This experiment combines analytical techniques of solid-phase extraction (SPE) and gas chromatography quadrupole time-of-flight mass spectrometry (GC-QTOF-MS) to determine organochlorine pesticides (OCPs) in river water as a means to develop and improve student understanding of the use of GC-QTOF-MS for qualitative and quantitative analysis. In the classroom, students are presented with the principles and instrumentation of SPE, GC, and QTOF-MS via conventional lectures and question--answer sessions. In the laboratory, they are introduced to the procedure for tuning GC-QTOF-MS and developing a new method, analyzing OCPs in standard solutions to obtain retention times and characteristic ions, employing the mass spectrometry data to conduct library matching, and completing the identification and quantification of OCPs in the river. Additionally, students learn how to deduce the chemical formula of an "unknown" eluent compound by relying on high-resolution mass measurements and isotopic distributions. This method could be applied in the courses of instrumental analysis or environmental analysis. It could be readily adapted to other analytes such as the presence of steroids or other pharmaceuticals.