Atomoxetine, venlafaxine, and duloxetine are three antidepressant drugs widely prescribed to treat this disorder.Determining these drugs is a major challenge due to their low concentration and high matrix effects on biol. samples.Dispersive micro solid phase extraction was developed as a sample preparation strategy to extract these drugs in real water and biol. samples.A novel sorbent containing a magnetic MOF-on-MOF was prepared to extract these drugs using Fe3O4 nanoparticle and Sol-gel technique.The microextraction procedure was optimized under two steps using exptl. design.Three factors, including pH, sorbent amount, and desorption solvent volume, significantly affected the extraction of analytes and optimized using a central composite design.The optimum value of pH, sorbent amount, and desorption solvent volume was 29 mg, 6.5, and 150 μL.Under optimum conditions, the linear ranges for measuring atomoxetine, venlafaxine, and duloxetine in water samples were 1.42-496, 0.43-472, and 0.73-459 ng mL-1, resp.The detection limits of atomoxetine, venlafaxine, and duloxetine were 0.4, 0.1, and 0.2 ng mL-1.High and proper preconcentration factors ranged from 462.4-511.4 in distiled water samples and 450.7-489.8 in urine samples were obtained to determine atomoxetine, venlafaxine, and duloxetine with three concentrations of 5.0, 20.0, and 100.0 ng mL-1, resp.Inter-day and intra-day RSD% were calculated by triplicate determination of atomoxetine, venlafaxine, and duloxetine at three concentrations of 10.0, 50.0 and 100.0 ng mL-1 and were between 3.2-4.3% and 3.8-4.6% in distiled water samples, and 4.8-5.7% and 5.0-5.8% in urine samples, resp.Anal. of tap, river water, and two urine samples as real water and biol. samples under optimum conditions exhibited recovery and standard deviation in the ranges of 90.2-96.9% and 3.84-5.74%, resp., confirmed the proper ability of the method to determine atomoxetine, venlafaxine, and duloxetine in natural water and biol. samples.