Extraction of highly hydrophilic compounds from biological fluids including urine or plasma samples is a
dilemma due to high hydrophilicity of the matrix itself. The main aim of the current work is to explore the
competence of ionic liquid (IL)-based surfactant-coated mineral oxide nanoparticles (NPs) in dispersive solidphase microextraction (d-SPME) of highly hydrophilic analytes taking cefoperazone (CPZ) as a model analyte for the study. The IL-based surfactant coated Fe3O4 NPs is utilized as an innovative adsorbent for the separation and pre-concentration of CPZ after intramuscular injection (I.M) in rabbits. The utilized magnetite NPs were synthesized via simple and reliable co-precipitation procedure, which doesn’t require any air-free environment and depends on a single iron (III) salt. Characterization of the as-synthesized NPs was achieved by X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR) and energy dispersive X-ray (EDX). Surface area measurements show that Fe3O4 NPs have large surface area of 75 m2 g- 1. The developed approach utilizes the unique properties of the IL-based surfactant including multiple polar interaction types provided by the polar head in addition to merits of Fe3O4 nanoparticles, which include large adsorptive capacity and magnetic properties, to improve separation, save time, and achieve satisfactory recovery. Comprehensive study was developed for the factors, that affect the adsorption capacity such as pH, NPs amount, IL-based surfactant concentration, ionic strength, adsorption time, and desorption conditions. Moreover, the adsorption data was fitted to Langmuir and second-order kinetic models as reflected by the reasonable determination coefficients of 0.9319 and 0.9726, respectively. Under the optimized conditions, the developed approach achieves good correlation coefficient of 0.9975, and 0.9981 over linearity range of 0.7–12.0 and 4.0–50.0 µg mL- 1 for both CPZ standard solutions and spiked rabbit plasma, respectively. It also provides good sensitivity expressed by the low values of limit of detection (LOD) of 0.2 and 1.2 µg mL- 1 and limit of quantitation (LOQ) of 0.7 and 4.0 µg mL- 1 for both the  standard solutions and spiked plasma, respectively. The developed approach was also applied successfully for monitoring CPZ in rabbit plasma samples with satisfactory recovery % (83–110). In addition, a detailed pharmacokinetic study is performed where pharmacokinetic parameters of CPZ in rabbit plasma samples were
calculated.