HPLC-MS/MS法测定人血浆中赖诺普利的浓度

HPLC-MS/MS determination of lisinopril in human plasma

目的:建立测定人血浆中赖诺普利浓度的 HPLC-MS/MS 法。方法:200μL待测血浆中定量加入内标后,直接加入蛋白沉淀剂三氟醋酸,涡旋离心后取上清液直接进样。采用 Zorbax Eclipse DB-C_8柱(5μm,150 mm×4.6 mm)分析柱;流动相为甲醇-12.5 mmol·L^(-1)醋酸铵缓冲液(60:40,pH=4.40),流速0.5 mL·min^(-1);进样量25μL。质谱检测采用 ESI 正离子模式,扫描方式为多反应监测方式,扫描离子对为 m/z406.3→84.0(赖诺普利)和 m/z 349.1→206.1(内标依那普利拉)。结果:本文所建立测定赖诺普利的线性范围为1.064～851.2 ng·mL^(-1),最低定量限可达1.064 ng·mL^(-1)。测定的方法回收率为97.52%～103.2%;日内 RSD<7%,日间 RSD<5%。结论:本文所建立的方法灵敏度良好、准确度高,可用于赖诺普利的药代动力学研究及临床药物浓度监测。

Objective：To establish an HPLC - MS/MS method for determination of lisinopril in human plasma. Methods ：The plasma samples were treated by trifluoroacetic acid before analysis. 25 μL supernatant was performed on a Zorbax Eclipse DB - C8 analytical column（5 μm,150 mm ×4.6 mm） using methanol - 12. 5 mmol · L^-1 （pH =4. 40） ammonium acetate buffer solution （60： 40） as the mobile phase. The flow rate was 0. 5 mL · min^-1. The mass spectrometer was operated under the positive ion mode and multiple reaction monitoring with the transitions of m/z 406. 3→84. 0 and m/z 349. 1→206. 1 was used to qualify lisinopril and enalapril,respectively. Results：The linear calibration curve was obtained in the 1. 064 - 851.2 ng · mL ^- 1, the lower limit of quantification was 1. 064 ng · mL ^- 1. The method recovery was 97.52% - 103.2%. Intra - day and inter - day relative standard deviations of assay were less than 7% and 5% ,respectively. Conclusion：The proposed method is simple ,rapid and sensitive and can be used for pharmacokinetical study and clinical drug monitoring.