Investigation of the ultrasound effect and target analyte selectivity of dispersive liquid–liquid microextraction and its application to a quinocetone pharmacokinetic study

An ultrasound-assisted dispersive liquid–liquid microextraction (UADLLME) was developed as a simple, sensitive, and robust method for the simultaneous determination of quinocetone (QCT) and three of its synthesized desoxy metabolites in swine urine samples via high-performance liquid chromatography (HPLC). Experimental parameters were optimized using the one-factor-at-a-time approach and were followed using an orthogonal array design. The results indicate that ultrasonic irradiation significantly affects the DLLME extraction efficiency. Moreover, the intermolecular binding energies and octanol–water partition ratio (Kow) of the target analytes were calculated using the density functional theory and the atom-additive method, respectively. A high correlation was found between the extraction efficiency and the calculated results, which may serve as a scientific guideline in the determination of the target analyte selectivity of DLLME. The feasibility of UADLLME with HPLC for the simultaneous determination of QCT and its desoxy metabolites in blank swine urine samples was then investigated. Higher enrichment factors (118–175), low limits of detection (0.06–0.12 ng mL−1), and high precisions (relative standard deviation < 2.5%) were obtained. Calibration curves were performed in the 0.5–500 ng mL−1 range and displayed good linearity. In addition, the proposed method was successfully applied to the pharmacokinetic study of QCT and its desoxy metabolites in real urine samples. The results show that UADLLME has a potential application in the pharmacokinetic and residue studies of quinoxaline-N-dioxides derivatives in biological fluid samples.