液相色谱-串联质谱法测定微量人血浆中伏立康唑  

LC-MS/MS determination of voriconazole in low-volume human plasma

作　　者：赵晓华[1,2] 钟大放[1] 沈晓红[3] 陈笑艳[1] 

机构地区：[1]中国科学院上海药物研究所,上海201203 [2]山西医科大学,山西太原030001 [3]上海中医药大学附属曙光医院,上海201203

出　　处：《中国新药与临床杂志》2009年第1期43-47,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的建立一种快速、灵敏的液相色谱-串联质谱法(LC-MS/MS)测定微量人血浆中伏立康唑。方法氟康唑为内标(IS),25μL血浆样品经乙醚-二氯甲烷(3∶2,V∶V)萃取,在ZorbaxSB-C18色谱柱(150mm×4.6mmI.D.,5μm,USA)上分离,以乙腈-水-甲酸(80∶20∶0.15,V∶V∶V)为流动相。采用电喷雾电离源(ESI源),在正离子检测方式下,以选择反应监测模式进行定量分析,监测的离子反应分别为m/z350→m/z(127+281)(伏立康唑)和m/z307→m/z(220+238)(氟康唑)。结果本法伏立康唑的线性范围为5.00～5000μg·L-1,定量下限为5.00μg·L-1,提取回收率大于90%(RSD小于6.2%),日内、日间RSD均小于6.6%,RE在(-1.1～1.8)%之间,每一个样品色谱分析时间小于4.5min。结论本方法操作简便、快速、灵敏,成功应用于伏立康唑的药动学研究。AIM To develop and validate a liquid chromatography-tandem mass spectrometry （LC-MS/ MS） method for quantification of voriconazole （VRC） only using 25 uL human plasma. METHODS Voriconazole and the internal standard, fluconazol, were isolated from 25 uL volume of plasma by liquid-liquid extraction with ether-dichloromethane （3 ： 2, V ： V）, then chromatographed on a Zorbax Extend C18 column （150 mm × 4.6 mm I.D., 5 um, USA） using a mobile phase of acetonitrile-water-formic acid （80 ： 20 ： 0.15, V ： V ： V） at a flow rate of 0.50 mL· min^-1. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in positive ion mode. Quantification was performed using selected reaction monitoring （SRM） mode of the transition of m/z 350→m/z （127 ＋ 281 ） for VRC and m/z 307→m/z （220 ＋ 238） for fluconazol （IS）, respectively. RESULTS The complete elution was obtained in less than 4.5 min. The linear concentration ranges of the calibration curves for VRC was 5.00 - 5 000 ug· L^-1. The lower limit of quantitation of VRC was 5.00 ug·L^-1. The average extraction recovery was about 90% （RSD 〈 6.2% ）. The intra-day and inter-day relative standard deviations were less than 6.6%. CONCLUTION The method is accurate, sensitive, and simple for the pharmacokinetic or bioequivalence study of VRC. The accuracy was within （-1.1 - 1.8）%.

关 键 词：伏立康唑 色谱法 高压液相 光谱法 质量 电喷雾电离 血浆药物浓度 

分 类 号：R969.1[医药卫生—药理学] R978.5[医药卫生—药学]