In the present work, an efficient and environmental friendly method of ionic‐liquid‐based emulsified microextraction procedure accelerated by ultrasound radiation has been developed. Subsequently, its performance was compared with dispersive liquid–liquid microextraction and ultrasound‐assisted surfactant‐based emulsification microextraction methods. The optimization of experimental conditions was carried out by combination of central composite design and response surface methodology. The optimum conditions of variables were set as follows: 50 μL of 1‐hexyl‐3‐methylimidazolium hexafluorophosphate (extracting solvent), 10 min ultrasound time, and 10 min vortex time for agitating 6 mL sample solution in pH 3 in the presence of 4 mg sodium dodecyl sulfate without addition of salt and 200 μL of methanol as diluent solvent. Under these conditions, the responses are linear for doxepin and perphenazine in the range of 0.3–1000 and 5–1000 μg/L, respectively. The limits of detection were 0.1 μg/L for doxepin and 1 μg/L for perphenazine. Relative standard deviations were lower than 3.5 for the determination of both species. Finally, the method was used for the preconcentration and determination of doxepin and perphenazine in urine sample with relative recoveries in the range of 89–98%.
