摘要
目的：建立超快速液相色谱-串联质谱（UHPLC-MS/MS）法测定血浆中伏立康唑浓度,开展治疗药物监测。方法：以格列苯脲为内标,采用蛋白沉淀的前处理方法,使用Phenomenex Synergi Hydro-RP色谱柱（2.00 mm×50 mm,4μm）,以0.1%（V/V）甲酸-乙腈和0.1%（v/v）甲酸-水溶液为流动相,流速0.6 ml·min^-1进行梯度洗脱。质谱采用电喷雾离子源（ESI）,以多反应监测（MRM）扫描模式,在正离子电离模式下进行测定,伏立康唑和格列苯脲的定量分析离子分别为m/z 350.0/281.0和m/z 494.2/369.1。结果：血浆中无干扰测定的内源性物质,线性范围为0.1-20μg·ml^-1,r^2=0.999 3,相对回收率为88.34%-101%,高、中、低日内精密度（RSD）〈7.01%,日间精密度（RSD）〈8.96%,提取回收率,基质效应、稳定性均通过方法学验证。结论：该方法简单快速、准确、灵敏度高,适用于伏立康唑的治疗药物监测。
OBJECTIVE To establish a rapid,sensitive and accurate ultra-high performance liquid chromatography method for the determination of voriconazole in human plasma and to apply this method for therapeutic drug monitoring of voriconazole.METHODS The LC-MS /MS was applied for determination of voriconazole plasma concentration with glibenclamide as internal standard.The mobile phase consisted of 0.1% formic acid in acetonitrile and 0.1% formic acid in water and was pumped at a flow rate of 0.6 ml·min^-1in gradient elution.Quantitative analysis was conducted in the multiple reaction monitoring modes with product ion transitions of m /z 350.011 /281.018 and m /z 494.2 /369.1 for voriconazole and internal standard,respectively.RESULTS Chromatograms showed no endogenous interfering peaks in the respective blank human plasma samples.The calibration was linear in the concentration range of 0.1 - 20 μg·ml^-1（r^2= 0.9993） and the recoveries were at 88.34% - 101.3%.Inter-day and intra-day RSD was less than7.01% and 8.96%,respectively.The extraction recovery,matrix effect and stability were validated for voriconazole in human plasma.CONCLUSION This method is simple,rapid,specific and precise for the determination of voriconazole in human plasma.It could be widely used for TDM study of voriconazole.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2014年第20期1748-1751,共4页
Chinese Journal of Hospital Pharmacy
