Related Impurities HPLC Method Development & Validation for drug combinations: Olmesartan Medoxomil, Chlorthalidone & Cilnidipine

Abstract

The LC-MS compatible, stability-indicating, specific, linear, accurate, sensitive with less run-time RP-HPLC related impurities method has been developed for Olmesartan Medoxomil, Chlorthalidone, and Cilnidipine drug combinations. And the method has been validated according to ICH and US-FDA guidelines. The separation was performed by using Hypersil-BDS Thermo-Scientific, C/18 (12.5 cm, 4.6mm, 5-micron particle size) column. Mobile phase-I was prepared by mixing 3.85 gm Ammonium acetate in HPLC water and adjust pH-5.0 by using diluted acetic acid. Acetonitrile was taken as Mobile phase-B. Initial mobile phase ratio (55:45,v/v) was adjusted for Mobile phase-A: Mobile phase-B followed by gradient program. Other chromatographic conditions such as column temperature 25 degrees, flow rate 1.0 mL/minutes with the detection wavelength at 260 nm. The retention time for Chlorthalidone Impurity A, Olmesartan, Olmesartan Medoxomil Impurity A, were found about 2.7, 3.3, and 7.2 minutes, with a total run time of 18.0 minutes. The linearity calibration plot was performed andfound linear relationship over the concentration range of 1.25(LOQ)–18.75 μg/ml, 3.6(LOQ)–60.0 μg/ml,3.6(LOQ)–60.0 μg/ml respectively for Chlorthalidone Impurity-A, Olmesartan and Olmesartan MedoxomilImpurity A respectively. The LOD and LOQ were found 0.4 ppm (μg/ml) & 1.2 ppm (μg/ml), 1.2 ppm (μg/ml) & 3.5 ppm (μg/ml), 1.1 ppm (μg/ml) & 3.3 ppm (μg/ml) for Chlorthalidone Impurity A, Olmesartanand Olmesartan Medoxomil Impurity A respectively. The accuracy was determined by recovery studies was found between 90.0-110.0%. The developed analytical method has been validated for lod-loq specificity, linearity, accuracy, precision, robustness, and ruggedness, which were well within the acceptance limit as per ICH guidelines. All the degradation products generated by stress conditions were found to be well separated from one another (all drug components and impurities). The developed method with shorter runtime was successfully implemented for routine quality control and stability analysis to checkthe quality of olmesartan medoxomil, chlorthalidone, and cilnidipine drug combinations.