Determination of lovastatin in human plasma by ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry and its application in a pharmacokinetic study

A selective, rapid and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed for the quantitative determination of lovastatin in human plasma and its application in a pharmacokinetic study. With mycophenolate mofetil as internal standard, sample pretreatment involved a one-step extraction with tert-butyl methyl ether of 0.2 ml plasma. The analysis was carried out on an ACQUITY UPLCTM BEH C18 column (50 mm × 2.1 mm, i.d., 1.7 μm) with flow rate of 0.35 ml/min. The mobile phase was 20% water and 80% acetonitrile (v/v). The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI). Linear calibration curves were obtained in the concentration range of 0.08–24.50 ng/ml, with a lower limit of quantification of 0.08 ng/ml. The intra- and inter-day precision (RSD) values were below 15% and accuracy (RE) was −7.6 to 9.3% at all QC levels. The method was applicable to clinical pharmacokinetic study of lovastatin in healthy volunteers following oral administration.