Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists

H2 receptor antagonists are often preferred in the treatment of gastroesophageal reflux disease or gastric acidity disorders. In this study, an HPLC method for the simultaneous chromatographic separation of H2 receptor antagonists, famotidine, nizatidine, ranitidine, and cimetidine active ingredients was developed by implementing green analytical chemistry principles and a chemometric approach. Chromatographic parameters, including ethanol ratio, buffer concentration, flow rate, and column temperature, were optimized using a DoE strategy. This green HPLC method's system compatibility, specificity, sensitivity, linearity, accuracy, precision, recovery, stability, robustness, and consistency parameters were validated only for the analysis of famotidine in the pharmaceutical preparation. The linearity range was 1.5-75 µg/mL, LOD was 0.5 µg/mL, and LOQ was 1.5 µg/mL. Afterward, the method specified in the USP monograph for Famotidine tablets was validated by examining the same parameters. The linearity range of this method was 5.0-500 µg/mL, the LOD was 2.0 µg/mL, and the LOQ was 5.0 µg/mL. Cimetidine was chosen as the internal standard (IS) in both methods, and the performance of the methods with and without IS was compared. Validation results showed that the developed method for the famotidine analysis was sensitive, precise, accurate, specific, robust, and consistent. In addition, validated methods were successfully applied to analyze the famotidine-containing pharmaceutical preparation. No statistically significant difference was found between the results. The developed methods, both with and without IS, exhibited lower LOD and LOQ values than the method specified in the USP monograph, while reducing the potential environmental and health hazards associated with the analytical procedure.