LOCALIZING THE CONJUGATION SITES OF CYSTEINE-CONJUGATED ANTIBODY DRUG CONJUGATES BY IMPROVED LC-MS SUBUNIT ANALYSIS FOR ADC POSITIONAL ISOMER IDENTIFICATION

摘要

Limited Lys-C digestion protocol developed is more effective in the cleavage of the ADC hinge region moiety than the SpeB approach. Oxidation and loss of water were observed for the Fc and LC+Drug fragments. Positional isomers of Cysteine-conjugated ADCs can be confirmed by targeted MS/MS experiments by middle-down approach.