Sustainable Ethanol-Based Reversed-Phase Liquid Chromatography for Determination of Diltiazem pKa and Quantification...

This study presents a sustainable chromatographic method for the analysis of diltiazem. Retention behavior and the effect of mobile phase pH were investigated to determine the dissociation constant. Chromatographic experiments were performed at 37°C on a Gemini NX C18 column in binary mixtures of ethanol-water containing 40%, 45%, and 50% (v/v) ethanol and methanol-water containing 45%, 50%, and 55% (v/v) methanol. Using these retention data, the ${}_w^{w}p{K}_a$ value of diltiazem, which has low solubility in water, was calculated. Beyond analytical performance, the sustainability of method was evaluated multimetrically approach using the Environmental, Performance, and Practicality Index, the Carbon Footprint Reduction Index, and the Sustainability of Analytical Methods Index. This complementary framework provides a holistic assessment of operational greenness, carbon intensity, and global sustainability goals in accordance with the latest guidelines. The method for diltiazem determination according to these tools showed linearity with a correlation coefficient of 0.999 in the concentration range of 1.0-15 µg/mL and achieved acceptable precision and accuracy. Validated according to ICH Q2(R2) guidelines, the procedure was successfully applied to tablet formulations and forced degradation studies. This work establishes a comprehensive, ecofriendly methodological approach suitable for pharmaceutical analysis.