The concentration determination of toxic substances and their metabolites in sewage is the key to evaluate drug use by sewage analysis. The basic idea of the method is to detect drugs and metabolites in sewage, but drug metabolites are mixed with domestic sewage after entering the sewage system. The content of compounds can be diluted thousands of times, and the concentration is generally at the level of ng / L. At the same time, the complex matrix in sewage also puts forward higher requirements for the antipollution ability of the instrument. Compared with the traditional off-line solid phase extraction, on-line SPE has the advantages of high sample utilization and less samples; Full volume automatic on-line extraction, desorption and sample injection, high flux, which can greatly save manpower and time cost; At the same time, the cross pollution of pretreatment is relatively less. Therefore, it is very popular with front-line testers in the actual sewage drug testing work. Based on this, we developed SCIEX on-line SPE-MS / MS system for qualitative and quantitative analysis of 12 drugs and metabolites in sewage.