LC-MS/MS技术在蛋白质药物定量分析中的应用

近年来,蛋白质药物已经成为全球制药业的研发热点。建立灵敏、准确、高通量的蛋白质药物定量分析方法,是进行蛋白质药物研究的关键前提,也是蛋白质药物研究的难点。随着液相色谱串联质谱技术（LC-MS/MS）的发展,其在蛋白质药物定量分析中起着越来越重要的作用。本文首先综述了蛋白质药物的分类,然后比较了LC-MS/MS技术与传统配体结合测定方法（LBA）在蛋白质药物分析中的优缺点,以及分析了LC-MS/MS技术在蛋白质药物定量分析中的常见问题、解决方法、应用方向等。最后预测,短时间内LC-MS/MS 不会完全取代传统的LBA方法,随着LC-MS/MS技术和生物化学技术的充分结合,蛋白质药物分析将会得到飞速的发展。

Quantitative characterization of protein protein drugs by liquid chromatography coupled with mass spectrometry

The development of protein drugs for disease treatments has thrived in the last decades, which have garnered substantial interest from the biopharmaceutical industry. Qualitative characterization with high accuracy, sensitivity, and selectivity is essential to support development of protein drugs. With the development of liquid chromatography tandem mass spectrometry (LC-MS/MS) techniques, it has been playing an increasingly important role in the analysis of protein drugs. In this review, we will focus on the discussion of the advantage and disadvantage of LC-MS/MS compared with Ligand-binding assays (LBA) in the analysis of protein drugs, the challenges of LC-MS/MS techniques in protein drugs analysis and summarizes recently developed methods to overcome these challenges. In addition, the applications of LC-MS/MS techniques on quantification and characterization of Antibody drug conjugates (ADCs) are also discussed. We deduce that despite the obvious advantage of LC-MS/MS, it will not fully replace LBA assays in the near future. The conjunction of biochemical techniques with LC/MS will provide a thrust for rapid development of protein drug.