High Speed Analysis of Pharmaceutical Impurities in Compliance with European Pharmacopoeia Using Nexera-i MT

Significance of the Topic

The drive toward faster liquid chromatography methods has become critical in pharmaceutical analysis for improving laboratory throughput while ensuring compliance with stringent regulatory standards. Ultra high performance liquid chromatography based approaches offer significant gains in efficiency and reduced solvent usage, aligning with both productivity goals and green chemistry initiatives.

Objectives and Study Overview

This study evaluates the potential to accelerate pharmacopeial methods for two drug substances, ivermectin and diclofenac sodium, by leveraging the flexibility permitted in the European Pharmacopoeia adjustment guidelines. It demonstrates how an integrated HPLC/UHPLC system can switch between conventional and high speed flows without revalidation when system suitability criteria are met.

Methodology and Instrumentation

The work employed the Nexera-i MT system featuring separate high performance and ultra high performance flow lines. Shim-pack GIST C18 columns were used in two configurations:

• Conventional analysis column 250 mm length, 4.6 mm internal diameter, 5 µm particles
• High speed analysis column 150 mm length, 4.6 mm internal diameter, 3 µm particles

The mobile phases comprised water, methanol and acetonitrile blends for ivermectin, and a sodium phosphate buffer with methanol for diclofenac sodium. UV detection at 254 nm was applied, with column temperature controlled at 25 °C and a 20 µL injection volume.

Main Results and Discussion

For ivermectin related substances, switching to UHPLC conditions reduced analysis time by about 60 percent and mobile phase consumption by 40 percent, while retaining clear separation of the H2B1a and H2B1b peaks. System suitability tests for resolution, signal-to-noise ratio and peak symmetry passed both modes.

For diclofenac sodium, high speed analysis shortened run time by roughly 70 percent and cut solvent use by 40 percent. Even with a modest reduction of conventional flow rate to address system pressure limits, both conventional and rapid methods met the European Pharmacopoeia criteria for resolution of impurity F relative to the main compound.

Benefits and Practical Applications

This approach enables laboratories to dramatically increase sample throughput and reduce resource consumption without extensive revalidation. By operating a single instrument in dual mode, analysts can maintain compliance with pharmacopoeial requirements while optimizing efficiency for routine quality control and impurity profiling.

Future Trends and Applications

Advances in column technology, smaller particle sizes and intelligent method development are expected to push analysis times even lower. Integration with automated systems and data analytics will further streamline workflows. The trend toward greener, solvent-saving workflows will drive wider adoption of high speed UHPLC in both regulated and research environments.

Conclusion

By exploiting allowable adjustments under the European Pharmacopoeia and utilizing an integrated HPLC/UHPLC platform, it is possible to achieve substantial gains in analysis speed and solvent economy. The methods maintain all required performance criteria, offering a practical route to boost laboratory productivity and sustainability.

Reference

European Pharmacopoeia 8.0 04/2009 2.2.46 Chromatographic separation techniques
European Pharmacopoeia 8.8 04/2016 Ivermectin section
European Pharmacopoeia 8.8 07/2014 Diclofenac sodium section