高效液相色谱-质谱-质谱联用法测定人血浆中艾司西酞普兰浓度及其药代动力学研究

目的建立测定人血浆中艾司西酞普兰浓度的高效液相色谱-质谱-质谱联用法.方法血浆样品经甲醇沉淀后进行分析.色谱柱Lichrospher CN柱150 mm×4.6 m I.D.5μm,流动相甲醇水(含15 mmol·L-1乙酸铵)甲酸(72∶28O.1,v/v/v),流速1.0ml·min-1,电喷雾离子化三重四极杆串联质谱检测,以选择离子反应监测(SRM)扫描方式进行检测,采用选择离子反应监测(SRM)方式进行定量分析,用于监测的离子为m/z 325.0→234.0(西酞普兰)和m/z 409.1→238.1(氨氯地平,内标).结果线性范围为0.20～50.00ng·ml-1,最低定量浓度为0.20 ng·ml-1,应用此法测试了10名健康受试者口服草酸艾司西酞普兰片(10 mg)后不同时间的血药浓度,得到艾司西酞普兰药动学参数,Cmax为9.21±2.10 ng·ml-1,Tmax为3.75±1.04h,AUC0-t为514.6±152.3 ng·h·ml-1,AUC0-∞为540.5±162.3 ng·h·ml-1,t1/2为34.06±7.71 h及Ke为0.021±O.004h-1.结论该法专属、灵敏、简便、快速,适用于人血浆中艾司西酞普兰浓度的测定.

A rapid and sensitive method for determination of escitalopram in human plasma and its application in pharmacokinetic study by liquid chromatography-tandem mass spectrometry

AIM: To determine the concentration of escitalopram in human plasma by HPLC-MS/MS and investigate the pharmacokinetics of escitalopram. METH-ODS: The method involved protein precipitation with methanol. The chromatographic separation was achieved within 6.0 min by using methanol-water with 15 mmol·L-1 ammonium acetate-formic acid (72:28:O.1, v/v/v) as mobile phase and a Lichrospher CN 150 mm×4.6 mm analytical column. The analytes were detected using an electrospray ionization tandem mass spectrometry in SRM mode. Detection of the ions was performed by monitoring the transitions of m/z 325.0 to 234.0 for escitalopram and m/z 409.1 to 238.1 for amlodipine (intemal standard), respectively. RESULTS:The standard curve was linear ( r = 0. 999) over the concentration range of 0.20 - 50.00 ng· ml- 1. Accuracy and precision were below the acceptance limits of 15%. The recoveries of escitalopram ranged from 96.0% to 103.6%. The lower limit of quantification for escitalopram was 0.20 ng· ml-1 using 200 μl plasma sample.The pharmacokinetic parameters of escitalopram after a single oral dosing of escitalopram oxalate tablet (10 rog)to ten healthy male volunteers were achieved. The Cmax, Tmax, AUC0-t, AUC0-∞, t1/2 and Ke of escitalopram were 9.21±2.10 ng·ml-1 , 3.75±1.04 h, 514.6±152.3 ng·h·ml-1 ,540.5±162.3 ng·h·ml-1 , 34.06±7.71 h and 0.021±0.004 h-1,respectively. CONCLUSION:The determination of concentration of escitalopram in human plasma by HPLC-MS/MS method was repid, sensitive and reliable. It can be used for clinical pharmacokinetic study of escitalopram.