RationaleIn　recent　years,　ephedrine　psychoactive　substances　have　attracted　much　attention　due　to　their　prevalence　in　water　bodies　and　potential　threat　to　aquatic　ecosystems.　Psychoactive　substances　have　been　considered　as　a　new　type　of　environmental　pollutant　due　to　their　unpredictable　potential　risks　to　the　behavior　and　nervous　system　of　non-target　organisms.　A　rapid,　sensitive,　selective,　and　robust　method　for　the　quantification　of　three　ephedrine　psychoactive　substances　in　sewage　is　needed.MethodsAn　ultraperformance　liquid　chromatography-tandem　mass　spectrometry　(UPLC-MS/MS)　method　was　developed　for　the　simultaneous　determination　of　three　ephedrine　psychoactive　substances　in　water.　The　optimal　processing　conditions　were　determined　by　optimizing　the　chromatography-mass　spectrometry　and　solid-phase　extraction　(SPE)　conditions　(e.g.,　the　SPE　column,　sample　pH,　washing,　and　elution),　and　the　treatment　conditions　were　determined;　this　was　achieved　via　positive　ion　scanning　in　multiple　reaction　monitoring　mode.　Poly-Sery　MCX　was　selected　as　the　extraction　column,　with　samples　loaded　at　pH　3.　And　4-mL　solution　of　2%　formic　acid　(FA)　aqueous　solution　was　used　as　the　eluent;　the　target　compounds　were　eluted　with　5　mL　of　5%　NH4OH　in　acetonitrile　(ACN)　solution.　The　best　results　were　obtained　when　the　residue　was　resolubulization　in　ACN　after　nitrogen　evaporation.ResultsThe　developed　UPLC-MS/MS　showed　a　good　linear　relationship　in　the　range　of　0-50.00　mu　g/L,　with　determination　coefficients　(R2)　greater　than　0.9990.　The　detection　limit　and　quantitation　limit　were　0.05-0.10　and　0.20-0.50　mu　g/L,　respectively.　Recovery　rates　of　the　target　compounds　in　blank　sewage　at　three　different　concentrations　ranged　from　92.37%　to　106.31%,　with　relative　standard　deviations　(RSDs)　of　0.77%-4.83%　(n　=　7).ConclusionsThis　method　has　been　successfully　applied　to　the　analysis　of　surface　water　and　domestic　sewage,　and　the　samples　were　processed　stably,　indicating　that　the　method　is　practical　for　the　determination　of　ephedrine　psychoactive　drugs　in　water　bodies.