Development of eco-friendly UPLC methods for metformin and empagliflozin by combining green chemistry with analytical quality by design

Abstract The need to develop environmentally friendly analytical approaches has driven the pharmaceutical industry to seek greener alternatives. Ultra-Performance Liquid Chromatography (UPLC) is known for its efficiency but traditionally relies on toxic solvents. Integrating Green Analytical Chemistry (GAC) principles aims to address environmental concerns while maintaining analytical performance. This work aims to advance and authenticate a green, efficient UPLC method for the concurrent quantification of Metformin (MET) and Empagliflozin (EPI) in tablet formulations, adhering to green chemistry principles and ensuring high analytical accuracy. The method was optimized using a UPLC-PDA system with a phenyl column and a mobile phase of ethanol and perchloric acid. Analytical Quality by Design (AQbD) was employed to optimize critical method parameters. Environmental impact was assessed using metrics such as GAPI, AMGS, and AGREE. Degradation studies under various stress conditions were performed to test method robustness. The method achieved high recovery rates for MET and EPI, with minimal interference from excipients. The environmental evaluation showed a high Analytical Eco-Score (AES) of 97, indicating low environmental impact. The AGREE score of 0.89 confirmed excellent alignment with green chemistry principles. Degradation studies confirmed the method's stability and reliability under stress conditions. The developed UPLC method demonstrates a significant advancement in analytical sustainability, offering an eco-friendly, efficient, and precise approach to drug analysis. The method's high alignment with green chemistry principles and its effectiveness in quantifying MET and EPI highlight its potential as a model for sustainable analytical practices in pharmaceutical analysis.