A Novel Stability-Indicating Method for Determination of Related Substances of Montelukast Sodium in a Pharmaceutical Dosage Form Using RP-HPLC

The main aim is to develop a simple, rugged, and sensitive method for determining the Montelukast Sodium-related impurities in a tablet dosage form using reverse-phase high-performance liquid chromatography (RP-HPLC) method. Chromatographic separation on the Agilent Eclipse XDB C18 (octadecylsilane) column of the dimension (100 mm × 4.6 mm, 5 µm) was carried out in the gradient mode with triethylamine and acetonitrile in various combinations and adjusted to a pH of 6.60 using phosphoric acid. The mobile phase was pumped at a flow rate of 1.0 mL min−1 and the analyte was monitored with a UV detector at a wavelength of 220 nm. The method was developed and validated under the stress conditions such as acidic, basic, peroxide, thermal, photolytic, and humidity degradation, respectively. Under the above conditions, oxidative degradation was performed which served as the system suitability solution providing a resolution of 2.5 between the Impurity 3 (retention time = 13.8 min) and Montelukast Sodium (retention time = 24.2 min). The method was validated with respect to specificity, linearity, precision, accuracy, limit of detection, and limit of quantification provided by the ICH guidelines. Results of linear regression analysis of the calibration plot revealed a good linear relationship between response and concentration with a correlation coefficient value of r2 = 0.9999. The accuracy of known impurities was obtained in the range of 94–108%. From the analysis, their LOD and LOQ values for impurities were measured and found to be 0.007 and 0.025 μg g−1, respectively. Chromatographic interference was not found during the degradation and excipients were detected from the tablet. The proposed method was successfully used to estimate the Montelukast Sodium-related impurities in a tablet dosage form.