Abstract: By optimizing sample preservation, pretreatment, and instrument working conditions, the method mentioned by the title was proposed to determine 10 macrolide antibiotics in the environmental water body, including erythromycin dehydrate, roxithromycin, spiramycin, kitasamycin, clarithromycin, oleandomycin, azithromycin, tylosin, tilmicosin, and josamycin. The 1.0 L of water sample was taken, and 50 mL of methanol was added. The sample was passed through a 0.45 μm glass fiber filter membrane, and the filtrate was collected and stored at 4 ℃, with the determination completed within 2 d. An aliquot (500 mL) of the water sample was taken, and its acidity was adjusted to pH 2.0-3.0 using a 50% (volume fraction) hydrochloric acid solution. Then, 25 μL of the mixed surrogated internal standard solution containing 2 mg · L^-1 azithromycin-d₃ and roxithromycin-d₇ and 25 mL of methanol were added, and the solution obtained was mixed well. The 500 mL of the treated water sample was passed through an activated HLB solid phase extraction column at a flow rate of 5-10 mL·min^-1.The column was rinsed with 5 mL of water and purged with nitrogen for 30 min. Subsequently, the column was eluted sequentially with 5 mL of methanol and 5 mL of a methanol solution containing 0.1% (volume fraction) formic acid at a flow rate of 2 mL·min^-1. Then, the eluate was collected, and evaporated to near dryness at 35 ℃ by nitrogen, and then 25.0 μL of the 2 mg·L^-1 clarithromycin-d₃ internal standard solution was added. The solution was diluted to 1.0 mL with a mixed solution of 0.05% (volume fraction, the same below) formic acid solution and acetonitrile at a volume ratio of 80∶20, and the solution obtained was passed through a 0.22 μm organic filter membrane. The filtrate was analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. In the chromatographic analysis, a Eclipse Plus C₁₈ column was used as the stationary phase, and gradient elution was performed using mixed solutions composed of 0.05% formic acid solution and acetonitrile at different volume ratios as the mobile phase. In the mass spectrometry analysis, ionization was carried out in positive ion mode with an electrospray ion source, detection was performed in multiple reaction monitoring (MRM) mode, and quantification was achieved using the internal standard method. It was shown that the linear range for 10 target compounds was 1.0-100 μg · L^-1, with detection limits (3.143s) in the range of 0.4-1.0 ng · L^-1. Test for recovery was conducted using the standard addition method, giving recoveries in the range of 58.4%-100%, and RSDs (n=6) of the determined values ranged from 3.2% to 20%. The proposed method was applied to the analysis of environmental water bodies from different sources, and macrolide antibiotics were detected in all samples, with detection amounts not exceeding 140 ng · L^-1.