【摘要】 目的建立测定人血浆中瑞芬太尼的液相色谱-串联质谱检测方法,并研究其在健康人体内的药动学。方法采用液-液萃取法,用萃取液（乙酸乙酯:正己烷=4:1,V/V）提取健康志愿者静脉注射瑞芬太尼不同时间血浆中的瑞芬太尼,选用卡马西平为内标。采用Agilent Zorbax SB-C₁₈（2.1mm×50mm,3.5μm）进行分离,流动相为甲醇-0.1%甲酸水溶液（80:20,V/V）。电喷雾离子源,正离子MRM扫描分析,内标和瑞芬太尼离子对分别是m/z 237→194和m/z 377.5→345、285。结果瑞芬太尼血药浓度在1.0～50.0μg·L^-1范围内线性关系良好（r=0.998 9）,最低检测限为0.5μg·L^-1,相对回收率均在85%～115%范围内,绝对回收率大于75%,日内和日间RSD均小于10%。单剂量注射瑞芬太尼2μg·kg^-1,t_1/2α为（1.659±0.350）min,CL为（0.003±0.001）L·min^-1·kg^-1,AUC_0-∞为（194.779±36.147）mg·L^-1·min^-1。结论本方法操作简便、灵敏度高、精密度好,适用于瑞芬太尼的临床药动学研究。更多还原

【Abstract】 AIM To establish a LC-MS/MS method for determination of plasma remifentanil concentration and to study the correlative pharmacolinetics in healthy volunteers.METHODS The remifentanil in plasma of healthy volunteers in different time points after intravenous injection was extracted with extract liquor （ethyl acetate:hexane=4:1,V/V）and was determined by LC-MS/MS.Taking carbamazepine as internal standard,the separation of remifentanil was separated by Agilent Zorbax SB-C₁₈analytical column（2.1 mm×50 mm,3.5μm）with methanol-0.1%formic acid solution（80:20,V/V）as the mobile phase.ESI and MRM were used with positive ion scans,and the mass transition pairs of m/z 237→194 and m/z 377.5→345, 285 were used to detect internal standard and remifentanil respectively.RESULTS The linear calibration curve of remifentanil showed excellent correlation in the concentration range of 1.0-50.0μg?L^-1with detection limit 0.5μg·L^-1.The relative recoveries were 85%to 115%,the absolute recovery was more than 75%,and intraday RSD and interday RSD were both less than 10%.The main pharmacolinetic parameters of remifentanil were as follows:t_1/2α（1.659±0.350）min,CL（0.003±0.001）L?min^-1?kg^-1,AUC_0-∞（194.779±36.147）mg·L^-1·min^-1。CONCLUSION The established method is shown to be simple,sensitive and accurate,which can be used for the clinical study of remifentanil pharmacokinetics.更多还原