Highly Sensitive Charge Variant Analysis Of Complex Biopharmaceuticals

With the rise of precision medicine, the monoclonal antibody (mAb) market has expanded enormously during recent years. Monoclonal antibodies are large biomolecules that are produced by recombinant means and therefore can be highly heterogeneous. For therapeutic use, knowledge of this microheterogeneity is mandated by authorities to guarantee patient safety.

Charge variant analysis on the intact protein level represents an extremely powerful tool to distinguish protein isoforms based on differential surface charge, requiring minimal sample preparation and short analysis times. Recently, efforts were undertaken to combine charge variant separation of proteins with powerful detection modes such as mass spectrometry, creating new and exciting methods for protein characterisation.

This case study explores the use of a capillary electrophoresis device to perform highly selective charge variant separation of complex pharmaceuticals for native intact antibodies while generating excellent quality MS data. This technology allows for in-depth analysis of extremely low abundant charge variants with outstanding method sensitivity.