ADCs – LBA vs Hybrid: Hybrid LC-MS/MS Technology vs LBA for the Bioanalysis of Antibody-Drug-Conjugates Examples and Case Studies for Hybrid

In the last several years, we have seen the role of hybrid LC-MS/MS in the analysis of antibody-drug conjugates (ADC) increase due to the complexity and number of bioanalytical assays needed to support this modality in the drug development process. Typical antibody drug conjugates tend to consist of a toxic small molecule payload attached via a linker to an antibody. The approach or strategy needed to develop the various bioanalytical methods will be influenced by the type of conjugation and linker chemistry as well as the reagents available. Recently, we have seen a much wider application or use of “ADCs” to other modalities such as antibody-RNA conjugates, antibody-peptide conjugates or even other more complicated multi-functional entities. In many cases, ligand binding or hybrid LC-MS/MS may be applicable. However, poor reagents or limited availability of reagents can limit the immediate application of ligand-binding. The ability to approach the analysis from different angles to gain multiple insights into the analyte can increasingly nudge the decision towards the use of LC-MS/MS. This presentation will give an overview of ADC bioanalysis as well as several case studies to illustrate the various strategic approaches.