A large number of synthetic cannabinoids are included in new psychoactive substances (NPS) and constitute an open research area in analytical pharmaceutical and toxicology, when methods are needed to unambiguously identify these substances and their metabolites in biological fluids. A full molecular characterization of five synthetic cannabinoid molecules of the URB series was achieved by high resolution mass spectrometry (HRMS) in positive ion electrospray ionization and collisional experiments on the protonated parent ions obtaining characteristic fragmentation patterns. Ultra–high performance liquid chromatography (UHPLC–MS/MS) has also been used, which can help develop methods for screening and confirming synthetic cannabinoids in biological fluids.