Analysis of real water samples with AQbD microextraction using thymol-based NADES: implications of uncontrolled...

The global burden of hypertension and its severe form, resistant hypertension, affecting up to 20% of 1.4 billion adults worldwide, drives mass consumption of multiple drugs. Consequently, antihypertensive agents from different classes enter aquatic environments, yet simultaneous extraction of such chemically diverse drugs remains challenging. This work developed a green analytical method for the simultaneous determination of three model antihypertensive agents from distinct classes, namely, furosemide, atenolol, and lisinopril, in water samples. The method employed dispersive liquid-liquid microextraction using a thymol-based natural deep eutectic solvent selected for its superior hydrophobicity and tunability across varying analyte polarities and acid-base characteristics. Extraction was optimized via Box-Behnken design, followed by HPLC-UV analysis on a phenyl column with gradient elution (detection at 220 nm). The validated method showed good linearity (furosemide: 2-100 µg L^-1, lisinopril: 5-100 µg L^-1, and atenolol: 0.1-50 µg L^-1) with LODs of 0.18, 0.66, and 0.031 µg L^-1, respectively. The practical applicability of the developed method was evaluated by analyzing real water samples collected from multiple sites across Egypt. The results revealed detectable concentrations of the target pharmaceuticals in several samples, confirming the presence of these contaminants in Egyptian water systems. Specifically, furosemide was detected at 4.72 µg L^-1, atenolol at 0.43 µg L^-1, and lisinopril at 7.21 µg L^-1 in samples collected from Giza. A comprehensive greenness assessment using the GAPI, AGREE, BAGI, and EVG tools confirmed strong alignment with sustainable chemistry principles. By enabling multi-class extraction of antihypertensive drugs with a low-ecological-footprint NADES-based protocol, this method addresses a critical gap as no prior NADES-based method exists for these three therapeutic classes together, supporting environmental monitoring and clean water objectives.