Quantitation of pilsicainide in microscale samples of human biological fluids using liquid chromatography-tandem mass spectrometry

摘要

This paper describes a sensitive, reliable method to determine pilsicainide (PLC) levels in microscale sample volumes of human biological fluids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). PLC and quinidine as an internal standard were extracted with diethylether from 0.1 mL of alkalinized biological fluids. The extract was injected into an analytical column (L-column 2 ODS, 75 mm x 2.1 mm i.d.). The mobile phase for separation consisted of 5 mM ammonium acetate (pH 4.5)/methanol (4:1, v/v) and was delivered at a flow rate of 0.2 mL/min. The drift voltage was 100V. The sampling aperture was heated at 120 degrees C and the shield temperature was 260 degrees C. The ion transitions used to monitor analytes were m/z 273 -> m/z 110 for PLC and m/z 325 -> m/z 79 for quinidine. The total time for chromatographic separation was less than 8 min. The validated concentration ranges of this method for PLC were 5-2000 ng/mL in plasma, 5-500 ng/mL in ultrafiltered plasma solution, and 25-2000 ng/mL in urine. Mean recoveries of PLC in plasma, ultrafiltered plasma solution, and urine were 93.2-99.7%, 91.4-100.6%, and 93.9-104.7%, respectively. Intra- and interday coefficients of variation for PLC were less than 6.0% and 4.3% in plasma, 6.1% and 3.7% in ultrafiltered plasma solution, and 5.4% and 2.5% in urine at the above concentration ranges, respectively. The lower limit of quantification for PLC in plasma, ultrafiltered plasma solution, and urine were 5 ng/mL, 5 ng/mL, and 25 ng/mL, respectively. This method can be applied to pharmacokinetic study and therapeutic drug monitoring in special populations such as neonates, infants, and the elderly by making effective use of residual samples used for general clinical laboratory testing. (C) 2015 Elsevier B.V. All rights reserved.