沈阳药科大学学报

2017, v.34;No.254(03) 239-243+253

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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

李兆琴,张照燕,刘婷,李爽,赵云丽,于治国
LI Zhao-qin,ZHANG Zhao-yan,LIU Ting,LI Shuang,ZHAO Yun-li,YU Zhi-guo

摘要(Abstract):

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(KeyWords): 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
voriconazole eye drops;UPLC-MS/MS;pharmacokinetics

Abstract:

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作者(Author): 李兆琴,张照燕,刘婷,李爽,赵云丽,于治国
LI Zhao-qin,ZHANG Zhao-yan,LIU Ting,LI Shuang,ZHAO Yun-li,YU Zhi-guo

DOI: 10.14066/j.cnki.cn21-1349/r.2017.03.008

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