Natural hydrophobic deep eutectic solvent for vortex-assisted dispersive liquid–liquid microextraction of anti-prostate cancer triple therapy from water and human plasma

Abstract

A green vortex-assisted dispersive liquid–liquid microextraction (VA-DLLME) method based on a hydrophobic natural deep eutectic solvent (NaDES) was developed and applied for the preconcentration of anti-prostate cancer triple therapy (flutamide, resveratrol, and ethynylestradiol) from river water and spiked human plasma for the first time. A hydrophobic NaDES based on α-terpineol and octanoic acid was prepared in a molar ratio of 1:1 and applied as an extracting solvent. High-performance liquid chromatography with a photodiode array detector (HPLC-PDA), coupled with a core–shell-based column was used for the final analysis. The significant factors affecting the extraction efficiency were optimized by means of a systematic methodology of one-variable-at-a-time (OVAT) followed by experimental design. The optimal extraction conditions were as follows: 400 μL of DES, vortex time of 50 sec, pH 2.5, and 3 % of NaCl. Under optimal conditions, the method was validated through matrix-matched calibration, limits of detection and quantitation, accuracy, and precision studies. The method exhibited excellent linearity (r2 > 0.999) over a range of 1–30 μg/L for ethynylestradiol and 0.5–30 μg/L for both flutamide and resveratrol with % relative standard deviation (%RSD) values ≤ 4.87 %. The method was successfully applied for the analysis of the concerned drugs in spiked human plasma and river water samples. Finally, the procedure's greenness was assessed using three various greenness metrics which confirmed its greenness and safety.