Hydrophilic interaction liquid chromatography–tandem mass spectrometry for the determination of levosulpiride in human plasma

A rapid, sensitive and selective hydrophilic interaction liquid chromatography–tandem mass spectrometric (HILIC–MS/MS) method for the determination of levosulpiride in human plasma was developed. Levosulpiride and internal standard, tiapride were extracted from human plasma with ethyl acetate at pH 11 and analyzed on an Atlantis HILIC silica column with the mobile phase of acetonitrile–ammonium formate (190 mM, pH 3.0) (94:6, v/v). The analytes were detected using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.999) over the concentration range of 1.00–200 ng/ml. The lower limit of quantification for levosulpiride was 1.00 ng/ml using 100 μl plasma sample. The coefficient of variation and relative error for intra- and inter-assay at three quality control (QC) levels were 3.8–9.1 and −2.9 to −0.1%, respectively. The recoveries of levosulpiride ranged from 80.5 to 87.4%, with that of tiapride (internal standard) being 84.6%. This method was successfully applied to the pharmacokinetic study of levosulpiride in humans.