AQbD-driven RP-HPLC method for complete resolution of pantoprazole regioisomeric impurities with integrated...

Pantoprazole is a widely prescribed proton pump inhibitor, and accurate control of its related substances is essential to ensure drug quality and patient safety. However, existing pharmacopeial and reported chromatographic methods often fail to achieve adequate resolution between the critical regioisomeric impurities D and F, resulting in their co-quantification. This study aimed to develop a robust, stability-indicating, and environmentally responsible RP-HPLC method for the simultaneous determination of pantoprazole and its six related substances. A systematic quality-by-design approach was employed, integrating risk assessment and Central Composite Design to optimize critical chromatographic parameters. The optimized method achieved complete baseline separation of all impurities, including the challenging D/F regioisomeric pair, with resolution values greater than 2.0 and a total runtime of less than 12 min. Method validation, performed in accordance with ICH Q2(R2), demonstrated satisfactory accuracy (recoveries of 96.8-99.7%), precision (%RSD < 2.0%), and excellent linearity (r > 0.998). The environmental and operational sustainability of the method was confirmed using multiple assessment tools, including AGREE, MoGAPI, BAGI, RAPI and RGB12, indicating a favorable greenness and overall performance profile. Overall, the proposed method provides a reliable, efficient, and sustainable analytical solution for routine impurity profiling of pantoprazole, with improved selectivity and robustness compared to existing methods, supporting its application in pharmaceutical quality control and regulatory settings.