Ultra-High-Speed and Ultra-High-Resolution Analysis of Drug Analogs

Significance of the Topic

The separation of structurally related drug analogs is critical for quality control and regulatory compliance in pharmaceutical development. Ultra-high-resolution and ultra-high-speed chromatographic techniques enable efficient analysis of these compounds, ensuring accurate identification and quantitation.

Study Objectives and Overview

This application report examines the performance of the Shimadzu Nexera UHPLC system for analyzing ketoprofen and its structural analogs under three sets of chromatographic conditions: conventional, ultra-high-speed, and ultra-high-resolution. The goal was to demonstrate time savings and improved resolution while maintaining system robustness.

Methodology and Instrumentation

• Instrumentation: Shimadzu Nexera UHPLC system (130 MPa maximum pressure)
• Chromatographic conditions:
  • Conventional: ODS column (150 mm×4.6 mm I.D., 4.6 μm), flow rate 1.0 mL/min, 6.5 MPa
  • Ultra-high-speed: ODS column (50 mm×2.1 mm I.D., 1.8 μm), flow rate 0.8 mL/min, 50 MPa
  • Ultra-high-resolution: ODS column (250 mm×2.1 mm I.D., 1.8 μm), flow rate 0.5 mL/min, 118 MPa
• Mobile phase: 0.1 % formic acid in water/acetonitrile (65/35)
• Column temperature: 40 °C
• Detection: UV at 254 nm

Key Results and Discussion

• Ultra-high-speed analysis reduced total run time to approximately one tenth of the conventional method while preserving chromatographic resolution for ketoprofen and its analogs.
• Ultra-high-resolution conditions achieved baseline separation of closely eluting analogs that were not fully resolved under conventional settings.
• The high-pressure tolerance of the Nexera system (130 MPa) was essential for operating at 118 MPa during high-resolution runs.

Benefits and Practical Applications

• Significant reduction in analysis time supports high-throughput screening in quality control environments.
• Enhanced resolution improves the reliability of impurity profiling and trace-level quantitation in pharmaceutical assays.
• Flexibility to switch between speed and resolution modes allows adaptation to various analytical priorities.

Future Trends and Potential Applications

• Integration with mass spectrometric detectors for structural identification and quantitation at low concentration levels.
• Development of even higher pressure UHPLC systems and sub-1 μm particle technology for further resolution enhancement.
• Miniaturized and automated platforms for on-site pharmaceutical testing and process monitoring.

Conclusion

The Shimadzu Nexera UHPLC platform, coupled with sub-2 μm particle columns, enables both ultra-high-speed and ultra-high-resolution separation of ketoprofen analogs. This versatility delivers substantial time savings and superior chromatographic performance, meeting the stringent demands of pharmaceutical analysis.

Reference

• Shimadzu Corporation Application Data Sheet LAAN-A-LC-E242, December 2010