A new, rapid, and automated method for the quantitation of 21 synthetic cathinones in urine was established using magnetic dispersive solid-phase extraction (MDSPE) in combination with direct analysis in real time-high-resolution mass spectrometry (DART−HRMS). Sample preparation and quantitation were verified by liquid chromatography−tandem mass spectrometry (LC-MS/MS). Methcathinone-D3, α-PVP-D8, and proadifen (SKF525A) were used as internal standards. Magnetic HLB extractant and NaH 2 PO 4 /NaOH buffer (0.2 M, pH 7) were used in automatic MDSPE. All 21 synthetic cathinones could be detected and analyzed by DART−HRMS in under 1 min. It was proven that the linearities of 21 synthetic cathinones were suitable (R 2 > 0.99) in the concentration ranges of 0.5−100 ng/mL or 1−100 ng/mL. The precision and accuracy values were all within ±15%, and the samples were stable under various conditions. The average time of each sample from preprocessing to completion of detection was approximately 2 min, allowing for rapid sample analysis. The relative error (RE) of the concentrations obtained by DART−HRMS and LC−MS/MS were within ±13.61%, and the linear coefficient (R) was 0.9964. The results of DART−HRMS and LC−MS/MS provided equivalent values at the 95% confidence level. In summary, a simple, fast, and convenient quantitation method via DART−HRMS was established. This application can be utilized to reduce backlogs and promote rapid case processing.