Following The PS80: How A Systematic LC-MS Investigation Turned A Potency Discrepancy Into A Path Forward

By Neil Lloyd, Scientist II / Group Lead, KBI Biopharma

Unexpected potency differences in monoclonal antibody programs can signal subtle molecular changes that are not easily detected with standard analytical assays. This article describes how a focused liquid chromatography–mass spectrometry (LC–MS) investigation can be used to uncover the root cause of such discrepancies.

By combining optimized chromatographic separations with detailed mass analysis, LC–MS enables characterization of low‑level structural or chemical modifications that directly impact biological activity. The approach allows teams to correlate specific product variants with changes in measured potency, providing clarity on whether the issue originates from degradation, processing conditions, or molecular instability.

This type of investigation supports faster resolution of discrepancies, reduces uncertainty during development, and informs corrective actions in both process and formulation design. Ultimately, it helps ensure consistent potency, regulatory confidence, and reliable performance of antibody therapeutics across development and manufacturing stages.