Background & Objectives: Biosorbents do not show desirable performance under undesirable conditions. MOLECULARly IMPRINTED POLYMERS (MIPs) have thus been proposed to resolve this issue. In an attempt for specific absorption of trace triazine herbicides, an MIP was synthesized, optimized, and used as a novel tool for MOLECULARly IMPRINTED solid phase extraction (MISPE).Methods: Atrazine and ametryn POLYMERS were synthesized using the central composite design. These POLYMERS, along with control samples, were evaluated in terms of the amount of functional monomer, template molecule, cross-linker, initiator, solvent, and polymerization temperature. The appropriate cartridge was then selected and the response surface method was applied to optimize the MISPE based on the amount of absorbent and the volume, concentration, flow rate, and pH of the sample. Finally, the concentration factor and reusability of the cartridge were examined.Results: The optimized temperature for ametryn and atrazine was calculated as 40.86oC. The solvent, cross-linker, initiator, monomer, and template molecule were 6.41 and 5.03 ml, 27.070 and 21.320, 2.03 and 2.27 mmol, 5.41 and 4.73 mmol, and 1.204 and 0.811 mmol, respectively. The results of MISPE optimization of ametryn and atrazine suggested a recovery rate of over 90% for drinking water and urine.Conclusion: The results showed that the central composite design can be used as a general tool for polymer synthesis and optimization and MISPE protocol. Furthermore, due to their high performance and selectivity, POLYMERS can assume an important role in workplace monitoring.