Comparing ELSD and CAD Performance on Polysorbate Quantification in Infliximab Drug Products

Significance of the Topic

The nonchromophoric nature of polysorbates challenges conventional UV detection methods in biopharmaceutical analysis and drives the need for robust, high-throughput quantification techniques to ensure product safety and efficacy over shelf life.

Objectives and Study Overview

This study aimed to develop and optimize an intact polysorbate 80 assay for infliximab drug products using evaporative light scattering detection (ELSD) and charged aerosol detection (CAD) under Empower 3 control, with a focus on improving sensitivity through baseline subtraction and direct comparison of detector performance.

Methodology and Instrumentation

The analysis employed a trap-and-elute UPLC approach with an Oasis Max column on a Waters ACQUITY UPLC H-Class PLUS Bio System. PS80 standards and infliximab formulations were prepared in aqueous solutions. ELSD settings included 80 °C drift tube temperature and baseline subtraction processing in Empower 3. CAD was configured with low evaporation temperature and a power function of 1.2. Both detectors operated at a 2 Hz data rate.

Main Results and Discussion

Baseline subtraction in ELSD extended the linear dynamic range down to 0.01 mg/mL PS80 with an R2 of 0.993 and RSD below 2.5% in infliximab samples. CAD exhibited comparable limits of detection but required manual data curation due to baseline noise, yielding higher RSD (4–11%). Both detectors achieved an effective quantitation range of 0.01–1.0 mg/mL, but ELSD offered greater automation and processing consistency within Empower 3.

Advantages and Practical Applications of the Method

• Intact polysorbate analysis without hydrolysis or MS simplifies workflow and reduces instrument demands.
• Integrated ELSD under Empower 3 allows seamless baseline subtraction and automated peak processing.
• High sensitivity and throughput support routine quality control in biopharmaceutical manufacturing.
• Comparable performance to CAD with enhanced data processing capabilities.

Future Trends and Potential Applications

• Advancements in aerosol-based detector sensitivity and signal processing algorithms.
• Implementation of real-time PAT (process analytical technology) monitoring for excipient stability.
• Expansion to other nonchromophoric excipients and formulation components.
• Integration of detector data with AI-driven analytics for predictive quality control.

Conclusion

The optimized ELSD method with baseline subtraction delivers reliable, automated quantification of intact polysorbate in infliximab and biosimilar drug products with a 0.01–1.0 mg/mL dynamic range. Compared to CAD, ELSD under Empower 3 offers superior integration, consistency, and ease of use for biopharmaceutical quality control.

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