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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 establish a LC-MS / MS method for the determination of voriconazole in rabbit plasma and to study the pharmacokinetics of voriconazole eye drops in rabbits. Methods The column was CAPCELL CORE ADME C18 column (100 mm × 2.1 mm, 2.7 μm). The mobile phase consisted of acetonitrile with a volume fraction of 0.1% formic acid (60:40 by volume) at a flow rate of 0.2 mL · min- 1. The plasma samples were extracted with ether-methylene chloride (3: 2 by volume) and detected by multiple reaction monitoring (MRM). The concentrations of voriconazole in the plasma of rabbits after monocular administration were measured. Results Voriconazole had a good linearity (r = 0.995 4) within 0.5-100.0 μg · L -1 with a lower limit of quantitation of 0.5 μg · L -1. The intra- and inter-day precision was less than 8.9% The average recovery was (96.8 ± 7.0)% and the matrix effect was (98.1 ± 3.9)% with the accuracy of (-8.0 ~ 1.1)%. The main pharmacokinetic parameters of voriconazole eye drops in rabbit plasma were as follows: t 1/2 (2.9 ± 0.7) h, ρmax 50.8 ± 12.7 μg · L -1 and t max 0.13 ± 0.10) h, AUC0-12h and AUC0-∞ were (57.9 ± 21.4) and (60.7 ± 21.8) μg · h · L -1, respectively. Conclusion This method is suitable for pharmacokinetics of voriconazole eye drops in rabbits.