UPLC-MS/MS法同时测定人血浆中泊沙康唑、氟康唑、伏立康唑的血药浓度

Simultaneous determination of plasma concentrations of posaconazole,fluconazole and voriconazole in human plasma by UPLC-MS/MS

目的:建立UPLC-MS/MS法同时测定血浆中3个三唑类抗真菌药物(泊沙康唑、氟康唑、伏立康唑)的浓度。方法:采用WatersBEHC18(2.1 mm×50 mm,1.7μm)色谱柱,流速0.5 mL/min,流动相为甲醇(含2 mmol/L乙酸铵和0.1%甲酸)和2 mmol/L乙酸铵水溶液(含0.1%甲酸),梯度洗脱,柱温40℃。质谱条件采用电喷雾离子源,正离子多反应监测模式进行扫描分析。结果:泊沙康唑、氟康唑、伏立康唑的专属性良好,线性范围分别为0.083~20.680、0.328~82.075、0.080~20.085μg/mL,范围内线性关系良好,r均大于0.99。批内、批间精密度(RSD)均小于7.60%,提取回收率和基质效应RSD值均小于14.2%,不同储存条件下稳定性良好,RSD值均小于10.69%。结论:该方法准确度高,重复性好,简便快捷,可同时测定3种血浆中三唑类抗真菌药的浓度,适用于临床对氟康唑、泊沙康唑及伏立康唑的治疗药物监测。

Objective:To establish an UPLC-MS/MS method for the simultaneous determination of three triazole antifungal drugs(posaconazole,fluconazole,voriconazole)in plasma.Methods:The chromatographic separation was performed on BEH C18(2.1 mm×50 mm,1.7μm)chromatographic column with methanol(containing 2 mmol/L ammonium acetate and 0.1%formic acid)and 2 mmol/L ammonium acetate Aqueous solution(containing 0.1%formic acid).The column temperature was 40℃.The flow rate was 0.5 mL/min with gradient elution.The mass spectrometry conditions adopt positive electrospray ionization together with multi-reaction monitoring mode for scanning analysis.Results:The specificity of posaconazole,fluconazole and voriconazole was good.The linear ranges were 0.083-20.680,0.328-82.075,0.080-20.085μg/mL,respectively.The linear relationship is good within the range,and r was greater than 0.99.The RSD of intra-batch and inter-batch precision were all less than 7.60%.The RSD of extraction recovery rate and matrix effect were all less than 14.2%.The stability was good under different storage conditions,and the RSD were all less than 10.69%.Conclusion:The method is accurate,repeatableand simple.It can simultaneously determine the concentration of three triazole antifungals in plasma.It is suitable for clinical monitoring of fluconazole,posaconazole and voriconazole.