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目的:建立人血浆中羟氯喹浓度测定的HPLC-MS/MS法。方法:采用Kinetex C18色谱柱(2.6μm,50 mm×2.1mm);流动相为0.6%甲酸水溶液(pH3.2)-甲醇(80∶20);流速0.5 ml·min-1;柱温为25℃;电喷雾电离(ESI)正离子检测,检测对象:羟氯喹m/z336.2→247.2;内标氯喹m/z320.2→247.2。20名男性健康志愿者单剂量口服硫酸羟氯喹片200 mg(100mg/片),在设计的时间点取静脉血,用建立的方法测定血药浓度。结果:羟氯喹和内标氯喹的保留时间分别在1.3和1.5 min,羟氯喹在0.200~100μg·L-1范围内线性关系良好(r=0.993 0),最低定量浓度为0.2μg·L-1;方法回收率为98.20%~102.75%,批内、批间RSD小于10%(n=6)。主要药动学参数:tmax(3.85±1.04)h,t1/2(32.3±14.1)h,Cmax(44.1±27.6)μg·L-1,AUC0-72 h(617±88.9)μg·h·L-1,AUC0-∞(749±108)μg·h·L-1。结论:该方法灵敏度高、结果准确、样品处理简单、分析快速,适用于羟氯喹制剂的血药浓度测定。
Objective: To establish a method for the determination of hydroxychloroquine in human plasma by HPLC-MS / MS. Methods: Kinetex C18 column (2.6 μm, 50 mm × 2.1 mm) was used. The mobile phase consisted of 0.6% formic acid (pH 3.2) and methanol (80:20) ℃; electrospray ionization (ESI) positive ion detection, test object: hydroxychloroquine m / z336.2 → 247.2; internal standard chloroquine m / z320.2 → 247.2.20 male healthy volunteers single-dose oral hydroxychloroquine sulfate tablets 200 mg (100mg / tablet), venous blood was taken at the designed time point, and the established method was used to determine the plasma concentration. Results: The retention times of hydroxychloroquine and internal standard chloroquine were 1.3 and 1.5 min, respectively. The linearity of hydroxychloroquine was 0.200 ~ 100 μg · L-1 (r = 0.993 0) and the lowest concentration was 0.2 μg · L-1 The recoveries were 98.20% -102.75%. The intra-assay and inter-assay RSD were less than 10% (n = 6). The main pharmacokinetic parameters: tmax (3.85 ± 1.04) h, t1 / 2 (32.3 ± 14.1) h, Cmax (44.1 ± 27.6) μg · L-1 and AUC0-72 h (617 ± 88.9) μg · h · L -1, AUC0-∞ (749 ± 108) μg · h · L-1. Conclusion: The method has high sensitivity, accurate results, simple sample processing and fast analysis. It is suitable for the determination of serum concentrations of hydroxychloroquine preparations.