Simultaneous quantification of plasma levels of 12 antimicrobial agents including carbapenem, anti-methicillin-resistant Staphylococcus aureus agent, quinolone and azole used in intensive care unit using UHPLC-MS/MS method
Simultaneous quantification of plasma levels of 12 antimicrobial agents including carbapenem, anti-methicillin-resistant Staphylococcus aureus agent, quinolone and azole used in intensive care unit using UHPLC-MS/MS method
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DOI：
10.1016/j.clinbiochem.2021.01.012
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发表时间：
2021-03-14
影响因子：
2.8
通讯作者：
Itoh, Hiroki
中科院分区：
文献类型：
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作者：
Kai, Makoto;Tanaka, Ryota;Itoh, Hiroki
目的：重症监护病房(ICU)的危重病人易患感染性疾病，建议采用经验性治疗。然而，由于多种因素的影响，ICU患者的药代动力学波动较大，其疗效难以预测。这一问题可以通过治疗药物监测发展个性化药物来解决。然而，当不同的药物使用不同的测量系统时，在临床实践中测量是复杂和耗时的。本研究旨在建立一种超高效液相色谱-串联质谱法同时测定ICU中常用的12种抗菌药：多利培南、美罗培南、利奈唑胺、替唑胺、达普霉素、环丙沙星、左氧氟沙星、帕珠沙星、氟康唑、伏立康唑的主要代谢物伏立康唑和泊康唑。设计与方法：血浆蛋白通过加入乙腈和含有50%甲醇的标记物进行沉淀。采用ACQUITY UHPLC CSH C18色谱柱，流动相为水-乙腈(含0.1%甲酸和2 mM甲酸铵)。结果：该方法符合美国食品和药物管理局的分析验证标准。回收率在84.8%以上。基质效应范围为79.1%~119.3%。所有校正曲线均具有良好的线性关系(校准器反算：相对误差
Objectives: Critically ill patients in intensive care unit (ICU) are susceptible to infectious diseases, thus empirical therapy is recommended. However, the therapeutic effect in ICU patients is difficult to predict due to fluctuation in pharmacokinetics because of various factors. This problem can be solved by developing personalized medicine through therapeutic drug monitoring. However, when different measurement systems are used for various drugs, measurements are complicated and time consuming in clinical practice. In this study, we aimed to develop an assay using ultra-high performance liquid chromatography coupled with tandem mass spectrometry for simultaneous quantification of 12 antimicrobial agents commonly used in ICU: doripenem, meropenem, linezolid, tedizolid, daptomycin, ciprofloxacin, levofloxacin, pazufloxacin, fluconazole, voriconazole, voriconazole N-oxide which is a major metabolite of voriconazole, and posaconazole.Design & methods: Plasma protein was precipitated by adding acetonitrile and 50% MeOH containing standard and labeled IS. The analytes were separated with an ACQUITY UHPLC CSH C18 column, under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate.Results: The method fulfilled the criteria of US Food and Drug Administration for assay validation. The recovery rate was more than 84.8%. Matrix effect ranged from 79.1% to 119.3%. All the calibration curves showed good linearity (back calculation of calibrators: relative error