Sustainable QbD-Driven RP-HPLC Method for the Simultaneous Estimation of Azelnidipine and Metoprolol Succinate with Green and Red Analytical Assessments

A sustainable, stability-indicating Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method was developed and validated for the simultaneous estimation of Azelnidipine (AZL) and Metoprolol Succinate (MET) using an Analytical Quality by Design (AQbD) approach. Method optimization was performed using Central Composite Design (CCD), focusing on critical method parameters including flow rate, mobile phase composition, and detection wavelength. The optimized method employed a C18 column with a mobile phase of acetonitrile: water (70:30, v/v) under gradient elution and detection at 230 nm. The method showed excellent linearity, accuracy, precision, and robustness across a defined concentration range and was confirmed to be stability-indicating through forced degradation studies. To assess the environmental and safety performance of the method, two modern evaluation tools were applied: Analytical Green Star Area (AGSA) and Rapid Assessment of Performance Indicators (RAPI). The AGSA tool confirmed strong adherence to the 12 Principles of Green Analytical Chemistry, while the RAPI score reflected high analytical reliability and occupational safety in line with Red Analytical Chemistry principles. The integration of QbD with green and red assessments ensures both regulatory compliance and sustainable laboratory practice. This validated method offers a practical and comprehensive solution for the routine quality control of AZL and MET in pharmaceutical formulations.