HPLC-MS/MS法测定人体血浆中丙泊酚的浓度及其药动学研究(英文)

HPLC-MS/MS determination and pharmacokinetic study of propofol in human plasma

目的:采用HPLC-MS/MS法检测人体血浆中丙泊酚的浓度,并将该方法用于临床药动学研究。方法:采用Zorb-ax Eclipse XDB-C18(50 mm×4.6 mm,5μm)色谱柱分离;流动相为甲醇和0.1%氨水二元梯度洗脱系统;流速为0.3 mL.min-1;通过电喷雾离子化电离源(ESI),采用负离子检测。结果:线性范围为0.010～12μg.mL-1,相关系数≥0.99,定量下限为0.010μg.mL-1。日内及日间精密度不高于15%,准确度的相对误差(RE)在-2.0%～5.0%。药代动力学符合三室模型,清除率为0.029 L.min-1.kg-1,中央室分布容积为0.60 L.kg-1,血药浓度消除半衰期t1/2α为0.84 min,t1/2β为6.7 min,t1/2γ为128.7 min。结论:该方法高效、灵敏,特异性强,准确度、精密度好,适用于丙泊酚药物动力学研究。

Objective ：To develop a rapid, simple and sensitive high performance liquid chromatography -tandem mass spectrometry（ HPLC -MS/MS）method for the quantitative determination and pharmacokinetic study of propo- fol in human plasma. Methods：Separation was performed on a Zorbax Eclipse XDB - C18 column column（50 mm × 4.6 mm,5 μm） with gradient elution at a flow rate of 0. 3 mL. min^-1. The mobile phase was 0. 1% aqueous ammo- nium hydroxide and methanol. Detection was performed in a triple - quadruple tandem mass spectrometer by multi- ple -reaction -monitoring mode via electrospray ionization. Results： Linear calibration curve was obtained in the concentration range of 0. 010 - 12μg. mL^-1 （r≥0.99） ,with a lower limit of quantification of 0. 010 μg. mL-1- The intra-and inter- day precision（RSD） values were below 15% and accuracy（RE） ranged from- 2.0% to 5.0% at all QC levels. A three - compartment pharmacokinetic model best described the pbarmacokinefics of propo- fol. Clearance was 0. 029 L . min^-1 . kg^-1, the volume of distribution of the central compartment was 0. 60 L .kg^-1, elimination half- life t1/2α was 0.84 min, t1/2α was 6.7 min and t1/2α was 128.7 min. Conclusion： A rapid, accurate and sensitive method was developed and successfully applied to the pharmacokinetie study of propofol in healthy Chinese volunteers following intravenous administration.