生物分析的进展进行综述,介绍LC-MS法分析抗体药物的原理,说明LC-MS法定量抗体过程中面临的挑战与当前可用于应对这些挑战的新策略,包括:替代肽的选择、样品纯化与富集、提高酶解效率、肽段富集与应用低速LC等方面。本文最后展示了LC-MS技术在抗体药物生物分析中的应用实例,并对抗体药物LC-MS法的发展提出了展望。

     

    Abstract: Liquid chromatography-tandem mass spectrometry (LC-MS) is a promising alternative or complementary method for traditional ligand-binding assays (LBA) in antibody drug bioanalysis. However, issues related to method development, sample preparation, sensitivity and quantitative accuracy need to be addressed. This paper reviews progress in bioanalysis of antibody drugs by LC-MS methods, introduces the principle of the LC-MS method for the analysis of antibody drugs, and describes the challenges faced in quantitative antibody analysis by the LC-MS method. New strategies that can be used to deal with these challenges include:selection of surrogate peptides, purification and enrichment of samples, improvement in enzymatic digest efficiency, enrichment of peptides, and use of low rate LC. We review the application of LC-MS technology in the biological analysis of antibody drugs and discuss the prospect of using the LC-MS method for the analysis of antibody drugs.

     

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