Transition of average drug-to-antibody ratio of trastuzumab deruxtecan in systemic circulation in monkeys using a hybrid affinity capture liquid chromatography-tandem mass spectrometry

Abstract

Trastuzumab deruxtecan (T-DXd, DS-8201a) is an antibody–drug conjugate, comprising an anti-HER2 antibody at a drug-to-antibody ratio of 7–8 with the topoisomerase I inhibitor DXd. In this study, the concentrations of antibody-conjugated DXd and total antibody were determined and observed to decrease over time following intravenous administration of T-DXd to monkeys. The drug-to-antibody ratio of T-DXd also decreased in a time-dependent manner, which reached approximately 2.5 in 21 days after administration. It was suggested that antibody-conjugated DXd of T-DXd was relatively stable in vivo compared with that of other reported antibody–drug conjugates.