高效液相色谱-串联质谱法同时测定奈韦拉平、拉米夫定、司他夫定、齐多夫定和依非韦伦的血药浓度  

Determination the concentration of nevirapine,lamivudine,stavudine,zidovudine,efavirenz in human plasma for simultaneous quantification by HPLC-MS/MS

作　　者：张丽军[1] 姚亚敏[1] 孙建军[2] 贾小芳[1] 彭霞[1] 卢洪洲[3] 

机构地区：[1]上海市公共卫生临床中心,上海201508 [2]复旦大学上海医学院,上海200040 [3]复旦大学附属华山医院,上海200433

出　　处：《中国临床药理学杂志》2010年第2期133-136,共4页The Chinese Journal of Clinical Pharmacology

基　　金：卫生部艾滋病防治研究基金资助项目(WA-2007-04)

摘　　要：目的建立高效液相色谱串联质谱技术(HPLC-MS/MS)同时检测奈韦拉平、拉米夫定、司他夫定、齐多夫定和依非韦伦(均为抗艾滋病药)的血药浓度方法。方法用蛋白沉淀法提取,色谱柱为EclipseXDB-C18(4.6mm×150mm,5μm),流动相为(甲醇+0.3%甲酸)-(水+0.3%甲酸)=80∶20,流量为0.5mL·min-1,用质谱多反应监测方法(MRM)检测。结果齐多夫定与拉米夫定的线性范围为25～3200μg.L-1,奈韦拉定与依非韦伦的线性范围为50～6400μg.L-1,最低检测限均为1μg.L-1;司他夫定的线性范围为100～3200μg.L-1,最低检测限为5μg.L-1,γ均大于0.99。高、中、低3个浓度的日内精密度小于10%,日间精密度小于15%,绝对回收率均大于50%。结论用HPLC-MS/MS法能同时快速、准确测定血浆中这5种药物。Objective To establish a liquid chromatography/tandem mass spectrometry （LC - MS/MS） method to determine of nevirapine （NVP） , lamivudine （3TC） , stavudine （d4T） , zidovudine （AZT） and Efavirenz （EFV） for simultaneously quantify in human plasma. Methods After one step protein precipitation, the analytes were chromatographed on a Eclipse XDB - C18（ 150 mm ×4.6 mm, 5 μm） column. An isocratic mobile phase consisting of 0.3% formic acid in water -0. 3% formic acid in methanol （20： 80） was used to separate these five drugs. The precursor and product ions of these drugs were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring mode （MRM） without polarity switch. Results The calibration curves of each drug showed a good linearity in a range of concentration between 25 -3200 μg · L ^-1 for 3TC,AZT,50-6400 μg · L ^-1 for EFV,NVP, 50- 3200 μg · L ^-1 for d4T. The relative recoveries for analysts （above 50% ） achieved from spiked plasma samples were consistent and reproducible. Intra and inter precision （RSD%） were less than 10% and 15% respectively. Conclusion The method was suitable to determine these five AIDS medicine in clinical study under fasting condition.

关 键 词：奈韦拉平 拉米夫定 司他夫定 齐多夫定 依非韦伦 液相色谱-串联质谱 血药浓度 

分 类 号：R969.1[医药卫生—药理学] R986[医药卫生—药学]