Analysis of Montelukast Sodium Using Prominence-i and Nexera-i MT

Significance of the Topic

Reliable analysis of montelukast sodium is critical for ensuring safety and efficacy of asthma and allergic rhinitis therapies. Harmonized testing methods across the Japanese, US and European pharmacopoeias support global regulatory compliance and consistent product quality.

Objectives and Study Overview

This application note evaluates system suitability of montelukast sodium analysis using two Shimadzu liquid chromatography platforms: Prominence-i and Nexera-i MT. Tests are performed in accordance with the 17th edition of the Japanese Pharmacopoeia (JP), which aligns with USP and EP monographs.

Methodology and Used Instrumentation

The study follows the JP quantitative method leveraging a phenyl silyl silica gel column (50 × 4.6 mm, 1.8 µm), with a gradient mobile phase of aqueous and acetonitrile solutions containing trifluoroacetic acid. The flow rate is set at 1.2 mL/min, column temperature at 30 °C, and UV detection at 238 nm. Sample preparation involves a 1 mg/mL standard solution, aged for 20 minutes to generate impurity peaks.

• Prominence-i high-performance liquid chromatograph
• Nexera-i MT with HPLC and UHPLC channels

Main Results and Discussion

Both systems successfully resolved montelukast sodium from its related impurities (A–F). System suitability criteria were met as follows:

• Resolution between montelukast and Impurity B: ≥ 2.5 (observed 3.8)
• Resolution between montelukast and Impurity E: ≥ 1.5 (observed 2.8)
• Repeatability (RSD area) ≤ 0.73 % (observed 0.27 % on Prominence-i, 0.21 % on Nexera-i MT)

The ACTO function in the i-Series was used to correct gradient dwell volume differences, reducing retention time deviations from up to 3.1 % to below 0.3 % across all peaks.

Benefits and Practical Applications

The validated methods offer robust quality control for montelukast sodium, ensuring compliance with international pharmacopoeia standards. The rapid method transfer capability of Nexera-i MT accelerates lab workflows and supports multi-site harmonization.

Future Trends and Potential Applications

Advances in integrated LC platforms and automated method transfer tools will further streamline pharmacopeial testing. Expansion to UHPLC and hyphenated techniques (LC-MS) may enhance sensitivity for trace impurity profiling. AI-driven data analysis could optimize system suitability parameters in real time.

Conclusion

The study confirms that both Prominence-i and Nexera-i MT meet JP system suitability requirements for montelukast sodium analysis. Effective gradient correction via ACTO ensures consistent retention times, enabling reliable, harmonized testing across laboratories.

Reference

Shimadzu Application Note L520, July 2017.