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Poster

A Sensitive LC-MS/MS Method for the Determination of DM4 and DM4-Me in Human Plasma

June 15, 2020

WRIB 2020 -- Antibody-drug conjugates (ADCs) are a novel class of therapeutic agents, in which one or more small cytotoxic molecules (payload) are linked covalently to a monoclonal antibody (mAb). The exposure of unconjugated payload and/or its metabolites in circulation is important for the evaluation of the safety and efficacy of ADCs. In this work, we describe the development and validation of an LC-MS/MS method for the determination of unconjugated DM4 and its metabolite DM4-Me in human plasma. DM4, a derivative of maytansine, is the cytotoxic payload of an ADC developed at Novartis. DM4 contains a free sulfhydryl group, which reacts with other thiol-containing molecules in biological matrices to form conjugates, leading to underestimation of the free payload concentration. This renders a technical challenge in developing a robust bioanalytical assay in support of clinical development