Synergistic Sugaring‐Out Microextraction Coupled With Synchronous Fluorescence for Multiplexed Diuretic Detection in Pharmaceuticals and Biofluids

An environmentally friendly approach was developed for the precise determination of bumetanide and amiloride, two diuretics with complementary therapeutic applications. The method employs an integrated sugaring-out homogeneous liquid-liquid microextraction (SULLME) technique in conjunction with synchronous fluorescence spectroscopy. This approach eliminates toxic organic solvents typically used in liquid-liquid extraction. The two drugs exhibit distinct synchronous fluorescence signatures at a Δλ of 140 nm, facilitating baseline-resolved signals and thereby reducing analysis time and costs. The method was linear for bumetanide (0.05-0.5 μg/mL) and amiloride (0.04-1.0 μg/mL). Additionally, it exhibits low limits of detection (LODs) of 0.006 and 0.012 μg/mL for bumetanide and amiloride, respectively, demonstrating high sensitivity. The approach was successfully applied for the determination of both drugs in coformulation with a challenging ratio and in spiked human urine. A multifaceted assessment that included performance, technique innovation, and sustainability measures was carried out to determine the approach's overall feasibility. By combining environmentally friendly sample preparation and low reagent usage, the proposed strategy adheres to green analytical chemistry principles while preserving good analytical performance. This study shows how advanced spectroscopic techniques combined with green chemistry concepts may produce high-performing, affordable, and ecologically friendly analytical solutions for pharmaceutical multianalyte monitoring.