QC friendly polysorbate quantification in high concentration protein samples

Area of Science:

• Biopharmaceutical analysis
• Analytical chemistry
• Drug formulation

Background:

• Polysorbate (PS) is crucial for stabilizing biologic drugs, preventing aggregation and particle formation.
• Monitoring low PS concentrations in high-protein formulations (>100 mg/mL) is challenging due to protein interference.
• Existing analytical methods struggle to isolate PS from complex biologic matrices.

Purpose of the Study:

• To develop and validate a robust method for quantifying polysorbate in high-protein concentration biologic drug products.
• To demonstrate the method's applicability to various biologics, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs).
• To show the method can track polysorbate degradation in formulated samples.

Main Methods:

• High-Performance Liquid Chromatography coupled with Charged Aerosol Detection (HPLC-CAD) was employed.
• The method was optimized for analyzing samples with protein concentrations exceeding 100 mg/mL.
• Validation and transferability of the method were assessed.

Main Results:

• The HPLC-CAD method successfully quantified polysorbate (PS-20 and PS-80) in complex biologic formulations.
• The method demonstrated sensitivity in tracking polysorbate degradation in a high-concentration monoclonal antibody sample.
• The analytical method proved to be robust and suitable for routine monitoring.

Conclusions:

• HPLC-CAD offers a reliable solution for monitoring polysorbate content in challenging high-protein biologic formulations.
• This validated method supports quality control and stability assessment of biopharmaceutical products.
• The method's transferability facilitates its adoption across different pharmaceutical testing facilities.