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

Importance of the Topic

Montelukast sodium is employed in the management of bronchial asthma and allergic rhinitis. Accurate quantification and detection of related impurities are critical for therapeutic safety and regulatory compliance. International harmonization across JP, USP and EP necessitates validated methods that yield consistent performance across different liquid chromatographs.

Objectives and Study Overview

This study evaluates system suitability tests for montelukast sodium in compliance with the 17th edition of the Japanese Pharmacopoeia using two Shimadzu systems: Prominence-i and Nexera-i MT. The work aims to demonstrate method robustness and to illustrate how the ACTO function facilitates method transfer with minimal retention time shifts between instruments.

Used Instrumentation

• Prominence-i high-performance liquid chromatograph
• Nexera-i MT integrated system with dual HPLC and UHPLC channels
• Phenyl silyl silica gel column (50 mm × 4.6 mm I.D., 1.8 µm)
• UV detector at 238 nm with cell temperature of 40 °C

Methodology and Analytical Conditions

Chromatographic separation employed a phenyl silyl silica gel column with a flow rate of 1.2 mL/min at 30 °C. The mobile phase consisted of (A) water/trifluoroacetic acid (2000/3, v/v) and (B) acetonitrile/trifluoroacetic acid (2000/3, v/v) under a linear gradient from 40% B to 51% B over 16 minutes. Sample solutions for system suitability were prepared by dissolving montelukast standard at 1 mg/mL, followed by equilibration to generate related substance peaks. A 10 µL injection volume was used for each run.

Main Results and Discussion

For both Prominence-i and Nexera-i MT, resolution between montelukast and key impurities exceeded pharmacopoeial requirements (>=2.5 for impurity B and >=1.5 for impurity E), with repeatability (RSD area) below 0.3%. Chromatograms showed clear separation of all listed related substances. When transferring the method to Nexera-i MT, initial retention time deviations up to ~3% were corrected using the ACTO gradient start time adjustment, reducing differences to below 0.3% across all peaks. This confirms the function’s effectiveness in compensating for system dwell volume and pump characteristics.

Benefits and Practical Applications

• Ensures pharmacopeial compliance through validated system suitability metrics
• Facilitates reliable interchange between HPLC platforms without extensive revalidation
• Enhances laboratory efficiency by automating gradient correction during method transfer
• Applicable to quality assurance, routine QC testing, and regulatory submissions

Future Trends and Potential Applications

Anticipated developments include broader adoption of integrated method transfer utilities, deeper coupling with mass spectrometry for impurity profiling, and expanded digitalization of QC workflows. Advanced control of system parameters may further streamline cross-platform harmonization for a wider range of pharmaceutically relevant compounds.

Conclusion

The study demonstrates that both Prominence-i and Nexera-i MT meet the Japanese Pharmacopoeia’s quantitative criteria for montelukast sodium analysis. The ACTO function effectively aligns retention times across instruments, supporting robust, transferable, and compliant HPLC methods in pharmaceutical analysis.