Analysis of Irbesartan Using an Integrated LC System - NexeraTM-i MT

Significance of the Topic

High performance liquid chromatography methods specified in pharmacopoeias often rely on ultra-high performance columns, which are not widely adopted in quality control laboratories. Developing reliable transfer procedures from UHPLC to conventional HPLC expands accessibility and ensures compliance with official monographs in manufacturing settings.

Objectives and Study Overview

This study demonstrates a workflow for transferring the quantitative analysis of irbesartan in combination tablets with amlodipine besilate from UHPLC conditions listed in the Japanese Pharmacopoeia to conventional HPLC settings. The aim is to establish system suitability and validate performance using a dual-path integrated LC system.

Methodology and Instrumentation

An integrated NexeraTM-i MT system equipped with independent UHPLC and HPLC flow paths was used. Method parameters included:

• UHPLC path: Shim-pack XR-ODSII column, 75 × 3.0 mm, 2.2 µm; mobile phase methanol/0.02 mmol/L sodium phosphate buffer pH 3.0 (3:2); flow rate 0.8 mL/min; column temp. 40 °C; injection volume 5 µL; detection UV at 237 nm.
• HPLC path: Shim-pack VP-ODS column, 150 × 4.6 mm, 5.0 µm; mobile phase and temperature matched; flow rate adjusted to 1.0 mL/min; injection volume 10 µL.

System suitability tests were performed according to JP criteria, evaluating resolution between peaks and relative standard deviation of peak areas (n=6).

Main Results and Discussion

Under UHPLC conditions, resolution between amlodipine besilate and irbesartan exceeded 14 and RSD was 0.145%, both passing JP requirements. Transfer calculations based on column dimensions and particle size yielded a recommended flow rate of ~0.83 mL/min; a practical rate of 1.0 mL/min was used within a ±50% allowable adjustment. The HPLC method produced a resolution of 13.9 and RSD of 0.212%, demonstrating satisfactory performance without full revalidation.

Benefits and Practical Applications

The approach enables quality control laboratories equipped with conventional HPLC to adopt compendial methods originally specified for UHPLC. It streamlines method transfer, reduces the need for specialized instrumentation, and aligns with international harmonization efforts across pharmacopeias.

Future Trends and Potential Applications

Ongoing efforts toward global harmonization of allowable method adjustments will facilitate broader adoption of transfer guidelines. Integrated systems offering dual UHPLC/HPLC capabilities may become standard, and automated tools for method conversion are likely to emerge, improving efficiency in regulated laboratories.

Conclusion

Method transfer from UHPLC to HPLC using an integrated system has been validated through system suitability testing and meets JP criteria for irbesartan and amlodipine besilate analysis. This strategy offers a practical solution for compliance in manufacturing quality control.

References

• Strategic Directions International, Inc. Ultra-High Performance Liquid Chromatography (UHPLC), May 2016.
• Japanese Pharmacopoeia Supplement 1 to the 17th Edition, 42-44.
• Proposal for International Harmonization (Stage 4), Pharmaceuticals and Medical Devices Agency, July 2017.