Development and validation of UPLC method for simultaneous quantification of carvedilol and ivabradine in the presence of degradation products using DoE concept |
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Authors: | Nukendra Prasad Nadella Venkata Nadh Ratnakaram N Srinivasu |
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Institution: | 1. Department of Science and Humanities, VFSTR, Vignan’s University, Guntur, Andhra Pradesh, India;2. AET Laboratories Pvt. Ltd, Kazipally Industrial Area, Hyderabad, Telangana, Indiaprasadnn14@gmail.com;4. Department of Chemistry, GITAM University, Bengaluru, Karnataka, India |
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Abstract: | A methodical design-of-experiments were performed by applying quality-by-design concepts to establish a design-space for simultaneous and rapid quantification of Carvedilol and Ivabradine by UPLC in the presence of degradation products. Response-surface, central-composite design, and quadratic model were employed for statistical assessment of experimental data using the Design-Expert software. Response variables such as resolution and retention time were analyzed statistically for chromatographic screening. During DoE study, various plots such as perturbation, contour, 3D and design-space plots were considered for method optimization. The method was developed using C8 100?×?2.1?mm, 1.8?µ] UPLC column, mobile phase comprising 0.5% triethylamine buffer pH 6.4] and acetonitrile in the ratio of 50:50 v/v, the flow rate of 0.4?mL minute?1 and UV detection at 285?nm for both Carvedilol and Ivabradine. The method was developed with a short run time of two minutes. The method was found to be linear in the range of 25.0–199.9?µg?mL?1 and 8.9–21.3?µg?mL?1 for Carvedilol and Ivabradine, respectively with a correlation coefficient of 0.9998 in each case. The recovery values were found in the range of 99.7–100.8% and 98.9–100.9% for Carvedilol and Ivabradine, respectively. The method was validated according to ICH Q2 (R1) guidelines. |
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Keywords: | Assay carvedilol and ivabradine design of experiments ICH validation UPLC |
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