Fluoxetine (N-methyl-c-[4-phenoxy] benzene epropanamine) (FLU) is the parent drug of the selective serotonin reuptake inhibitor (SSRI) antidepressant class, which has emerged as a major therapeutic advance in psychopharmacology. It has been approved worldwide in the therapy of major depression and has also demonstrated to be effective in the treatment of other syndromes, such as bulimia nervosa, panic fits and obsessive–compulsive disorder. An instrumental setup including off-line solid phase micro-extraction coupled to spectrophotometry has been constructed to improve the sensitivity for quantification of fluoxetine in real samples. The method was applied to analysis of spiked wastewater samples with the recovery 89.9%. This research provides an overview of the new developments in material and format technology that improve the extraction of semi-polar compounds in several extraction techniques. It mainly include a solid-phase µ-extraction, uses a simple silver nanoparticles. The influences of micro-extraction conditions such as pH, salt effect, performance and desorption conditions were investigated. The method has a high enrichment factor and excellent selective clean-up of sample. Reasonable relative recovery were also obtained. The linear calibration curves was obtained in the range of 0.1-35 mg.L-1 .We used the method to pre-concentration and clean up fluoxetine from real samples.