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.