超高效液相色谱质谱联用法测定儿童血浆中利福平、利福喷丁和利福布汀的浓度研究

Simultaneous determination of rifampicin, rifapentine and rifabutine in child plasma by UPLC-MS/MS

目的：建立超高效液相色谱质谱联用法（ UPLC－MS／MS）同时测定儿童血浆中利福平、利福喷丁和利福布汀的浓度方法。方法以扎来普隆为内标，血浆样品经乙腈沉淀蛋白处理后检测。 ACQUITY UPLC HSS T3色谱柱（2．1 mm ×100 mm，1．8μm）为分析柱，以乙腈－水（15 mmol· L－1甲酸铵－0．05％甲酸）为流动相，梯度洗脱，用电喷雾离子化源（ESI），以正离子多反应监测（MRM），检测专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性。结果利福平、利福喷丁和利福布汀的线性范围分别为100～5000，20～2000，20～2000 ng· mL －1。日内、日间精密度相对标准偏差（ RSD ）均小于15％。结论本法灵敏、简便、准确，可同时对利福平、利福喷丁及利福布汀进行治疗药物监测。

Objective To establish a method for the simultaneous deter-mination of rifampicin, rifapentine and rifabutine in child plasma by UPLC-MS/MS.Methods Zaleplon was used as internal standard. The proteins of plasma samples were precipitated with acetonitrile.The fluid was separated on the ACQUITY UPLC HSS T3 column （ 2.1 mm × 100 mm,1.8 μm） .The mobile phase consisted of acetonitrile and 15 mol· L-1 ammonium formate -0.05% formic acid solution in gradient elution.Electrospray ionization （ ESI） source was applied and operated in the positive multiple reaction monitoring （ MRM） mode.The specificity, standard curve and lower limit of quantitation, precision and recovery rate and stability as well as the matrix effect were investigated.Results The linear ranges of rifampicin, rifapentine, rifabutine were 100-5000, 20-2000, 20-2000 ng· mL-1 , respectively.The intra-day and inter-day precision （ RSDs） were less than 15%.Conclusion The method is sensi-tive, simple and accurate.The therapeutic drug monitoring of three antitu-berculosis drugs could be performed at the same time.