Analysis of Impurities in Montelukast

Importance of the Topic

Analysis of drug impurities is essential for ensuring pharmaceutical safety, efficacy and regulatory compliance. Montelukast, a widely used leukotriene receptor antagonist, requires rigorous impurity profiling to prevent adverse effects and to meet international quality standards.

Objectives and Study Overview

This study aims to develop a robust LC-MS method for simultaneous determination of Montelukast and its known impurities. The approach focuses on achieving clear separation, sensitive detection and reliable quantitation of five impurity species alongside the active pharmaceutical ingredient.

Methodology

The separation employed reversed-phase liquid chromatography on a phenyl stationary phase with a binary gradient of aqueous and organic modifiers containing formic acid. Key chromatographic parameters included:

• Column: Shim-pack Scepter Phenyl-120, 50 mm × 2.1 mm I.D., 1.9 µm
• Mobile phases A: water/formic acid (2000:3), B: acetonitrile/formic acid (2000:3)
• Gradient: 45 % B (0–3 min) → 65 % B (3–16 min) → 45 % B (16.1–25 min)
• Flow rate: 0.25 mL/min; Column temperature: 30 °C; Injection volume: 10 µL
• UV detection at 238 nm for preliminary monitoring

Instrumentation Used

• Liquid chromatograph: Nexera XR system
• Mass spectrometer: LCMS-2050 with ESI/APCI DUIS ionization in positive mode
• Gas flows: Nebulizing 3.0 L/min, Drying 5.0 L/min, Heating 7.0 L/min
• Temperatures: DL 250 °C, Desolvation 400 °C; Voltage: Interface 3.0 kV, Qarray 80 V
• Autosampler vials: 1.5 mL glass LabTotal for LC

Main Results and Discussion

The optimized method achieved baseline separation of Montelukast and five impurities, with retention time reproducibility within acceptable limits. UV detection provided initial peak identification while MS confirmed molecular ions and fragment patterns for each impurity. Mass spectra enabled specific assignment of impurity structures and assessment of their relative abundances.

Benefits and Practical Applications

The presented LC-MS protocol offers high sensitivity and selectivity for routine quality control of Montelukast formulations. Its short run time and robust performance facilitate impurity screening in research and industrial laboratories, supporting regulatory submissions and batch release testing.

Future Trends and Applications

Advances in high-resolution MS and automated data processing will further enhance impurity profiling, enabling trace-level quantitation and structural elucidation. Coupling with ultra-high-pressure LC and multimodal detection could accelerate method development and expand coverage for novel impurities.

Conclusion

The developed reversed-phase LC-MS method on a phenyl column demonstrates effective separation and reliable detection of Montelukast impurities. Its adoption in pharmaceutical workflows will improve product quality assurance and streamline compliance with regulatory requirements.

Reference

• Application News 01-00319 (JP, ENG), Shimadzu Corporation, First Edition: Sep. 2024