QbD Engineered Paradigm for Development and Validation of Robust RP-HPLC Method for Analysis of Clopidogrel and Rosuvastatin from Solid Oral Dosage Form

Abstract

A robust, accurate, and Quality by Design (QbD)-driven RP-HPLC method was developed and validated for the simultaneous estimation of rosuvastatin calcium and clopidogrel hydrogen sulphate in fixed-dose combination tablets. Method development employed a Box–Behnken design to systematically optimize critical parameters detection wavelength, mobile phase pH, and flow rate targeting key chromatographic responses such as retention time, resolution, theoretical plates, and peak symmetry. The final method used a Prontosil C18 column (250 mm × 4.6 mm, 5 μm) with a mobile phase of methanol: acetonitrile: water (80:10:10 v/v), at a flow rate of 1 mL/min and detection at 225 nm. Retention times were found to be 3.225 min for rosuvastatin and 5.725 min for clopidogrel, with satisfactory resolution of 12.59 and good peak symmetry. The method showed excellent linearity over the range 3.75–300 µg/mL, with correlation coefficients of 0.9975 and 0.9992, respectively. Validation in line with ICH Q2 (R2) guidelines confirmed precision (%RSD < 2), accuracy (recoveries 99.31–100.28%), robustness, and specificity. Limits of detection and quantification were 0.35 µg/mL and 1.09 µg/mL for rosuvastatin, and 0.44 µg/mL and 1.34 µg/mL for clopidogrel, respectively. This risk-based approach established a reliable method for routine quality control, enhancing product quality and patient safety.