USP Method Transfer of Donepezil Tablets from HPLC to UPLC

Importance of the topic

Reliable and efficient pharmaceutical analysis is essential for quality control, regulatory compliance and cost containment. Transferring compendial USP methods from high-performance liquid chromatography (HPLC) to ultra-performance liquid chromatography (UPLC) can dramatically increase sample throughput, reduce solvent consumption and improve method robustness when analyzing formulated drug products with complex excipients.

Objectives and study overview

This study aimed to adapt the USP monograph assay and organic-impurity methods for donepezil tablets from an HPLC platform to UPLC. Key goals included:

• Scaling chromatographic conditions to UPLC columns
• Assessing system suitability against USP criteria
• Evaluating long-term robustness in routine QC-style injections

Methodology

The USP HPLC method used an XBridge C18 4.6 × 250 mm, 5 µm column with a 50-minute gradient. Sample preparation required dissolution, 0.2 µm filtration and centrifugation to remove particulates. The method was scaled to UPLC using the ACQUITY Columns Calculator, targeting a BEH C18 2.1 × 100 mm, 1.7 µm column. Gradient times and flow rates were adjusted for consistent selectivity at higher linear velocity. Two routine-use evaluations were performed:

1. UPLC BEH C18 1.7 µm column with repeated tablet injections until system suitability failed
2. XP C18 2.1 × 100 mm, 2.5 µm column to compare durability under similar conditions

Used instrumentation

• HPLC: Alliance 2695 with XBridge C18 5 µm column
• UPLC: ACQUITY UPLC H-Class with BEH C18 1.7 µm and XBridge C18 XP 2.5 µm columns
• Detection: UV at 286 nm
• Data system: Empower 3 CDS

Main results and discussion

The UPLC method reduced run time from 50 min to 12.5 min (75% time saving) and cut solvent and sample usage by 92%. System suitability criteria (retention time, %RSD, tailing and plate count) met USP limits. In routine use, the BEH C18 column maintained suitability for ~850 injections before plate count decline and peak splitting occurred, attributed to excipient build-up. Switching to the XP 2.5 µm column doubled column life to ~1 600 injections while still achieving 80% faster analysis than HPLC and the same solvent savings.

Benefits and practical applications

• Significant throughput increase for QC laboratories
• Major reduction in solvent costs and waste
• Improved robustness when analyzing complex tablet matrices
• Regulatory compliance with USP monograph requirements

Future trends and potential applications

Advances in column chemistries and particle technologies will further enhance method durability and speed. Integration with automated sample preparation, real-time monitoring and greener mobile-phase alternatives are anticipated. UPLC method transfers will expand to more monographs, supporting high-throughput pharmaceutical screening and process analytical technology (PAT).

Conclusion

The USP donepezil tablet assay and impurity methods were successfully transferred from HPLC to UPLC. Using BEH C18 1.7 µm and XP C18 2.5 µm columns delivered 80–75% faster runs and 92% solvent/sample savings. The XP chemistry provided enhanced ruggedness under heavy routine use, demonstrating a practical approach to modernizing compendial methods for improved laboratory efficiency.

References

1. Jones M.D., Alden P., Fountain K.J., Aubin A. Implementation of Methods Translation between Liquid Chromatography Instrumentation, Waters Application Note 2010, Part No. 720003721EN.
2. USP Monograph. Donepezil Hydrochloride, USP35-NF30. United States Pharmacopeial Convention, effective May 1, 2012.