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Copper oxide nanoparticles loaded on activated carbon (CuO-NPs-AC) were prepared and fully analyzed and characterized with FE-SEM, XRD and FT-IR. Subsequently, this novel material was used for simultaneous ultrasound-assisted adsorption of brilliant green (BG), auramine O (AO), methylene blue (MB) and eosin yellow (EY) dyes. Problems regard to dyes spectra overlap in quaternary solution of this dyes were omitted by derivative spectrophotometric method. The best pH in quaternary system was studied by using one at a time method to achieved maximum dyes removal percentage. Subsequently, sonication time, adsorbent dosage and initial dyes concentrations influence on dyes removal was optimized by central composite design (CCD) combined with desirability function approach (DFA). Desirability score of 0.978 show optimum conditions set at sonication time (4.2 min), adsorbent mass (0.029 g …