Ultra-performance liquid chromatography–tandem mass spectrometry for the determination of lacidipine in human plasma and its application in a pharmacokinetic study

Abstract

A selective, rapid and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–ESI-MS/MS) method was developed and validated for the quantification of lacidipine in human plasma. With nifedipine as an internal standard, sample pretreatment involved a simple liquid–liquid extraction with tert-butyl methyl ether of 1 ml plasma. The analysis was carried out on an Acquity™ UPLC BEH C 18 column (50 mm × 2.1 mm, 1.7 μm) with flow rate of 0.28 ml/min. The mobile phase was 30 mM ammonium acetate buffer–acetonitrile (18:82, v/v, pH 5.5). 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 0.025–10.000 ng/ml, with a lower limit of quantification of 0.025 ng/ml. The intra- and inter-day precision (R.S.D.) values were below 15% and accuracy (RE) was −12.7% to 11.9% at all QC levels. The method was successfully applied to a clinical pharmacokinetic study of lacidipine in healthy volunteers following oral administration.