A new type of liquid-phase microextraction based on two immiscible organic solvents was optimized and validated for the quantification of lidocaine, ketamine, and cocaine in human urine samples. A hollow-fiber based microextraction technique followed by gas chromatography coupled with mass spectrometry detection was used to reduce matrix interferences and improve limits of detection. The analytes were extracted from aqueous sample with pH 11.0, into a thin layer of organic solvent (n-dodecane) sustained in the pores of a hollow fiber, and then into a second organic acceptor (acetonitrile) located inside the lumen of the hollow fiber. With the application of optimized values, good linearity was obtained in the range of 1-500 μg/L for lidocaine and ketamine and 2-500 μg/L for cocaine with the determination coefficient values (r(2) ) >0.9943. The preconcentration factors and limits of detection (S/N > 3) were 250-350 and 0.01-0.05 μg/L, respectively. Intra and interassay precision values were <7.3 and 9.3%, respectively. The method was successfully applied for the determination and quantification of target analytes in human urine samples.