Green AQbD-based HPLC method for estimation of isosorbide dinitrate in bulk and wafers

Abstract

Isosorbide dinitrate (ISDN) is widely used in the management of cardiovascular disorders; however, conventional analytical methods often rely on extensive organic solvent consumption and lack systematic optimization, raising concerns regarding environmental sustainability and method robustness. To address these challenges, the study aimed to develop and validate a robust, eco-friendly high-performance liquid chromatography method for the quantitative estimation of ISDN in bulk drug and wafer using Analytical Quality by Design (AQbD) and Green Analytical Chemistry principles. The method was developed employing an AQbD framework and validated using an HPLC system equipped with a C18-column (150 mm × 4.6 mm, 5 µm). Chromatographic separation was achieved using methanol/water (39:61, v/v) as the mobile phase at a flow rate of 1.01 mL/min, with UV detection at 210 nm. Environmental sustainability was evaluated using multiple green analytical assessment tools. The developed method demonstrated excellent linearity (R2 = 0.9998), precision (%RSD <2%), and high sensitivity with limits of detection and quantification of 0.065 µg/mL and 0.197 µg/mL, respectively. Greenness assessment showed excellent environmental performance with AGREE, Eco- Scale, and BAGI scores of 0.82, 88, and 82.5, respectively. Hence, the proposed AQbD-driven green HPLC method provides a reliable, sensitive, and environmentally sustainable approach for routine ISDN analysis while minimizing analytical waste and solvent-related environmental impact.