Integrated Analytical Quality by Design (AQBD) Approach for the Development and Validation of Liquid Chromatography Method for Simultaneous Estimation of Rimantadine

Abstract

A simple, precise, and robust reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the estimation of Rimantadine in bulk and pharmaceutical dosage forms in accordance with ICH Q2(R1) guidelines. Method optimization confirmed that flow rate, buffer pH, and organic ratio significantly influenced chromatographic performance. The optimized method employed an Inspire C18 column (3.0 × 150 mm, 5 µm) with a mobile phase consisting of phosphate buffer (pH 3.0) and methanol, delivered at a flow rate of 1.0 mL/min, with detection at 265 nm. A sharp and symmetrical peak was obtained at a retention time of 6.12 min, with system suitability parameters meeting all acceptance limits (plate count >5800, tailing factor ~1.0).Validation studies demonstrated excellent linearity in the concentration range of 15–75 µg/mL (R²=0.9994), high precision with %RSD values below 0.2%, and accuracy with mean recoveries between 96.7–101.2%. The method was sensitive with LOD and LOQ values of 2.96 µg/mL and 9.97 µg/mL, respectively. Robustness testing confirmed that deliberate variations in flow rate and mobile phase composition did not significantly affect results. Overall, the developed RP-HPLC method is accurate, reproducible, cost-effective, and stability-indicating, making it highly suitable for routine quality control, batch release, and regulatory applications of Rimantadine formulations.