Revealing mAb Oligomers that Skew Concentration in High mAb Formulations; Using CG-MALS and Native IM-MS to Improve Dose Accuracy

Monoclonal antibody formulations require high protein concentrations and tailored excipients for stability and safe delivery. Formulation choices (pH, buffer, ionic strength, excipients) govern colloidal interactions and reversible/irreversible self-association, where dimers and higher oligomers reduce effective monomer concentration, impacting dose accuracy and degradation pathways. Traditional UV/Vis cannot distinguish monomers from reversible oligomers, and aggregation assays may miss transient species. Composition Gradient Multi-Angle Light Scattering (CG-MALS) elucidates stoichiometry across concentration gradients, quantifying monomer fractions and equilibrium oligomers under formulation-relevant conditions. Native ion mobility mass spectrometry (IM-MS) preserves noncovalent assemblies to resolve stoichiometries and provide collision cross sections, confirming oligomer identities. Together, these orthogonal, native-condition tools yield actionable data to select excipients, set accurate oligomer limits, ensure manufacturability, and strengthen regulatory control. Download the poster to learn more.