Measurement of metanephrines and normetanephrine in plasma is challenging due to the low physiological concentrations, their hydrophilic nature1, and time consuming traditional sample preparation. With use of the PerkinElmer QSight® 220 triple quadrupole mass spectrometer, LC-MS/MS analysis was performed using the recently advanced solid phase extraction (SPE) sorbent technology (“load, wash, elute”) method protocol. As a result low levels of ME and NOR are detectable in plasma with short sample preparation and LC run time. This LC-MS/MS method provides a fast, sensitive, accurate, and reproducible solution for the analysis of ME and NOR in plasma.