LC-MS/MS法测定人血浆中比阿培南浓度  

Determination of concentration of biapenem in human plasma by LC-MS/MS

作　　者：钱亚芳 杨旭萍 蒋艳[1] 胡楠[1] QIAN Ya-fang;YANG Xu-ping;JIANG Yan;HU Nan(Department of Pharmacy,The First People’s Hospital of Changzhou,Changzhou Jiangsu 213003)

机构地区：[1]常州市第一人民医院药学部,江苏常州213003

出　　处：《中南药学》2023年第2期432-436,共5页Central South Pharmacy

基　　金：常州市“十四五”卫生健康高层次人才培养工程(No.KY20221389);常州市科技基础设施建设计划-常州市临床药学重点实验室(No.CM20223005)。

摘　　要：目的 建立LC-MS/MS法测定人血浆中比阿培南的浓度。方法 以法罗培南为内标、乙腈溶液沉淀蛋白并稀释后进样分析。色谱柱为Kinetex HILIC(2.1 mm×50 mm,2.6μm),流动相为0.1%甲酸-水(含10 mmol·L^(-1)乙酸铵)和95%乙腈-水(含10 mmol·L^(-1)乙酸铵),梯度洗脱,进样量为5μL,流速为0.4 mL·min^(-1),分析时间为5 min。采用电喷雾离子源(ESI),正离子多反应监测(MRM)模式扫描,用于定量分析的离子对分别为m/z351.0→110.0(比阿培南)、m/z 308.0→178.0(内标法罗培南)。结果 比阿培南在0.20~50.00μg·mL^(-1)与峰面积线性关系良好(r≥0.9950),准确度为97.80%~111.25%,批内和批间精密度RSD均<15%。提取回收率为80.25%~84.11%,基质效应为109.19%~117.91%。血浆样品室温放置1 h,4℃冰箱放置6 h,-80℃冰箱放置14 d,经过3次冻融循环及处理好的样本于自动进样器(15℃)中放置6 h后,均符合生物样本分析的要求。应用本研究方法测定15例发生感染并使用比阿培南患者的血浆谷浓度,测得比阿培南谷浓度为0.30~11.82μg·mL^(-1)。结论 该法专属性强,准确度和重现性好,分析效率高,适用于比阿培南的临床治疗药物监测。Objective To establish an LC-MS/MS method to determine the concentration of biapenem in human plasma.Methods Faropenem was used as the internal standard and the protein was precipitated with acetonitrile.The chromatographic column was Kinetex HILIC (2.1 mm×50 mm,2.6μm,Phenomenex,USA) with mobile phases consisting of 0.1%formic acid-water (containing10 mmol·L^(-1)ammonium acetate) and 95%acetonitrile-water (containing 10 mmol·L^(-1)ammonium acetate).Gradient elution was performed.The flow rate was 0.4 mL·min^(-1)and the injection volume was 5μL.The analysis time was 5 min.The ion pairs were m/z 351.0→110.0(biapenem) and m/z 308.0→178.0 (faropenem),respectively.Results The linearity of biapenem was 0.20~50.00μg·mL^(-1)(r≥0.9950).The intra-day and inter-day precision were both lower than 15%.The stability of biapenem,including plasma samples placed at room temperature for 1h,in the refrigerator at 4℃for 6 h,in the refrigerator at-80℃for 14 d and after three freezethaw cycles and the treated samples placed in the automatic samplers (15℃) for 6 h,were all met the methodological requirements.The trough concentration of biapenem was measured in 15 patients and the result was 0.30~11.82μg·mL^(-1).Conclusion This method is specific,accurate,and repeatable,which is suitable for clinical monitoring of biapenem.

关 键 词：LC-MS/MS 比阿培南 血药浓度 治疗药物监测 

分 类 号：R96[医药卫生—药理学]