The integration of ligand-binding assay and LC-MS/MS (immunocapture-LC-MS) has unleashed the combined advantages of both powerful techniques for addressing the ever increasing bioanalytical challenges for biotherapeutics and biomarker assays. The highly specific, selective and sensitive characteristics of the immunocapture-LC-MS-based assays have enabled the determination of biotherapeutics and biomarkers in biomatrices with ease of method development, less requirements on key reagents as well as structural specificity for endogenous and engineered biomolecules. In addition, the versatile immunocapture-LC-MS technology has expanded into many challenging areas to enhance mechanistic studies of drug interactions with their targets. This paper intends to summarize our perspectives on enhancing the use of immunocapture-LC-MS in drug discovery and development for emerging new modalities.
Keywords: ADAs; ADCs; LBA; antibody isotyping; antidrug antibodies; antidrug conjugates; aptamers; exosome; immunocapture-LC–MS; intact protein analysis; ligand-binding assays; target engagement; target turnover.