lacidipine and methyl-tert-butyl-ether

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 C18 column (50 mm x 2.1 mm, 1.7 microm) 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.

Topics: Acetates; Administration, Oral; Buffers; Calcium Channel Blockers; Calibration; Chromatography, Liquid; Clinical Trials as Topic; Dihydropyridines; Drug Stability; Freezing; Humans; Hydrogen-Ion Concentration; Male; Methyl Ethers; Molecular Structure; Nifedipine; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tablets; Tandem Mass Spectrometry