LC-MS/MS法测定氟哌啶醇在大鼠体内的血药浓度及其药动学研究  

Study on Plasma Concentration and Pharmacokinetics of Haloperidol in Rats by LC-MS/MS

作　　者：雷凯[1] 贺国芳[1] 何光照[2] 张思[1] 刘雅楠[1] 刘东[1] 任秀华[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,武汉430030 [2]常州市肿瘤医院

出　　处：《中国药师》2017年第1期82-86,共5页China Pharmacist

基　　金：湖北省自然科学基金项目(编号:2016CFB628)

摘　　要：目的:建立液相色谱-串联质谱法测定大鼠血浆中氟哌啶醇浓度,并探索氟哌啶醇在大鼠体内的药动学特征。方法:以咪达唑仑为内标,血浆样品经乙腈沉淀蛋白提取分离。前置柱:菲罗门C_(18)柱;色谱柱:Symmetry~ C18柱(50 mm×2.1 mm,3.5μm);流动相:10 mmol·L^(-1)乙酸铵(用甲酸调节p H至3.4)-乙腈;流速:0.3 ml·min^(-1),采用梯度洗脱;柱温:40℃;进样量为10μl。离子源:ESI源;检测方式:正离子模式;扫描方式:多反应离子监测(MRM);喷雾电压:5 500 V;温度:450℃;GAS1和GAS2流速:50 ml·min^(-1);用于定量分析的离子反应分别为氟哌啶醇(m/z 376.2→165.1,碰撞能为32 e V)和咪达唑仑(m/z 326.1→291.2,碰撞能为35 e V)。结果:氟哌啶醇在1.0~200.0 ng·ml^(-1)浓度范围内线性关系良好(R^2=0.997 7),提取回收率在75.2%~86.3%。主要药动学参数AUC_(0-t)为(175.5±21.3)ng·h·ml^(-1),t_(1/2)为(2.12±0.24)h,C_(max)为(97.7±21.6)ng·ml^(-1)。结论:该方法操作简便、快速、准确、重复性好,可应用于氟哌啶醇在大鼠体内的药动学研究。Objective ： To establish a method for the determination of haloperidol in rat plasma by LC-MS/MS and study its phar- macokinetics. Methods： With midazolam as the internal standard, the plasma samples were extracted by acetonitrile. Pre-column was a Phenomenex C18 column and the column was a Symmetry C18 column. The mobile phase was ammonium acetate （ pH was adjusted to 3.4 by formic acid） -acetonitrile and the flow rate was 0.3 ml min-1. The column temperature was 40 ℃ and the injection volume was 10 μl. The ion source was ESI and the detection mode was positive ion mode. The scan mode was multiple reactions monitoring （MRM） and the spray voltage was 5 500 V. The temperature was 450℃. The GAS1 and GAS2 flow rate was 50 ml min-1. The ion reaction used for quantitative analysis was haloperidol （m/z 376.2→165.1, collision energy of 32 eV） and midazolam （m/z 326.1→ 291.2, collision energy of 35 eV）. Results： Haloperidol had a good linear relationship within the range of 1.0-200.0 ng ml -1 and the extraction recovery was 75.2% -86.3%. The main pharmacokinetic parameters were as follows ：AUC0-t of （ 175.5 ± 21.3 ） ng h ml-1, t1/2 of （2.12±0.24）h, and Cmax of （97.7 ± 21.6）ng ml-1. Conclusion： The method is simple, rapid and accurate with good repeatability, which can be used for the plasma concentration monitoring and pharmacokinetic study of haloperidol.

关 键 词：氟哌啶醇 液相色谱-串联质谱法 药动学 大鼠 

分 类 号：R969.1[医药卫生—药理学]