Antibody-drug conjugates (ADCs) are among the most promising—and analytically demanding—modalities in biopharma today. By combining large, heterogeneous antibodies with chemically labile payloads and linkers, ADCs introduce a level of structural complexity that challenges conventional analytical workflows. It also poses the challenge that the very features you need to measure are often the easiest to lose during analysis.
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Why traditional MS/MS falls short for ADCs and how electron-activated dissociation (EAD) changes the equation
Antibody-drug conjugates (ADCs) are among the most promising—and analytically demanding—modalities in biopharma today. By combining large, heterogeneous antibodies with chemically labile payloads and linkers, ADCs introduce a level of structural complexity that challenges conventional analytical workflows. It also poses the challenge that the very features you need to measure are often the easiest to lose during analysis.
Managing ADC characterization: The challenge of turning complexity into confidence
Unlike traditional monoclonal antibodies, ADCs combine an antibody backbone with linker chemistry and a cytotoxic payload. This multi-component architecture introduces overlapping layers of heterogeneity, including drug-to-antibody ratio (DAR) distributions, charge variants, post-translational modifications, and structural changes at both the intact and subunit levels. Across ADC development, these characteristics are considered critical quality attributes that must be characterized, understood, and monitored.
ADC analytics FAQs: Answering the most common questions about ADC characterization
Antibody-drug conjugates (ADCs) have emerged as one of the fastest-growing classes of biotherapeutics, combining the targeting specificity of monoclonal antibodies with the potency of cytotoxic payloads. However, this unique architecture also introduces significant analytical complexity. From drug-to-antibody ratio (DAR) distributions and charge variants to conjugation sites and structural modifications, ADCs present multiple, interconnected sources of heterogeneity that must be understood to ensure product quality and performance.
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