High-Resolution Characterization of ADCs by Orbitrap LCMS.

Antibody-drug conjugates (ADCs) have complex molecular structures as they are composed of both small and large molecules, and they often undergo biotransformation over time in circulation. Here we describe a high-resolution Orbitrap MS approach for the characterization of ADC biotransformation and stability. Compared with conventional approach by Q-TOF MS, the method described here significantly improved the mass resolution and enabled more comprehensive characterization of ADC catabolites. It is particularly beneficial for characterizing ADC biotransformations with small mass changes.