Abstract: The waste water-based epidemiology is an important technique to fight against drug abuse by analyzing the concentration of illicit drugs in urban sewage, which can monitor the abuse of drugs.An SPE-UPLC-MS/MS method was developed for the analysis of 12 common drugs and their metabolites involving amphetamine and morphine.It was shown that the best result was achieved when hydrochloric acid/ acetonitrile (5∶95) was added to acidify the sample during the concentration process, guaranteeing the anti-across contamination of the analysis of organic nitrogen basic trace components, and improve the stability, specificity, and accuracy of the method.The optimized method meets the analytical requirements of complex sewage samples, and has been successfully applied to the assessment of urban drug abuse through sewage analysis.