This Application Note describes a simple, sensitive quantification method for lovastatin in human plasma, based on a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC/ESI/MS/MS) technique. Solid phase extraction was used for the extraction of lovastatin from plasma, and simvastatin was used as the internal standard. For quantification, the triple-quadrupole MS was used in multiple reaction monitoring (MRM) mode. The monitored transitions were m/z 405.4 to 199.2 for lovastatin and m/z 419.1 to 199.2 for simvastatin. A linearity coefficient of R2 > 0.99 was observed over a wide range of 0.1 ppb to 50 ppb of lovastatin in human plasma. Several methods are currently available for the quantification of this statin, but sensitivity and shorter runtime were the major challenges in those methods. The advantages of the method described here are simplicity, short runtime (1.2 minutes) and better sensitivity through MRM.