This thesis has been performed at Clinical Chemistry at Sahlgrenska University Hospital in Gothenburg. The purpose of the project was to investigate new and alternative ways to determinate synthetic cannabinoids by gas chromatography-mass spectrometry. Currently, the possibilities to quantify synthetic cannabinoids are very limited. This can lead to an increased use of synthetic cannabinoids as the risk of detection is low, which may be known by drug users. The synthetic cannabinoids are sold mixed with different herbs and have varying names like Spice Gold, Spice Silver, K2, Smoke and Pot-pourri. The synthetic cannabinoids analyzed were JWH-018 and JWH-073, which are commonly found in seized Spice material. At intake of these drugs, usually through smoking, cannabis-like effects arise. This is because they bind to cannabinoid receptors in a similar way as THC does, which is the primary active cannabinoid of cannabis. For urine samples an analytical method would probably be the most sensitive if the major metabolite could be analyzed, as it is expected to be present in high concentrations in this sample type. Since information regarding the metabolism of synthetic cannabinoids is very limited there may be reasons to analyze the mother substance in urine. Further, in plasma and serum samples the mother substance is expected in high concentrations. Thus different ways to detect JWH-018 and JWH-073 directly were investigated in this project. Derivatization of JWH-018 and JWH-073 was the first step to get more selective and sensitive GC-MS analysis. Different derivatization-reagents were investigated, for example BSTFA and TFAA. The results show that the derivatization of JWH-018 with BSTFA after reduction and extraction was successful. To achieve this, samples had to be heated at 115°C for 1-3 hours, but still the samples were not completely derivatized. The results indicate that JWH-substances are difficult to derivatized, but they are possible to derivatize with BSTFA. This could mean that a GC-MS-method maybe could be established for these substances, preferably trough TFAA-derivatization.