The first step of the project was to optimize the MRM transitions for each molecule of the chosen list and to define the best mobile phase composition compromise for optimum sensitivity. Once that process done for the 14 selected drugs, several SPE sorbent for extraction of a wide range of different chemical class compounds were tested. The same study was conducted on the choice of the analytical column trying to combine several retention mechanisms. The final stage of development of the method was devoted to optimization of the sensitivity to reach the lowest limit of quantification and to study of the dynamic range for each molecule. Finally the methodology was validated with real wastewater sample to assess extraction and ionization recovery as well as ruggedness of the system.