Unspecified degradation impurities identification and characterization in bilastine and montelukast tablet formulations by using UPLC and LCMS/MS: Robustness by design expert and green assessment.

Abstract

Objectives: This study introduces a novel ultra-performance liquid chromatography (UPLC) method for the rapid, simple, and accurate detection of contaminants in bilastine (BLS) and montelukast (MTK) tablet formulations.

Material and methods: The separation of BLS impurity-A, BLS impurity-B, BLS, MTK impurity-A, MTK, and MTK impurity-B was achieved using an Acquity BEH C18 column (50×2.1mm, 1.7μm) under gradient eluent conditions. The mobile phases consisted of 0.1% triethylamine in water with the pH adjusted to 2.5 using orthophosphoric acid (mobile phase A) and acetonitrile (mobile phase B). The ratio of mobile phase A to B was 70:30 (v/v). The column flow rate was set at 0.2mL/min, and the photodiode array detector (PDA) was used to quantify the analytes. The detection wavelength was set to 224nm.

Results: In a runtime of just 20minutes, 13 analytes were successfully separated. The retention times for the target compounds and impurities were as follows: BLS impurity-A: 1509min, BLS impurity-B: 3435min, BLS: 5668min, MTK impurity-A: 8137min, MTK: 9784min, MTK impurity-B: 11,853min. The unspecified impurities in the degradation samples were detected at retention times of 2174, 2657, 3368, 4143, 8239, 11,722, and 12,436minutes, and were characterized using liquid chromatography-mass spectrometry (LC-MS).

Conclusion: The UPLC-based analytical method demonstrated in this study is an effective and efficient technique for the quantification of BLS, MTK, and their associated impurities in tablet formulations. This method has been validated in accordance with ICH Q2(R2) and USP <1225> guidelines.