UPLC quantification of carvedilol and ivabradine using DoE concept

What is it about?

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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Why is it important?

The UPLC method was developed based on the design-ofexperiments approach for simultaneous, rapid quantification of Carvedilol and Ivabradine in the bulk and pharmaceutical drug products. The developed method was validated as per international council for harmonization guideline ICH Q2 (R1) validation of analytical procedures. The method was found to be simple, selective, accurate, precise and robust. The developed method was stability indicating as it was showing no interference of degradation products and placebo at the retention time of Carvedilol and Ivabradine. Due to the shorter run time of two minutes, this method provides faster analysis, more work throughput and reduces the cost of analysis due to the reduction in solvent consumption. Therefore, the developed method can be used for routine assay analysis of quality control samples and stability samples of bulk and finished pharmaceutical dosage forms.