A novel type V natural deep eutectic solvent with built-in pH-regulation for magnetic dispersive liquid-liquid microextraction of central nervous system drugs in plasma samples

Introduction This study proposes an alkaline natural deep eutectic solvent (ANADES)-based magnetic dispersive liquid-liquid microextraction (ANADES-M-DLLME) method for the convenient, green, and efficient extraction of CNS drugs from plasma. Methods A novel, non-toxic type V ANADES, serving as the extractant, not only allows for polarity customization, but also directly adjusts the solution’s pH to alkaline conditions due to its built-in pH regulation, significantly improving the extraction efficiency of CNS drugs. Moreover, the elimination of the external pH adjustment, combined with magnetic particle-assisted retrieval of the extractant, substantially streamlines the sample preparation process. Results Under the optimal extraction conditions, the developed method, coupled with GC-MS/MS detection, was successfully applied for the extraction and quantification of CNS drugs in human plasma samples. The validated method exhibited good linearity ( R 2 > 0.990), with high accuracy (spiked recoveries 95.1%–114.9%) and precision (RSDs < 13.3%). Low limits of detection (0.61–3.36 ng/mL) and quantification (2.05–9.89 ng/mL), satisfactory extraction recoveries (85.01%–99.89%), and enrichment factors (6.65–8.79) were achieved for the seven target analytes. The analysis of the proposed method using three green analytical chemistry metrics further substantiated the method's greenness. Discussion Compared with reported DLLME techniques, the established ANADES-M-DLLME method was green, rapid, convenient, and cost-effective, offering a promising solution for widespread clinical and bioanalytical applications.