Drug analysis is an indispensable task in controlling drug abuse, which is a serious problem worldwide nowadays. In this study, we report a simple and rapid approach for detection and quantitation of drugs-of-abuse in urine and oral fluid by wooden-tip electrospray ionization mass spectrometry (WT-ESI-MS). We demonstrated that ketamine, one of the most common abused drugs, and its major metabolite, norketamine, in raw urine and oral fluid could be readily detected and quantified by WT-ESI-MS with only little sample preparation and no chromatographic separation, and the analytical performances, including the linear range, accuracy, precision, LOD and LOQ, were well acceptable for analysis of real samples.