Teaching Undergraduates LC–MS/MS Theory and Operation via Multiple Reaction Monitoring (MRM) Method Development

This laboratory experiment employs an innovative approach to introduce undergraduates to liquid chromatography–tandem mass spectrometry (LC–MS/MS) by developing a method based on multiple reaction monitoring (MRM). During this qualitative investigation, students operated a triple quadrupole mass spectrometer in the MS scan and product ion scan modes to determine precursor and product ions, respectively, for a vanillin, ethyl vanillin, and coumarin standard mixture. After identifying precursor → product ion transitions, students conducted a 2 min liquid chromatography run in MRM mode. Students were astonished by the speed, selectivity, and sensitivity of the LC–MS/MS method compared to that of a liquid chromatograph with ultraviolet detection.