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

Xiaoyu Zhu; Shihan Huo; Chao Xue; Bo An; Jun Qu

doi:10.1016/j.jpha.2020.05.008

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

J Pharm Anal. 2020 Jun;10(3):209-220. doi: 10.1016/j.jpha.2020.05.008. Epub 2020 May 23.

Authors

Xiaoyu Zhu^{1

2}, Shihan Huo^{1

2}, Chao Xue^{2

3}, Bo An⁴, Jun Qu^{1

2}

Affiliations

¹ Department of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14214, USA.
² New York State Center of Excellence in Bioinformatics & Life Sciences, Buffalo, NY, 14203, USA.
³ Department of Chemical and Biological Engineering, School of Engineering and Applied Science, University at Buffalo, State University of New York, Buffalo, NY, 14260, USA.
⁴ Exploratory Biomarker, In-vitro/In-vivo Translation, R&D Research, GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Rd, Collegeville, PA, 19426, USA.

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); Drug-to-antibody ratio (DAR); Liquid chromatography-mass spectrometry (LCMS).

Publication types

Review