Eco‐Friendly RP‐HPLC Method for Simultaneous Estimation of Amlodipine Besylate and Indapamide: Analytical Quality by Design Approach and Greenness Assessment

ABSTRACT This study presents the development and validation of an RP‐HPLC method for simultaneously estimating amlodipine besylate and indapamide using an Analytical Quality by Design (AQbD) approach. The Box–Behnken design optimized critical chromatographic parameters, emphasizing robust separation and minimal environmental impact. Methanol ratio and pH were systematically evaluated using response surface methodology to maximize the resolution and tailing factors of drugs. The chromatographic analysis utilized a Shimpack C18 column (250 × 4.6 mm, 5 µm) with a mobile phase of methanol and phosphate buffer (pH 4.5, adjusted with OPA) in a 45:55 ratio. Retention times were 2.69 min for amlodipine besylate and 10.07 min for indapamide. The method was validated per ICH Q2(R1) guidelines, demonstrating linearity in 0.25–8 µg/mL for indapamide and 0.75–24 µg/mL for amlodipine besylate. Greenness assessment using the analytical eco‐scale and AGREE software yielded scores of 87 and 0.61, respectively, highlighting reduced solvent consumption and environmental compliance. This eco‐friendly method aligns with green chemistry principles and supports routine pharmaceutical quality control, ensuring regulatory and environmental standards are met. This work highlights the integration of AQbD and green analytical chemistry for developing robust, sustainable, and reliable analytical methods.