Chromatographic Assay of Dapsone Tablets Using the ACQUITY UPC2 System

Importance of the Topic

The analysis of dapsone in tablet formulations is critical in pharmaceutical quality control to ensure dosage accuracy, product efficacy, and patient safety. Transitioning from traditional normal phase HPLC to supercritical fluid chromatography (SFC) offers substantial environmental, operational, and economic advantages.

Objectives and Overview

This study aimed to convert the USP compendial normal phase HPLC assay for dapsone tablets to an SFC method using the ACQUITY UPC² System. Key goals included achieving equivalent or improved analytical performance, reducing analysis time, and minimizing organic solvent consumption.

Methodology

Preparation

• Standard and tablet sample solutions were prepared following the USP protocol.

Normal Phase HPLC Conditions

• Column: 4.0 × 300 mm, 10 μm silica
• Mobile Phase: n-hexane:isopropanol:acetonitrile:ethyl acetate (7:1:1:1)
• Flow Rate: 1.5 mL/min
• Run Time: ~12.5 min

SFC Conditions

• Column: ACQUITY UPC² BEH, 3.0 × 50 mm, 1.7 μm
• Temperature: 45°C
• Mobile Phase: CO2 (85%) with methanol modifier (15%)
• Flow Rate: 3.0 mL/min
• Back Pressure: 130 bar (1885 psi)
• Detection: UV/PDA at 254 nm

Instrumentation

ACQUITY UPC² System equipped with UV/PDA detector, equipped for supercritical fluid chromatography using CO2 delivery and methanol modifier.

Main Results and Discussion

Suitability

• Normal phase HPLC: RT %RSD <0.1%; peak area %RSD <1.1% (n=6)
• SFC (UPC²): RT %RSD 0.8%; peak area %RSD 0.9% (n=6)

Performance

• Run Time: 1.75 min (SFC) vs 12.5 min (HPLC)
• Solvent Usage: ~0.50 mL methanol (SFC) vs 18.9 mL total organic solvents (HPLC)
• Cost per Run: $0.01 (SFC) vs $1.08 (HPLC)

Results from both methods showed excellent agreement in assay values, confirming the validity of the SFC approach.

Benefits and Practical Applications

Switching to SFC provides:

• Significant reduction in hazardous solvent disposal and associated costs
• Accelerated sample throughput, enhancing laboratory productivity
• Lower operating expenses per analysis
• Improved environmental, health, and safety profiles

Future Trends and Potential Applications

Further adoption of UPC² systems is anticipated across pharmaceutical QA/QC for other compendial assays. Advances may include automated method translation software, expanded use of green solvents, and integration with high-throughput sample preparation.

Conclusion

The USP normal phase HPLC assay for dapsone tablets was successfully converted to an SFC method on the ACQUITY UPC² System, achieving faster analysis, reduced solvent consumption, and maintained or improved data quality. This demonstrates a viable path toward greener and more cost-effective chromatographic assays.

References

Waters Corporation. Chromatographic Assay of Dapsone Tablets Using the ACQUITY UPC² System. Application Note, February 2012.