摘要
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 to detect the concentration of hydroxychloroquine（HCQ） in human plasma by HPLC-MS/MS. METHODS Chromatograph was carried out on a Kinetex C18 column. The mobile phase was 0. 6G formic acid water （pH 3.2）- methyl alcohol（80.-20）. The flow rate was set at 0.5ml.min-1. Column temperature was 25 ~C. SRM. HCQ ~M ± HI ± m/z 336.2---~247.2~ internal standard CQEM ± HI ± m/z 320. 2---~247.2. Twenty healthy volunteers were given 200 mg of hydroxychloroquine sulfate tablets for each. Hydroxychloroquine concentration in plasma was determined by HPLC-MS/ MS method. RESULTS The retention time of HCQ and internal standard CQ were approximately 1.3 min and 1.5 rain, re- spectively. A good linearity was shown in concentration range 0. 200-100 /lg.L-1 for HCQ. The LLOQ was 0. 2 μg·L-l. The method recovery was 98. 20%-102.75% The inter- or intra- precision was less than 10% in replicate analysis （n = 6）. The pharmacokinetic parameters of hydroxychloroquine were as follows：tmx were （3.85 ± 1.04） h, tl/2 （32. 3 ± 14. 1） h·Cmax （44. 1 ± 27. 6） μg·L-1 ,AUGI72h（617± 88. 9） μg·h·L 1 ,AUG （749± 108） μg·h·L-1 o CONCLUSION The method is proved to be sensitive, robust, convenient, analysis rapid, and suitable for the clinical investigation and monitoring of the drug concentration in the plasma.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2014年第15期1278-1282,共5页
Chinese Journal of Hospital Pharmacy
基金
南京市卫生青年人才项目(编号:QRX11032)
