A panel of 22 synthetic cannabinoid drugs and metabolites were extracted from urine and analyzed by UPLC-MS/MS. The use of Oasis HLB μElution plates enabled the simultaneous extraction of acidic, basic and neutral compounds, ensuring that a wide variety of compounds and metabolites could be analyzed. Separation using the CORTECS UPLC C18 Column enabled the analysis of all compounds in a short analysis time with baseline resolution of critical isobaric pairs. Separation efficiency and peak widths were superior to fully porous columns of matching dimensions and particle size. This method enables the rapid and reliable extraction and analysis of this critical class of compounds for forensic toxicology. The excellent performance seen on this variety of compounds and the universal nature of the extraction method should allow its use on other synthetic cannabinoids and metabolites, an important feature given the rapid development of new, related compounds.