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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 liquid chromatography-tandem mass spectrometry (HPLC-MS / MS) and to investigate the pharmacokinetics of haloperidol in rats. Methods: Midazolam was used as an internal standard, and plasma samples were separated by acetonitrile precipitation. Column: Symmetry ~ C18 column (50 mm × 2.1 mm, 3.5 μm); Mobile phase: 10 mmol·L -1 ammonium acetate (adjusted with formic acid) p H to 3.4) -acetonitrile; flow rate: 0.3 ml · min -1, gradient elution; column temperature: 40 ° C; Ion source: ESI source; Detection method: Positive ion mode; Scanning method: Multiple reaction ion monitoring (MRM); Spray voltage: 5 500 V; Temperature: 450 ℃; GAS1 and GAS2 flow rate: 50 ml · min -1 ; The ionic reactions used for the quantitative analysis were haloperidol (m / z 376.2 → 165.1, collision energy 32 e V) and midazolam (m / z 326.1 → 291.2, collision energy 35 eV). RESULTS: Haloperidol had good linearity (R ~ 2 = 0.997 7) in the concentration range of 1.0 ~ 200.0 ng · ml ~ (-1) and the recoveries ranged from 75.2% to 86.3%. The main pharmacokinetic parameters AUC_ (0-t) were (175.5 ± 21.3) ng · h · ml -1, t 1/2 (2.12 ± 0.24) h and C max were (97.7 ± 21.6) ng · ml ~ (-1). Conclusion: The method is simple, rapid, accurate, reproducible and can be applied to the pharmacokinetics of haloperidol in rats.