Method Transfer and High-Speed Analysis of Impurities of Drug by Prominence-i

Significance of the Topic

Bepotastine besilate is a selective histamine H1 antagonist used to treat ocular itching in allergic conjunctivitis. With its recent inclusion in the Japanese Pharmacopoeia Sixteenth Edition Supplement II, rigorous impurity profiling is essential to ensure safety and compliance in pharmaceutical quality control.

Aims and Study Overview

This work evaluates method transfer and performance of the new Prominence-i integrated HPLC system relative to a conventional Shimadzu LC-2010 and a third-party instrument. Compliance with the Japanese Pharmacopoeia monograph for bepotastine besilate related substances was assessed, and a high-speed analysis protocol using a low-volume tubing kit was developed.

Materials and Methods

Analytical conditions for standard and high-speed methods:

• Standard Method: Shim-pack VP-C8 column (150 × 4.6 mm, 5 μm), flow 1.0 mL/min, mobile phase A: 50 mM phosphate buffer pH 3.0; B: acetonitrile with 5.7 mM pentanesulfonate (30 % B); column 40 °C; inj 20 μL; detection 220 nm; conventional flow cell.
• High-Speed Method: Shim-pack XR-C8 column (75 × 3.0 mm, 2.2 μm), flow 1.0 mL/min, same mobile phases, inj 1 μL; high-speed high-sensitivity flow cell; low-volume tubing kit installed.

Instrumention Used

• Shimadzu Prominence-i integrated HPLC
• Shimadzu LC-2010 integrated HPLC
• Third-party HPLC system
• LC-2030C 3D diode array detector

Main Results and Discussion

Chromatograms from the three systems demonstrate equivalent separation of bepotastine and related impurities under pharmacopoeial conditions. System suitability criteria—peak area response, theoretical plates > 3000, symmetry factor 0.8–1.5, and peak area RSD < 2 %—were met across all configurations. The delay-volume compatible kit on Prominence-i reproduced LC-2010 performance precisely. High-speed analysis reduced the main peak retention to ~1.2 min, cutting run time and solvent use by fourfold while delivering an ~8.5× sensitivity improvement; suitability metrics remained compliant.

Practical Benefits and Applications

The validated method transfer strategy enables laboratories to adopt Prominence-i without requalification delays. High-speed protocols boost throughput and reduce solvent consumption, supporting cost-effective and sustainable impurity profiling in routine QA/QC environments.

Future Trends and Potential Uses

• Further miniaturization of flow paths and columns for ultrafast analysis
• Integration with mass spectrometry for enhanced impurity identification
• Automation and AI-driven method optimization for adaptive quality control
• Adoption of low-solvent and green chromatography approaches

Conclusion

The Prominence-i system, with optional delay-volume and low-volume tubing kits, meets Japanese Pharmacopoeia standards and supports seamless method transfer and high-speed impurity analysis of bepotastine besilate, delivering robust, high-throughput performance for pharmaceutical laboratories.

Reference

• Japanese Pharmacopoeia Sixteenth Edition, Supplement II – Official Monographs (Chemicals, etc.) – Bepotastine Besilate