The invention relates to the technical field of environment detection and is suitable for measuring erythrocin, chloramphenicol, sulfamethoxazole, sulfadiazine, roxithromycin, cefotiam, pyridazol, norfloxacin, ofloxacin, tetracycline and doxycycline in sewage, surface water and bottom mud. After being sampled, a water sample and a mud sample are pretreated and detected through ultra-high performance liquid chromatography-triple quadrupole mass spectrometry, and qualitative diagnosis is conducted through the characteristic ion pair (m/z) of a target compound, a standard curve is drawn accordingto the response value and the corresponding concentration, and the external standard method is used in quantification, so that the contents of various antibiotics in the sample are obtained. The method is accurate, sensitive and simple, and is suitable for measuring the contents of 11 typical antibiotics in the sewage, the surface water and the mud at the same time.