A fast and sensitive monitoring method for trace pharmaceuticals in the environment is vital because many of these compounds are ubiquitous, persistent, and biologically active with recognized endocrine-disruption and pharmacological functions. A rapid and reliable ultra high-performance liquid chromatography combined with tandem mass spectrometry was developed in the present study to simultaneously identify, confirm, and quantify 60 target pharmaceuticals in wastewater samples. The method uses a sub-2 µm particle column for separating target compounds, which were subsequently quantified with the mass spectrometer. Using this high-throughput analysis method, a single injection could provide results within 5 min for the pharmaceuticals. All of the target compounds were analyzed by the multiple-reaction monitoring with 15-ms fast polarity switching. Both intraday and interday precision analyses indicate excellent coefficient of variability. To evaluate the performance of the method, a standard solution (100 and 1000 ng L(-1)) was spiked into complex wastewater samples. The tailing factor and peak width were also monitored and adjusted for optimizing peaks from the ultra high-performance liquid chromatograph. Of the target pharmaceuticals in wastewater of a sewage-treatment plant analyzed on an hourly basis, only 17 compounds were detected, and others were lower than the method detection limits. Acetaminophen, cimetidine, and iopromide were all detected at >1 μg L(-1), and their concentration profiles were similar to that of a nonsteroidal anti-inflammatory drug detected in wastewater. Other noticeable pharmaceuticals were sulfamethoxazole and trimethoprim. Sources of pharmaceuticals in wastewater are briefly discussed.