Characterizing Antibody-Drug Conjugates with Charge Detection Mass Spectrometry

Mass spectrometry (MS) has emerged as a powerful analytical tool for the investigation of antibody drug conjugates (ADCs), enabling the determination of drug-to-antibody ratio (DAR) and monitoring of ADC metabolism. High DAR ADCs have been developed to improve ADC potency, but conventional native MS is often insufficient to characterize these molecules due to their heterogeneity and low concentration in complex biomatrices.

Recently, native charge detection MS (CDMS) has been developed to study biotherapeutics by determining the charge and the m/z of ions simultaneously. In this study, the native CDMS is coupled with the SampleStream platform and Newomics’ MnESI source to investigate the DAR values and the stability profile of two interchain modified high DAR ADCs. We started our work by determining the DAR values of the ADCs from the stock solutions using native CDMS. We also applied native CDMS platform for ex vivo and in vivo ADC samples where the concentration of ADC was lower than that from the formulation buffer. The results indicate that our native CDMS platform can serve as automated and sensitive tool to characterize high DAR ADCs and their stability from complex biomatrices.

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