not-yet-known not-yet-known not-yet-known unknown An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of three ephedrine psychoactive substances in water. By optimizing chromatography conditions, mass spectrometry parameters, and solid-phase extraction (SPE) conditions (including the SPE column, sample pH, washing, and elution), the optimal treatment conditions were determined. Poly-Sery MCX was selected as the extraction column, with samples loaded at pH 3. A 4 mL solution of 2% formic acid in water was used as the eluent, and a 5 mL solution of 5% ammonia in acetonitrile was used to elute the target compounds. The best results were obtained when the residue was redissolved in acetonitrile after nitrogen evaporation. The method exhibited a good linear relationship in the range of 0-50.00 μg/L, with determination coefficients (R 2) greater than 0.9990. The detection limit and quantitation limit were 0.05-0.10 μg/L and 0.20-0.50 μg/L, respectively. Recovery rates of the target compounds in blank sewage at three different concentration levels ranged from 92.37% to 106.31%, with relative standard deviations (RSD) of 0.77-4.83% (n=7). This method has been successfully applied to the analysis of surface water and domestic sewage, demonstrating stable treatment effects and practical significance for detecting ephedrine psychoactive substances in water.