液相色谱-串联质谱法同时测定血清中5个三唑类抗真菌药物浓度及其治疗药物监测应用

发布时间：2018-06-17 00:49

本文选题：氟康唑 + 伏立康唑　；参考：《药物分析杂志》2017年06期

【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 C_(18)(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0.02~20μg·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0.24~4.06μg·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。
[Abstract]:Objective: to establish a liquid chromatography-tandem mass spectrometry (LC-MS) method for simultaneous determination of the concentrations of five triazole antifungal drugs (fluconazole, volconazole, itraconazole, hydroxyitraconazole, posaconazole) in serum. And used in clinical triazole antifungal drug therapy monitoring. Methods 10 渭 L serum samples were treated by direct precipitation of acetonitrile and then diluted with isotopic internal standard. The chromatographic separation was carried out on an XSELECTTM CSHTM C _ (18) column with a mobile phase of 0.1% formic acid 10 mmol / L ~ (-1) ammonium acetate aqueous solution -0.1% acetonitrile solution, gradient elution, flow rate of 0.5 mL / min, injection volume of 5 渭 L and chromatographic analysis time of 5.5 min. Reaction monitoring mode, positive ion scanning for determination. Results: the linear range of the five triazole antifungal compounds was 0.02 ~ 20 渭 g / L ~ (-1), the linear correlation coefficient was more than 0.998, the relative standard deviation (RSD) of each concentration was 10.6, the recovery rate was 80.5 ~ 98.4, the accuracy of the method was 87.4 渭 g / L ~ (-1). The clinical ICU and hematology department were collected. 20 patients with severe invasive mycosis treated with Volconazole, The plasma concentration of voliconazole was 0.24 渭 g / L, 4.06 渭 g / L, and there was significant difference among individuals. Conclusion: this method can be used to monitor the clinical treatment of 5 triazole antifungal drugs.
【作者单位】：上海大学生命科学学院;上海市徐汇区中心医院/复旦大学附属中山医院徐汇医院;中国科学院上海临床研究中心;
【分类号】：R969

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