Objective To establish a method for the detection of 12 synthetic pigments in wine by solid-phase extraction/ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).Methods After the wine is subjected to purification and enrichment via solid-phase extraction, 12 synthetic pigments are determined using ultra-high performance liquid chromatography for separation and mass spectrometry in multiple reaction monitoring (MRM) mode. The influence of matrix effect on the determination is corrected using a matrix-matched calibration curve.Results For the 12 synthetic pigments within the range of 0.2~20 000 μg/L, the peak area has a good linear relationship with their mass concentration, and the coefficient of determination R²≥0.982 0. The recovery rates for the analytes at different spiked levels range from 90.8% to 105.1%, with relative standard deviations (RSDs) of 2.1%~4.9%. The limits of detection (LODs) of the method are 0.006~1.500 μg/kg, and the limits of quantitation (LOQs) are 0.02~5.00 μg/kg. The method is used to detect 10 batches of wine samples of different types, of which 5 samples are found to contain acid yellow 36 and indigo carmine.Conclusion It is simple, highly sensitive, and offers a wide linear range, making it suitable for the routine determination of the 12 synthetic pigments in wine.