The applicability of magnetic nanoparticles (MNPs) coated with cetyltrimethylammonium bromide (CTAB) as a cationic surfactant was evaluated for the extraction and preconcentration of four antidepressant drugs (amitriptyline, nortriptyline, imipramine, and doxepin) before their determination by high-performance liquid chromatography with UV detection (HPLC-UV). Mixed hemimicelles formed on the surface of MNPs by CTAB showed great adsorptive tendency toward the analytes. The main factors influencing the extraction efficiency including pH, amount of surfactant, ionic strength, shaking time, and desorption ability of organic solvents were investigated and optimized. Under the optimized conditions, preconcentration factors up to 250 were achieved and the relative standard deviation (RSD %) of the method was in the range of 4-8 %. The calibration curves were obtained in the range of 10-400 mu g L-1 with reasonable linearity (R (2) > 0.99) and the limits of detection (LODs) ranged between 3 and 5 mu g L-1 (based on S/N = 3). Finally, the applicability of the proposed method was evaluated by extraction and determination of the drugs in urine and water samples. The results indicated that CTAB-MNPs method has excellent clean up and high pre-concentration factor and can be served as a simple and sensitive method for monitoring of antidepressant drugs in the urine and water samples.