Many publications have shown that PPCPs are present at parts-per-trillion (PPT) levels in rivers and streams. Methods therefore need to be able to detect compounds at these trace levels. In addition to the low level detection of PCPPs, a major analytical challenge for analysis lies in the wide chemical diversity of compound classes and structures. Furthermore, the complexity of the water samples requiring analysis can be very diverse. This application note demonstrates the extraction, separation, and detection of 78 PPCPs including acidic, basic, and neutral compounds in well and surface water samples. Using the ACQUITY UPLC H-Class System with the small, benchtop Xevo TQD, it was possible to analyze all compounds in a single injection.