Antibody-drug conjugates (ADCs) are promising targeted cancer therapies that combine the specificity of monoclonal antibodies specificity with potent cytotoxic payloads. Traditional ligand-binding assays (LBAs) have been widely utilized for ADC bioanalysis but are hindered by limitations such as low specificity and selectivity, complex critical reagents, lengthy method development, and the capability to measure only the antibody component. Liquid chromatography-mass spectrometry (LCMS) presents a promising alternative, offering precise and multiplexed bioanalysis that overcomes the shortcomings of LBAs. This study successfully developed the robust LCMS-based methods to quantify both payload and antibody for RBM-ADC-188 using the Shimadzu 30 series UPLC coupled with a Sciex 6500+ MS, addressing its complex structure and enabling accurate quantification essential for pre-clinical development. LCMS offers superior bioanalytical capability compared to traditional LBAs, providing precise and comprehensive measurements of total antibody, ADC, conjugated payload and free payload. This approach significantly streamlines the bioanalytical workflow for ADC drugs.
Learning Objectives:
Upon completion, participant will be able to understand the strategies for how to quantify payload and antibody in ADC only using LCMS.
Upon completion, participant will be able to understand the chanllenges during quantifying payload and antibody in ADC using LCMS.
Upon completion, participant will be able to understand the solutions for how to quantify payload and antibody IN ADC using LCMS.
