QC friendly polysorbate quantification in high concentration protein samples

Polysorbate is a surfactant that serves an important role in stabilizing and solubilizing biologic drug products to prevent aggregation and generation of subvisible particles. Monitoring this low concentration excipient in complex formulations with high protein concentrations is required to ensure that the quality of the product is maintained, but interference from the protein poses a complex analytical problem. Many methods to monitor polysorbate content have been developed, but isolating this low concentration heterogeneous excipient from high protein concentration matrices continues to pose a problem in the pharmaceutical space. Here, we show a method for monitoring polysorbate concentration in high protein concentration-containing samples (e.g., > 100 mg/mL) using an HPLC-CAD. We confirm the method works for both PS-20 and PS-80 formulated biologics (mAbs, bioconjugates, antibody drug conjugates (ADCs)) and show the method tracks degradation of polysorbate in a formulated sample containing a high concentration monoclonal antibody. Finally, we show this method can be validated and transferred to other sites for testing and monitoring polysorbate concentration.