In Vitro/Vivo Characterization of ADC Drugs by Immunocapture and High-resolution Mass Spectrometry

Antibody drug conjugates (ADC) have made tremendous progress in the last ten years and have been one of the fastest growing anticancer drug modalities. However, the complex nature of ADC requires sophisticated bioanalysis strategies.

Generally, bioanalysis of the main component of ADCs (total antibody and intact ADC) has relied on ligand binding assays (LBAs) such as enzyme linked immunosorbent assay (ELISA). However, the inherent information of ADCs (such as drug to antibody ratio or possible biotransformations ) is mainly lost during the analysis by LBA. By comparison, intact LC MS assays have enabled quantitative and qualitative analysis of intact ADCs and circulating mass variants from in life studies, thus providing a better understanding of biologics to facilitate early drug discovery.

In this study, the intact LC MS method was used to study the in vitro/in vivo stability of trastuzumab emtansine (T-DM1). In addition, the quantitation of different DAR species of T DM1 was also discussed.