【摘要】 目的:建立同时测定血清中5个三唑类抗真菌药物（氟康唑、伏立康唑、伊曲康唑、羟基伊曲康唑、泊沙康唑）浓度的液相色谱-串联质谱（LC-MS/MS）方法,并应用于临床三唑类抗真菌药物的治疗监测。方法:50μL血清样品加入同位素内标,采用乙腈直接沉淀法处理样品后稀释进样分析。采用XSELECTTM CSHTM C₁₈（2.1 mm×100 mm,3.5μm）色谱柱进行色谱分离,流动相为0.1%甲酸10 mmol·L^-1乙酸铵水溶液-0.1%甲酸乙腈水溶液,梯度洗脱,流速为0.5 m L·min^-1,进样量5μL,色谱分析时间5.5 min;采用电喷雾离子源,反应监测模式,正离子扫描进行测定。结果:5个三唑类抗真菌化合物的线性范围为0.02²0μg·m L^-1,线性相关系数均大于0.998 6,各浓度的批内和批间相对标准差（RSD）<10.6%,提取回收率为80.5%⁹8.4%,方法准确度为87.4%¹11.0%,收集临床ICU和血液科严重侵袭性真菌病20例接受伏立康唑治疗的患者,伏立康唑的血药浓度0.24⁴.06μg·m L^-1,个体间差异较大。结论:本方法同时定量检测5个三唑类抗真菌药物的血药浓度,可应用于临床治疗药物监测。更多还原

【Abstract】 Objective:To develop a liquid chromatography-tandem mass spectrometry（LC-MS/MS）method for simultaneous determination of five azole antifungals（fluconazole,voriconazole,itraconazole,hydroxitraconazole,posaconazole）in human serum and then to apply it to clinical therapeutic drug monitoring.Methods:The serum samples（50 μL）were precipitated with acetonitrile after the addition of isotope internal standards.The chromatographic separation was performed on XSELECTTM CSHTM C₁₈（2.1 mm×100 mm,3.5 μm）with the mobile phase of 10 mmol·L^-1 ammonium acetate solution（containing 0.1% formic acid）-acetonitrile（containing 0.1% formic acid）at a flow rate of 0.5 m L·min^-1.The injection volume was 5 μL and liquid chromatography duration was 5.5 min.The deprotonated ion of analyte was ionized by turbo ion spray and was detected in positive ionization by multiple reaction monitoring mode.Results:The linear concentration ranges of the calibration curves for five azole antifungals were 0.02-20 μg·m L^-1.The coefficients of linearity were more than 0.998 6.Within-batch and between-batch RSD were less than 10.6%.The average recovery ranged from 80.5% to 98.4%.The accuracy ranged from 87.4% to 111.0%.Twenty patients received voriconazole therapy were collected from ICU and hemotology department.Blood concentration of voriconazole ranged from 0.24 μg·m L^-1 to 4.06 μg·m L^-1.Significant variance was found among patients.Conclusion:The method is suitable for quantitative determination of five azole antifungals in clinical therapeutic drug monitoring practice.更多还原