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Qualitative and quantitative characterization of protein biotherapeutics with liquid chromatography mass spectrometry
Mass Spectrometry Reviews ( IF 6.9 ) Pub Date : 2016-04-20 , DOI: 10.1002/mas.21500
Miao Qu 1, 2, 3 , Bo An 2, 3 , Shichen Shen 2, 3 , Ming Zhang 2, 3 , Xiaomeng Shen 2, 3 , Xiaotao Duan 4 , Joseph P. Balthasar 2 , Jun Qu 2, 3
Affiliation  

In the last decade, the advancement of liquid chromatography mass spectrometry (LC/MS) techniques has enabled their broad application in protein characterization, both quantitatively and qualitatively. Owing to certain important merits of LC/MS techniques (e.g., high selectivity, flexibility, and rapid method development), LC/MS assays are often deemed as preferable alternatives to conventional methods (e.g., ligand‐binding assays) for the analysis of protein biotherapeutics. At the discovery and development stages, LC/MS is generally employed for two purposes absolute quantification of protein biotherapeutics in biological samples and qualitative characterization of proteins. For absolute quantification of a target protein in bio‐matrices, recent work has led to improvements in the efficiency of LC/MS method development, sample treatment, enrichment and digestion, and high‐performance low‐flow‐LC separation. These advances have enhanced analytical sensitivity, specificity, and robustness. As to qualitative analysis, a range of techniques have been developed to characterize intramolecular disulfide bonds, glycosylation, charge variants, primary sequence heterogeneity, and the drug‐to‐antibody ratio of antibody drug conjugate (ADC), which has enabled a refined ability to assess product quality. In this review, we will focus on the discussion of technical challenges and strategies of LC/MS‐based quantification and characterization of biotherapeutics, with the emphasis on the analysis of antibody‐based biotherapeutics such as monoclonal antibodies (mAbs) and ADCs. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:734–754, 2017

中文翻译:

液相色谱质谱法对蛋白质生物治疗剂的定性和定量表征

在过去的十年中,液相色谱质谱(LC / MS)技术的发展已使其在定量和定性蛋白质表征中得到广泛应用。由于LC / MS技术的某些重要优点(例如,高选择性,灵活性和快速的方法开发),LC / MS分析通常被认为是常规方法(例如配体结合分析)替代方法,用于蛋白质分析生物治疗学。在发现和开发阶段,LC / MS通常用于生物样品中蛋白质生物治疗药物的绝对定量和蛋白质定性表征的两个目的。为了对生物基质中的目标蛋白质进行绝对定量,最近的工作已导致LC / MS方法开发,样品处理,富集和消化,以及高性能低流量LC分离。这些进步提高了分析灵敏度,特异性和鲁棒性。关于定性分析,已开发出一系列技术来表征分子内二硫键,糖基化,电荷变异,一级序列异质性以及抗体药物偶联物(ADC)的药物与抗体的比率,这使我们能够精化评估产品质量。在本综述中,我们将重点讨论基于LC / MS的生物治疗药物定量和表征的技术挑战和策略,重点是基于抗体的生物治疗药物(如单克隆抗体(mAb)和ADC)的分析。©2016 Wiley Periodicals,Inc.质谱Rev 36:734–754,2017 这些进步提高了分析灵敏度,特异性和鲁棒性。关于定性分析,已开发出多种技术来表征分子内二硫键,糖基化,电荷变体,一级序列异质性以及抗体药物偶联物(ADC)的药物与抗体的比率,这使我们能够精化评估产品质量。在本综述中,我们将重点讨论基于LC / MS的生物治疗药物定量和表征的技术挑战和策略,重点是基于抗体的生物治疗药物(如单克隆抗体(mAb)和ADC)的分析。©2016 Wiley Periodicals,Inc.质谱Rev 36:734–754,2017 这些进步提高了分析灵敏度,特异性和鲁棒性。关于定性分析,已开发出多种技术来表征分子内二硫键,糖基化,电荷变体,一级序列异质性以及抗体药物偶联物(ADC)的药物与抗体的比率,这使我们能够精化评估产品质量。在本综述中,我们将重点讨论基于LC / MS的生物治疗药物定量和表征的技术挑战和策略,重点是基于抗体的生物治疗药物(如单克隆抗体(mAb)和ADC)的分析。©2016 Wiley Periodicals,Inc.质谱Rev 36:734–754,2017 已经开发了一系列技术来表征分子内二硫键,糖基化,电荷变异,一级序列异质性以及抗体药物偶联物(ADC)的药物与抗体的比率,这使评估产品质量的能力得以提高。在本综述中,我们将重点讨论基于LC / MS的生物治疗药物定量和表征的技术挑战和策略,重点是基于抗体的生物治疗药物(如单克隆抗体(mAb)和ADC)的分析。©2016 Wiley Periodicals,Inc.质谱Rev 36:734–754,2017 已经开发了一系列技术来表征分子内二硫键,糖基化,电荷变异,一级序列异质性以及抗体药物偶联物(ADC)的药物与抗体的比率,这使评估产品质量的能力得以提高。在本综述中,我们将重点讨论基于LC / MS的生物治疗药物定量和表征的技术挑战和策略,重点是基于抗体的生物治疗药物(如单克隆抗体(mAb)和ADC)的分析。©2016 Wiley Periodicals,Inc.质谱Rev 36:734–754,2017 从而提高了评估产品质量的能力。在本综述中,我们将重点讨论基于LC / MS的生物治疗药物定量和表征的技术挑战和策略,重点是基于抗体的生物治疗药物(如单克隆抗体(mAb)和ADC)的分析。©2016 Wiley Periodicals,Inc.质谱Rev 36:734–754,2017 从而提高了评估产品质量的能力。在本综述中,我们将重点讨论基于LC / MS的生物治疗药物定量和表征的技术挑战和策略,重点是基于抗体的生物治疗药物(如单克隆抗体(mAb)和ADC)的分析。©2016 Wiley Periodicals,Inc.质谱Rev 36:734–754,2017
更新日期:2016-04-20
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