Quantitation of MMAE and the Antibody of the Antibody Drug Conjugate Anetumab-MMAE From Rat Plasma Using HPLC-MS/MS and HPLC-HRMS/MS
Authors: Chad David Christianson; Jason Scott Watts; Jennifer S Zimmer; Balaganesh Kuruba
Presented by Chad Christianson at the ASMS 73rd Conference on Mass Spectrometry and Allied Topics
Anetumab-MMAE is an antibody drug conjugate (ADC) composed of a human anti-mesothelin antibody linked to the anti-mitotic cytotoxic agent monomethyl auristatin (MMAE). The ADC targets cancer cells by immune recognition with a receptor-mediated endocytosis cellular MMAE delivery mechanism. Inside the cell, the MMAE binds to tubulins and interrupts the microtubule dynamics resulting in cellular death. Quantitation of ADCs typically require three different measurements using multiple extraction methods and sample aliquots. Free MMAE, conjugated MMAE and total antibody concentrations must be measured and reported. A simple method has been developed in order to quantify all three components. The free and conjugated MMAE was measured using HPLC-MS/MS and the total antibody was quantified using HPLC-HRMS/MS.
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