LC-MS/MS法测定兔血浆中伏立康唑的浓度  

Determination of voriconazole in rabbits plasma by LC-MS/MS

作　　者：李兆琴 张照燕[1] 刘婷[1] 李爽[1] 赵云丽[1] 于治国[1] LI Zhao-qin ZHANG Zhao-yan LIU Ting LI Shuang ZHAO Yun-li YU Zhi-guo(School of Pharmacy,Shenyang Pharmaceutical Universit)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2017年第3期239-243,253,共6页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立LC-MS/MS法测定兔血浆中伏立康唑的浓度,并应用伏立康唑滴眼液在兔体内的药动学研究。方法色谱柱为CAPCELL CORE ADME C18柱(100 mm×2.1 mm,2.7μm),流动相为乙腈-体积分数为0.1%的甲酸水溶液(体积比为60:40),流速为0.2 m L·min-1,采用乙醚-二氯甲烷(体积比为3:2)萃取法处理血浆样品,以多反应监测模式(multiple reaction monitoring,MRM)检测,测定兔单眼单次给药后血浆中的伏立康唑浓度。结果伏立康唑质量浓度在0.5~100.0μg·L^(-1)内线性关系良好(r=0.995 4),定量下限为0.5μg·L^(-1),日内和日间精密度均小于8.9%,准确度在(-8.0~1.1)%内,平均提取回收率(96.8±7.0)%,基质效应为(98.1±3.9)%。伏立康唑滴眼液在家兔血浆中的主要药动学参数:t_(1/2)为(2.9±0.7)h,ρmax为(50.8±12.7)μg·L^(-1),tmax为(0.13±0.10)h,AUC0-12h和AUC0-∞分别为(57.9±21.4)和(60.7±21.8)μg·h·L^(-1)。结论该方法适用于伏立康唑滴眼液在兔体内的药动学研究。Objective To develop an UPLC-MS/MS method for the determination of voriconazole in rabbit plasma,and apply the method to study the pharmaceutical characteristic of voriconazole eye drops in rabbit plasma.Methods After liquid-liquid extraction by diethyl ether-dichloromethane（V：V=3：2）,the separation was achieved on a CAPCELL CORE ADME C_（18） column（100 mm×2.1 mm,2.7μm） using a mobile phase consisting of solvent A（acetonitrile） and solvent B（0.1%formic acid） at a flow rate of 0.2 mL·min（-1）.The plasma concentration after single ocular administration of 10 g·L^-1 voriconazole eye drops to rabbit was detected by multiple reaction monitoring.Results The calibration curve was linear over the range of 0.5-100.0μg·L^-1 and the lower limit of quantification（LLOQ） was 0.5μg·L^-1.The intraand inter-day precision was less than 8.9%,and the accuracy（relative error） of voriconazole was within-（8.0-0.5）%.The average recoveries were（96.8 ±7.0）%and the matrix effects were between（98.1 ±3.9）%.The main pharmacokinetic parameters were as follows：t_（1/2）（2.9 ± 0.7） h,ρ_（max）（50.8 ±12.7）μg·L^-1,t_（max）（0.13 ±0.10）h,AUC_（0-12）（57.9±21.4）μg·h·L^-1,AUC_（0-∞）（60.7 ±21.8）μg·h·L^-1.Conclusions Conclusions This sensitive UPLC-MS/MS method is suitable for determination of voriconazole in plasma of rabbit.

关 键 词：伏立康唑滴眼液 高效液相色谱串联质谱(LC-MS/MS) 药物动力学 

分 类 号：R917[医药卫生—药物分析学]