An Introduction to Bioanalysis of Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are a rapidly evolving class of biotherapeutics mostly developed for the treatment of cancer. The ADC molecule typically comprises of a cytotoxic small-molecule drug covalently bound to a monoclonal antibody via a linker. Because of their complex structure combining large- and small-molecule drug characteristics and their heterogeneous and dynamic nature, unique bioanalytical strategies are needed to identify, characterize, and quantify ADCs for their safety and efficacy assessments. ADC bioanalysis thus necessitates an integrated bioanalytical approach including both ligand-binding assays and liquid chromatography coupled with mass spectrometry-based assays, conventionally used for large- and small-molecule bioanalysis, respectively. This chapter provides an introductory understanding of the structure and chemistry of ADC molecules and various bioanalytical strategies used for their pharmacokinetic and immunogenicity assessment.