An eco-friendly HPLC method for the sustainable analysis of the newly approved combinations of Alfuzosin and Tamsulosin, with Tadalafil in organic-solvent-free mixed-micellar systems

Abstract

In 2019, 94.00 million prevalent cases of benign prostatic hyperplasia (BPH) were reported, accounting for 2.48% of the global population. BPH is a significant urological health concern worldwide, leading to considerable economic burdens. The European and American guidelines for lower urinary tract symptoms were recently updated in 2023/2024, supporting a combination therapy of alpha-1 blockers with phosphodiesterase-5 inhibitors. Moreover, patents describing this combination have been previously reported. In this work, a novel, totally green organic-solvent-free mixed-micellar liquid chromatography method was developed to simultaneously analyze alpha-1 blockers alfuzosin (ALF) and tamsulosin (TMS) and phosphodiesterase-5 inhibitor tadalafil (TAD). Response surface methodology was employed to optimize the critical chromatographic variables, and a design space representing the robustness zone was identified. Separation was achieved on an RP-C18 column (150 × 4.6 mm², 5 μm) using a green mixture of Brij-35 (19.91 mM), SDS (130.00 mM), and sodium dihydrogen phosphate buffer (10.00 mM) at pH 4.65. The flow rate was set at 1.5 mL min⁻¹, and UV detection was observed at 250, 285 and 214 nm for ALF, TAD and TMS, respectively. The method was validated over a concentration range of 5–100 μg mL⁻¹ for all drugs with detection limits of 0.77, 1.23 and 1.59 μg mL⁻¹ and quantification limits of 2.35, 3.73 and 4.82 μg mL⁻¹ for ALF, TAD and TMS, respectively. The method was applied to determine the content of the analytes in various tablets and other pharmaceutical products. Greenness of the method was assessed using the Analytical GREEnness metric approach (AGREE), and the blueness was assessed using blue applicability grade index (BAGI), with scores of 0.76 and 82.5, respectively. These scores underline the superiority of the proposed procedure over previously reported methods.