Current LC-MS-based strategies for characterization and quantification of antibody-drug conjugates

Abstract

The past few years have witnessed enormous progresses in the development of antibody-drug conjugates (ADCs). Consequently, comprehensive analysis of ADCs in biological systems is critical in supporting discovery, development and evaluation of these agents. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a promising and versatile tool for ADC analysis across a wide range of scenarios, owing to its multiplexing ability, rapid method development, as well as the capability of analyzing a variety of targets ranging from small-molecule payloads to the intact protein with a high, molecular resolution. However, despite this tremendous potential, challenges persist due to the high complexity in both the ADC molecules and the related biological systems. This review summarizes the up-to-date LC-MS-based strategies in ADC analysis and discusses the challenges and opportunities in this rapidly-evolving field.

Keywords

• Antibody-drug conjugate (ADC)
• Liquid chromatography-mass spectrometry (LCMS)
• Drug-to-antibody ratio (DAR)