The Ghost In The Gel: Tracking Down An Unexpected mAb Variant With LC-MS

By Ben Zigterman, Senior Scientist, KBI Biopharma

Monoclonal antibodies can develop low‑level variants during expression and manufacturing that may affect product quality, efficacy, or regulatory acceptance if left unidentified. The article outlines how a customized liquid chromatography–mass spectrometry (LC–MS) strategy can be used to detect and track these variants with high sensitivity and specificity.

By designing an analytical workflow tailored to the molecule and its known or suspected risks, developers can pinpoint subtle sequence or structural changes that are often missed by more conventional assays. The strategy combines optimized separation methods with mass analysis to distinguish true variants from background noise, enabling confident identification and ongoing monitoring throughout development.

This targeted LC–MS approach provides actionable insight into variant origin, prevalence, and process impact, helping teams make informed decisions earlier. Ultimately, it strengthens analytical control strategies, reduces downstream risk, and supports consistent manufacturing of high‑quality antibody therapeutics.