液相色谱-串联质谱法测定人血浆中艾普拉唑的浓度

目的: 建立LC-MS/MS法测定人血浆中艾普拉唑的浓度。 方法: 人血浆样本用乙酸乙酯提取后,选用Zorbax SB-C₁₈色谱柱(150 mm×2.1 mm,5 μm),以乙腈-10 mmol·L^-1醋酸铵溶液(80∶20)为流动相,流速为0.20 mL·min^-1;选用三重四极杆串联质谱仪的多重反应监测( MRM)扫描方式进行监测,电喷雾离子化源,正离子方式,选择监测离子反应分别为m/z367.5→m/z184.1(艾普拉唑)和m/z 383.2→m/z 266.8( 内标氯雷他定)。 结果: 艾普拉唑和氯雷他定的保留时间分别为2.0 min和3.9 min;血浆中艾普拉唑的线性范围为5~1500 ng·mL^-1 ( r > 0.99),定量下限为5 ng·mL^-1;日内、日间RSD 均小于15%;低、中、高3个浓度下的提取回收率分别为(76.5±4.9)%、(78.8±6.3)%、(77.1±4.9)%。 结论: 该方法快速、灵敏、准确,专属性强,重复性好,适用于人血浆中艾普拉唑浓度的测定,可应用于艾普拉唑肠溶片的人体药代动力学及生物等效性研究。

Objective: To develop an LC-MS/MS method for concentration determination of ilaprazole in human plasma. Methods: Human plasma samples were first extracted by ethyl acetate,and the analyte as then separated on a Zorbax SB-C₁₈ column (150 mm× 2.1 mm,5 μm)with the mobile phase of acetonitrile and 10 mmol·L^-1 ammonium acetate (80∶20)at a flow rate of 0.20 mL·min^-1.Detection was carried out by electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM)mode of the triple quadrupole rod tandem mass spectrometer.The MRM transitions of m/z 367.5→m/z 184.1 and m/z 383.2→m/z 266.8 were used to quantify ilaprazole and loratadine (the internal standard),respectively. Results: Ilaprazole and the internal standard were eluted at 2.0 min and 3.9 min,respectively. The calibration curve was linear over the concentration range of 5~1500 ng·mL^-1 (r>0.99),with the lower limit of quantitation (LLOQ)of 5 mg·L^-1.Intra-day and inter-day relative standard deviations were both below 15%.The recoveries of low,middle and high concentrations were (76.5±4.9)%,(78.8±6.3)%,and (77.1±4.9)%,respectively. Conclusion: The established method is rapid,sensitive,accurate,specific and reliable,which can be applied in pharmacokinetic and bioequivalent study.