Antibody-drug conjugates (ADCs) are powerful but analytically demanding therapeutic modalities. Each molecule carries multiple components—an antibody backbone, cytotoxic payload, linker, and sometimes targeting modifications—resulting in a highly heterogeneous mixture that evolves in vivo. This presentation offers a technically focused overview of how LC–MS is leveraged to quantify ADC-related analytes across development.
We’ll walk through representative strategies for quantifying free payload, conjugated (bound) payload, and total antibody, and briefly touch on emerging approaches in ADA monitoring via LC–MS. While this isn’t a deep-dive into method validation, it’s designed to help technical scientists and program leads make better decisions about assay selection, fit-for-purpose approaches, and the practical trade-offs involved in working with complex bioconjugates.