摘要
目的：建立测定人血浆中伏立康唑浓度的液相色谱-串联质谱联用法。方法：待测血浆0．5mL经乙醚-二氯甲烷萃取，以甲醇-10mmol-L^-1醋酸铵水溶液（80：20）为流动相，流速为1．0mL·min^-1，液相色谱-串联质谱联用法多反应离子检测，正离子模式，用于定量分析的离子分别是伏立康唑m／z351．0→127．0[M＋H^＋]和地西泮m／z285．8→193．3[M＋H^＋]。结果：血浆中无干扰测定的内源性物质，每个样品分析时间小于5min，线性范围为20．0～4000ng·mL^-1，定量下限为20．0ng·mL^-1，批内、批间精密度均小于10％，提取回收率大于85％。结论：该法操作快诛、简单、准确、灵敏唐高，适用于阵床药动学研究。
Objective： To develop a sensitive and specific LC-MS-MS method for determination of voriconazole in human plasma. Methods： Voriconazole was extracted by diethyl ether and dichloromethane from human plasma, then separated on a C18-Column. The mobile phase consisted of methanol and 10 retool· L^-1 ammonium acetate solution （80： 20） and the flow rate was 1.0 mL· min^-1 A mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode. In multiple reaction monitoring （MRM） mode, the ion combinations of m/z 351.0→127.0[ M ＋ H^＋ ] and m/z 285.8→193.3 [ M ＋ H^＋ ] were used to qualify voriconazole and an internal standard （diazapam） , respectively. Results： Chromatograms showed no endogenous interfering peaks in the respective blank human plasma samples. Each analysis was completed within 5 rain. The calibration was linear in the concentration range within 20.0 - 4 000 ng· mL^-1 , and quantitative limit was 20.0 ng·mL^-1 The intra-batch and inter-batch RSDs were less than 10%. The recovery of the extraction was more than 85%. Conclusion： The method is proved to be suitable for clinical investigation of voriconazole pharmacokinetics, which offers advantages of specificity, quickness and higher sensitivity over the previously reported methods.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2008年第2期165-168,共4页
Chinese Journal of New Drugs
