A Review on RP-HPLC Method Development and Validation of Bilastine and Montelukast in Bulk and its Dosage Form

Abstract

Bilastine, a second-generation antihistamine, is recognized for its effectiveness and favorable tolerability in treating allergic rhinitis and chronic urticaria. It offers a safety profile similar to other second-generation antihistamines, such as levocetirizine and desloratadine, but with significantly less sedation when compared to cetirizine due to its inability to cross the blood-brain barrier readily. Montelukast has been reviewed as an effective treatment for controlling symptoms associated with allergic rhinitis and asthma. However, its efficacy when compared to other treatments such as inhaled corticosteroids varies significantly. A major concern regarding montelukast is its potential for serious neuropsychiatric side effects, leading to the issuance of a black box warning by the FDA in 2020. This alert highlights an increased risk of mood alterations, behavioral changes, and cognitive issues, including suicidal ideation. Therefore, patients need to thoroughly evaluate the benefits against these potential risks and communicate any observed changes to their healthcare provider. The future of RP-HPLC method development and validation for the analysis of Bilastine and Montelukast in both bulk and dosage forms is marked by several pivotal trends and advancements. Key among these is the shift towards Ultra-High Performance Liquid Chromatography (UHPLC) or Ultra-Performance Liquid Chromatography (UPLC), which utilize smaller particle size columns, enhancing analytical speed, sensitivity, and resolution while also reducing solvent consumption. Further developments will be guided by the Quality by Design (QbD) framework, a proactive and systematic approach that emphasizes a comprehensive understanding of key parameters. This methodology aims to create robust analytical methods from the beginning, rather than relying on adjustments after the development phase. There is also a strong focus on developing highly selective stability-indicating methods (SIMs) that can effectively separate and measure active ingredients from their degradation products and impurities across various stress conditions, including acid/base hydrolysis, oxidation, thermal, and photolytic stress. In conclusion, the analytical methods for Bilastine and Montelukast are set to advance significantly, moving towards faster, more efficient, and environmentally friendly protocols that leverage technology to enhance data management and regulatory conformity.

Introduction

Bilastine is a second-generation antihistamine used to treat allergic rhinitis and chronic urticaria. It is effective, well-tolerated, and causes minimal sedation because it does not readily cross the blood–brain barrier. Clinical studies show rapid symptom relief, improved quality of life, and a low incidence of adverse effects, mainly mild headaches. Bilastine is also cardiologically safe and suitable for long-term use, though additional real-world studies are recommended. It should be taken on an empty stomach due to reduced absorption with food.

Montelukast is used to manage allergic rhinitis and asthma, showing better efficacy than placebo and comparable effectiveness to antihistamines, though less effective than intranasal corticosteroids. In pediatric asthma, it is useful but generally inferior to inhaled corticosteroids. Combination therapy can improve outcomes. Major concerns involve neuropsychiatric side effects—including mood changes and suicidal ideation—which prompted an FDA black box warning, making close monitoring essential.

The review also summarizes extensive research on developing and validating analytical methods—primarily RP-HPLC, UPLC, HPTLC, and LC-MS/MS—for simultaneous estimation of bilastine and montelukast in bulk and dosage forms. Various studies report precise, accurate, sensitive, and cost-effective chromatographic methods following ICH guidelines. They differ in mobile phase composition, columns, wavelengths, retention times, and validation outcomes, but consistently demonstrate strong linearity, low detection limits, robust recovery, and suitability for routine quality control. Several works include forced degradation studies and impurity profiling, with advanced methods incorporating Quality by Design (QbD) and LC-MS characterization.

Future trends include shifting toward UPLC/UHPLC technologies for faster and more sensitive analyses, broader adoption of QbD-based method development, enhanced stability-indicating methods, and increased integration of LC-MS/MS for impurity identification. Automation, AI-driven optimization, miniaturized LC systems, and environmentally sustainable (green chemistry) approaches are expected to further improve analytical efficiency, precision, and regulatory compliance.

Conclusion

In conclusion, the analysis of Bilastine and Montelukast is poised to evolve towards methodologies that are faster, more efficient, environmentally friendly, and highly specific, harnessing advanced technologies to improve data management and ensure regulatory compliance.

References

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Copyright

Copyright © 2025 Vaishnavi Khushalrao Jadhao, Ravindra H. Kale, Kailash R. Biyani. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.