USP Method Transfer and U P LC Method for Analysis of Mometasone Furoate Ointment

Significance of the Topic

Mometasone furoate ointment is a widely used topical corticosteroid for inflammatory skin disorders such as dermatitis, psoriasis and eczema. Reliable and efficient quantitative assays are essential for quality control, regulatory compliance and formulation development. Transitioning from conventional HPLC to UPLC delivers substantial gains in speed, solvent consumption and chromatographic performance, directly impacting cost, throughput and environmental footprint

Objectives and Study Overview

This work aimed to transfer the official USP HPLC compendial assay for mometasone furoate 0.1% ointment onto an ACQUITY UPLC platform using sub-2 µm particle technology. Key goals included reducing run time, cutting mobile phase and sample use, and evaluating long-term robustness over more than 3000 injections in a routine QC setting

Methodology and Instrumentation

The original USP method employed Waters Alliance HPLC with a 4.6 × 250 mm, 5 µm XBridge Shield RP18 column, a 2.0 mL/min gradient (70–30% to 45–55% water:acetonitrile) at 25 °C, 254 nm detection and 20 µL injections. Sample and internal standard (diethyl phthalate) preparations followed USP diluents and concentration guidelines. The UPLC variant used ACQUITY UPLC with a 2.1 × 75 mm, 1.7 µm BEH Shield RP18 column, 0.55 mL/min flow, identical gradient proportions, 1.3 µL injection and PDA detection. Method transfer employed Waters UPLC Columns Calculator and Empower 2 CDS for data management

Main Results and Discussion

The UPLC method achieved a 78% shorter analysis time (from ~50 min to ~11 min) and a 94% reduction in mobile phase (6.2 mL vs. 100 mL) and sample consumption per injection. Chromatograms showed sharper peaks and equivalent retention times. System suitability tests met USP criteria with tailing factors ≤ 1.05 and RSD ≤ 0.2%. In a routine use study over 3000 injections, tailing factors remained stable (~1.05), RSD and retention time variability stayed within limits, and system pressure trends were consistent. Minor pressure increases at ~2500 injections were resolved by replacing the in-line filter, and temperature fluctuations had negligible impact on performance

Benefits and Practical Applications

• Significant cost savings in solvent, sample and waste disposal
• Higher sample throughput supporting faster QC release and reduced backlog
• Improved chromatography with narrower peaks enhances assay sensitivity and specificity
• Robust long-term operation suitable for high-volume pharmaceutical QC laboratories

Future Trends and Potential Applications

Advances in UPLC and sub-2 µm technology will drive greener analytical workflows with even lower solvent use. Integration with automated sample preparation and real-time data analysis using artificial intelligence promises further efficiency. Expanding method transfer tools will simplify cross-platform implementation across diverse pharmaceutical assays

Conclusion

The successful transfer of the USP mometasone furoate ointment assay to UPLC demonstrates dramatic improvements in speed, resource efficiency and robustness without compromising chromatographic quality. This approach offers tangible benefits for routine pharmaceutical quality control and supports broader implementation of sustainable, high-throughput analytical methods

Instrumentation Used

• Waters Alliance HPLC with 2489 UV/Visible detector
• ACQUITY UPLC system with PDA detector
• Waters XBridge Shield RP18 4.6 × 250 mm, 5 µm column
• ACQUITY UPLC BEH Shield RP18 2.1 × 75 mm, 1.7 µm column
• Waters Method Transfer Kits and Empower 2 CDS

References

1. Monson K. Mometasone Furoate Ointment. eMedTV, 2011
2. USP Monograph. Mometasone Furoate Ointment, USP33–NF28, Oct 2010–Jan 2011
3. Jones M.D. et al. Implementation of Methods Translation between LC Instrumentation. Waters Application Note 720003721EN, 2010