Development and validation of a QbD-integrated sensitive RP-HPLC method for quantitation of fenofibrate: an application in quality control

Abstract

Aim: The present study aims to develop and validate a robust, sensitive HPLC method for the estimation of fenofibrate in a gel-matrix sustained-release tablet formulation designed to prevent alcohol-induced dose dumping. Method: A simple, sensitive, and robust RP-HPLC method for fenofibrate was developed using a quality by design approach with a Box–Behnken design to optimise critical chromatographic variables and define a reliable design space. The method was validated as per the International Council for Harmonisation Q2 (R1) guidelines. Analysis was performed on a Shimadzu HPLC system with a PDA detector, binary pump, and column oven. Optimised conditions include a 70 : 30 (acetonitrile : water, pH 2.5) mobile phase, a flow rate of 1.2 mL min⁻¹, a C18 column (150 mm × 4.6 mm), an 8 min runtime, a sample temperature of 4 °C, and a column temperature of 40 ± 2 °C. The method was applied to sustained-release fenofibrate formulations to evaluate blend uniformity, content uniformity, assay, and dissolution under alcohol-induced dose-dumping conditions. Results: The developed method was found to be specific and sensitive, with low limits of detection and quantitation, and linear (R² = 0.999) over the concentration range of 5 µg mL⁻¹–80 µg mL⁻¹. The λ_max of fenofibrate was recorded at 285 ± 2 nm. Compared to previously reported RP-HPLC methods (LOD: 0.14–0.9 µg mL⁻¹; LOQ: 0.45–2.7 µg mL⁻¹), the developed method demonstrated significantly improved sensitivity (LOD: 0.0438 µg mL⁻¹; LOQ: 0.132 µg mL⁻¹) and reduced retention time (∼4.5 min vs. 6–20 min), indicating enhanced analytical efficiency. The obtained results fall within the acceptance limits. Conclusion: Our findings revealed that the developed RP-HPLC method is sensitive and robust. Hence this method can be used for the quantification of fenofibrate for dose dumping study, particularly in sustained-release (SR) tablet formulation.