液相色谱-串联质谱法快速测定人血浆中伊曲康唑  

LC-MS/MS determination of itraconazole in human plasma

作　　者：付淑军[1] 陈笑艳[1] 宋波[1] 钟大放[1] 

机构地区：[1]中国科学院上海药物研究所

出　　处：《药物分析杂志》2007年第11期1693-1697,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立灵敏、快速的液相色谱-串联质谱法测定人血浆中伊曲康唑,并用于药代动力学研究。方法:血浆样品经乙腈沉淀蛋白后,以乙腈-水-甲酸(80:20:0.2,v/v/v)为流动相,流速0.50 mL·min^(-1),Zorbax sB C_(18)柱分离,采用电喷雾电离源,以选择反应监测(SRM)方式进行正离子检测。用于定量分析的离子反应分别为 m/z 705→m/z(392+432)(伊曲康唑)和m/z 256→m/z 167(内标,苯海拉明)。结果:测定血浆中伊曲康唑的线性范围为1.00～1000 ng·mL^(-1),定量下限为1.00 ng·mL^(-1)。日内、日间精密度(RSD)均小于7.2%,准确度(RE)在±3.0%以内。应用本法测得20名健康受试者单剂量口服200mg 伊曲康唑胶囊后的主要药动学参数为:T_(max)(4.25±1.02)h,C_(max)(155.5±73.3)ng·mL^(-1),t_(1/2)(20.4±11.4)h;用梯形法计算,AUC_(0-84h)(2257±1168)ng·h·mL^(-1),AUC_(0-∞)(237.1±1207)ng·h·mL^(-1)。结论:该法选择性强、灵敏度高、操作简便,适用于伊曲康唑的临床药代动力学研究。in human Objective： To develop a sensitive and rapid LC - MS/MS method for direct determination of itraconazole plasma and to study the pharmacokinetics of itraconazole. Methods： Itraconazole and internal standard diphenhydramine were extracted from plasma with protein precipitation by acetonitrile, then separated on a Zorbax SB C18 column. The mobile phase consisted of acetonitrile - water - formic acid （ 80： 20： 0. 2, v/v/v）, at a flow - rate of 0. 50 mL·min^-1. A Thermo Finnigan TSQ Quantum Ultra tandem mass spectrometer equipped with electrospray ionization source was used as detector operated in the positive ion mode. Selected reaction monitoring with the precursor to products ion combinations of m/z 705 to（392 ±432）and m/z 256 to 167 were performed to quantify itraconazole and the internal standard, respectively. Results：The linear calibration curves were obtained in the concentration range of 1.00 - 1000 ng·mL^-1. The lower limit of quantification was 1.00 ng·mL^-1. The inter - and intra -day precision（RSD） was below 7.2%, and the accuracy（RE） was within 3.0% calculated from QC samples. The method was successfully used in pharmacokinetics study of itraconazole in human plasma after oral administration of 200 mg itraconazole. Pharmacokinetic parameters of itraconazole was obtained as follows： Tmax（4.25 ±1.02）h, Cmax （155.5 ±73.3）ng·mL^-1,t1/2 （20. 4 ± 11.4） h;AUC0-84 h （2257 ± 1168）ng·h·mL^-1 ,AUC0-∞（2371± 1207）ng·h·mL^-1. Conclusion：The method is sensitive, rapid, convenient and is proved to be suitable for clinical investigation of itraconazole pharmacokinetics.

关 键 词：伊曲康唑 液相色谱-串联质谱法 血浆药物浓度 

分 类 号：R917[医药卫生—药物分析学]