Apply hybrid (LBA)-LC-MS/MS approach to the determination of total sBCMA in the presence of an antibody drug

CBF 2.0 2025 -- B-cell maturation antigen (BCMA or BCM), is a protein that in humans is encoded by the TNFRSF17 gene. Membrane-bound BCMA can be cleaved by γ-secretase and shed as soluble BCMA (sBCMA). sBCMA can act as a neutralizing sink to compete with drug, as well as serve as a diagnostic/prognostic biomarker for multiple myeloma (MM). Shedding of transmembrane proteins and release into the circulation have been reported for several biotherapeutic targets. Quantification of dynamic levels of shed target receptors may be essential for understanding the impact on drug development. In this study, we presented a bioanalytical approach to select a fit-for-purpose assay for total shed BCMA levels in clinical studies.