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A simple and specific analytical method was developed and tested for the determination of pharmaceuticals in mollusc samples. A combination of microwave-assisted micellar extraction (MAME) and solid-phase extraction (SPE) using a non-ionic surfactant, polyoxyethylene 10 lauryl ether, was examined to extract and determine simultaneously a group of pharmaceuticals such as carbamazepine, clorfibric acid, ketoprofen, naproxen, bezafibrate and ibuprofen by liquid chromatography using UV-diode array detector. The MAME extraction performance was evaluated by studying various parameters such as the volume and concentration of surfactant and microwave conditions. Finally, an OASIS HLB cartridge was used as an optimum SPE sorbent to clean up the extracts and preconcentrate the selected analytes. The proposed method showed satisfactory linearity and reproducibility (between 3 and 15%), as well as detection limits ranging from 30 to 220 ng/g. Finally, the method was successfully applied to the determination of the target pharmaceuticals in various kinds of mollusc samples. This study has demonstrated that microwave-assisted micellar extraction with solid-phase extraction may be used as a viable alternative to conventional methods for the extraction of pharmaceuticals in this type of matrices.