Development and validation of a rapid and sensitive UHPLCeMS/MS method for the determination of paliperidone in beagle dog plasma

摘要

In order to evaluate the pharmacokinetic profile of paliperidone extended-release tablets in vivo,a simple and rapid ultra-high performance liquid chromatographyetandem mass spectrometry(UHPLCeMS/MS)method was developed and validated for the determination of paliperidone in beagle dog plasma.Paliperidone and diazepam(internal standard)were extracted from plasma samples with diethyl ether,and then separated on a C_(18) column(2.1×50 mm,2.6 mm)under gradient elution with methanol-0.1%formic acid at a flow rate of 0.3 ml/min.The compounds were detected using a triple-quadrupole mass spectrometer equipped with an electrospray ionization(ESI)source.The validated method was linear over the concentration range of 1.00-1000.00 ng/ml and the lower limit of quantitation was 1.00 ng/ml.The intra-day and inter-day precision values were not more than 15%(relative standard deviation<20%at low levels),while the accuracy was within±10%of nominal values.The validated UHPLC-MS/MS method was successfully applied to an oral pharmacokinetic study of paliperidone extended-release tablets in a beagle dog.