Analysis of Lisinopril by LC/UV Using a Core Enhanced Technology Accucore RP-MS Column

Significance of the Topic

Lisinopril is an angiotensin-converting enzyme inhibitor widely used in hypertension management. Accurate and efficient analysis of lisinopril and its impurities is essential for pharmaceutical quality control to ensure patient safety and compliance with pharmacopeial standards.

Objectives and Study Overview

This application note illustrates how to adapt the USP monograph method for lisinopril to a shorter, high-efficiency format. The goal was to scale down the original column dimensions while maintaining required resolution between lisinopril and related impurities, and to improve sample throughput using a core-enhanced superficially porous column.

Methodology and Instrumentation

The method transfer employed a calculator to adjust flow rate and gradient for a 100×2.1 mm Accucore RP-MS column packed with 2.6 µm core-shell particles. Sample preparation involved diluting a standard lisinopril solution in mobile phase A. Chromatographic conditions included:

• Mobile phase A: 0.026 M sodium phosphate buffer, pH 3.75
• Mobile phase B: 80% A / 20% acetonitrile
• Gradient: 3% B to 30% B over 15 min, hold then re-equilibrate to 3% B at 35 min
• Flow rate: 0.4 mL/min
• Column temperature: 50 °C
• Detection: UV at 210 nm

Used Instrumentation

• Thermo Scientific Accucore RP-MS 2.6 µm, 100×2.1 mm column
• Thermo Scientific HPLC system with 15 µL UV flow cell
• ChromQuest 5.0 data acquisition software

Main Results and Discussion

Scaling down from a 250×4.6 mm 5 µm column to a 100×2.1 mm 2.6 µm Accucore RP-MS column delivered high efficiency and sufficient resolution for:

• Impurity 1 vs. 2-amino-4-phenylbutyric acid (resolution >4.6)
• 2-amino-4-phenylbutyric acid vs. lisinopril (resolution >12.7)
• Lisinopril vs. R,S,S-isomer (resolution >4.7)

Precision data (%RSD) for six injections showed values below pharmacopeial limits (1.7% for lisinopril). Reduced analysis time and lower backpressure were achieved due to the core-shell particle design.

Benefits and Practical Applications

The adaptation offers:

• Higher sample throughput via shorter run times
• Robust peak shapes with minimal tailing
• Lower system backpressure compared to sub-2 µm fully porous materials
• Compliance with USP resolution and precision criteria

Future Trends and Potential Applications

Advances in superficially porous particle technology will continue to drive method miniaturization and speed. Further integration with mass spectrometry and automated method transfer tools can expand applicability to other small-molecule drugs and impurity profiling in regulated environments.

Conclusion

The Accucore RP-MS column successfully scaled down the USP lisinopril method, offering high efficiency, excellent reproducibility, and faster analysis. This approach is recommended for laboratories seeking to enhance throughput while maintaining quality standards.

References

1. http://www.hplctransfer.com/
2. USP Monograph for lisinopril