Characterization of Interchain Cysteine Linked Antibody Drug Conjugates in Mouse Plasma by LC/MS

Antibody-drug conjugates (ADCs) have become promising therapy for the treatment of cancers. Among all the ADCs under development, 2/3 of them are interchain cysteine-linked ADCs. The ADCs are manufactured by partially reducing the 4 pairs of interchain disulfide bonds followed by conjugate cytotoxic payloads to the thiols, as a consequence, the antibodies are linked with 0, 2, 4, 6, 8 drugs. The drug-to-antibody ratio (DAR) and the drug linking position are important parameters that affect the therapeutic effects and need to be well characterized. In this study, we successfully characterize a method for the interchain cysteine linked ADC in a biological matrix.