Development of a pH-dependent homogeneous liquid-liquid extraction by cold-induced phase separation in acetonitrile/water mixtures for determination of quinolone residues in animal-derived foods

•A scheduled variable full scan strategy was used to enhance detection performance.•A pH-dependent HLLE procedure by cold-induced phase separation was proposed.•Limits of quantitation ranged from 0.028 to 0.192 μg/kg in animal-derived foods.•The method was successfully applied in real samples for analysis of quinolones. A simple extraction procedure coupled with liquid chromatography-Q Orbitrap high resolution mass spectrometry (LC-Q Orbitrap HRMS) for the determination of 19 quinolones in animal-derived foods (pork, fish, egg and milk) has been developed. Sample preparation is based on homogeneous liquid-liquid extraction at pH > 9 using water-miscible acetonitrile with cold-induced phase separation. The procedure allowed one-step enrichment and cleanup of all the 19 quinolones with different logP properties to lower aqueous phase, which eliminated the process of preconcentration and re-dissolution for sample solution. Furthermore, an adsorption phenomenon was observed between conventional borosilicate glass injection vials and most of quinolones. In detection analysis, a scheduled variable full scan strategy was performed to improve detection performance in Q Orbitrap HRMS. Under optimal conditions, a superior limit of quantitation (0.028–0.192 μg/kg) in animal-derived foods was achieved using this proposed method. Lastly, this method was validated and applied successfully in real samples.