液相-串联质谱法测定人血浆中左舒必利浓度

Determination of levosulpiride in human plasma by LC-MS/MS

目的：建立测定人血浆中左舒必利浓度的方法。方法：血浆样品经乙腈沉淀蛋白后,采用液相-串联质谱（LC-MS/MS）法测定血浆样品中左舒必利浓度,以吡格列酮为内标,以正离子多反应监测（MRM）扫描方式进行检测。用于定量的离子为m/z342.1→112.1（左舒必利）和m/z357.1→134.0（吡格列酮）。色谱柱为Capcell Pak CR（2.0mm×150 mm,5μm）,流动相为乙腈-20 mmol·L-1醋酸铵（含0.3%甲酸）（65∶35）。结果：血浆中左舒必利的线性范围为3～4 000 ng·ml-1,定量限为3 ng·ml-1,批内RSD≤4.94%,批间RSD≤5.93%,准确度（RE）在-6.48%～3.42%之内,平均相对回收率在93.52%～103.42%之间。结论：该方法专属性强、灵敏度高、重复性好,符合血浆样品测定的要求,适用于人体血浆中左舒必利浓度的测定和药动学考察。

OBJECTIVE To develop a method for the determination of levosulpiride in human plasma.METHODS Plasma samples were precipitated by acetonitrile and LC-MS/MS method was adopted to determine levosulpiride in human plasma using pioglitazone as the internal standard.The detection was performed by multiple reaction monitoring（MRM）mode via a positive electrospray ionization source.The monitoring transition ion-pair was m/z 342.1→112.1 for levosulpiride and m/z 357.1→134.0for pioglitazone.The separation was performed on a Capcell Pak CR column（2.0mm×150 mm,5μm）with a mobile phase consisted of acetonitrile and 20 mmol·L-1 ammonium acetate（0.3%formic acid）（65∶35）.RESULTS The calibration curves of levosulpiride in human plasma were linear over the concentration range 3-4 000 ng·ml-1 with a lower limit of quantitation of 3.0ng·ml-1.The RSDs（%）of intra-day and inter-day precision were less than 4.94% and 5.93%,respectively.The accuracies were between-6.48% and 3.42% and the mean relative recovery of levosulpiride ranged from93.52% to103.42%.CONCLUSION The method is very selective and highly sensitive with good reproducibility,which meets the requirement of determination of plasma samples and can be applied for the determination of levosulpiride in human plasma and the study on pharmacokinetics.