液相色谱-串联质谱法测定人血浆中美罗培南的浓度及其在ICU脓毒症患者治疗药物监测中的应用  

Determination of meropenem concentration in human plasma by LC-MS/MS and its application in therapeutic drug monitoring in ICU patients with sepsis

作　　者：张伟东[1] 张伟威 阎彦[1] 周静芳 程业童 王娜[1] ZHANG Wei-dong;ZHANG Wei-wei;YAN Yan;ZHOU Jing-fang;CHENG Ye-tong;WANG Na(Department of Pharmacy,the First Hospital of Qinhuangdao City,Hebei Province,Qinhuangdao 066000,China)

机构地区：[1]河北省秦皇岛市第一医院药学部,河北秦皇岛066000

出　　处：《河北医科大学学报》2022年第11期1286-1290,共5页Journal of Hebei Medical University

基　　金：河北省博士后基金资助项目(B2021003046);河北省药学会医院药学科研项目(2020-Hbsyxhqn0001)。

摘　　要：目的建立测定人血浆中美罗培南血药浓度的液相色谱-串联质谱(liquid chromatography tandem mass spectrometry,LC-MS/MS)方法,并将该方法应用于重症加强护理病房(intensive care unit,ICU)脓毒症患者治疗药物监测。方法以Kinetex-C18100A(2.6μm,4 mm×50 mm)为色谱柱,流动相为甲醇-1‰甲酸水溶液(60∶40,v/v),流速:0.4 mL/min,柱温40℃,进样量3μL。以卡马西平为内标,采用串联质谱检测器电喷雾离子源(electron spray ionization,ESI),以正离子多离子反应监测(multiple reaction monitoring,MRM)扫描方式进行监测,定量分析离子对分别为m/z 384→141(美罗培南)、m/z 237→194(卡马西平),并将该方法应用于197例次ICU脓毒症患者治疗药物的监测。结果人血浆中美罗培南浓度在0.02~30 mg/L围内线性关系良好,标准曲线方程为y=4.934×10^(-5)x+2.083×10^(-2)(r=0.9999)。批间和批内精密度RSD<3%,回收率为91.96%~100.97%。197例次ICU脓毒症患者血药浓度范围为0~16.33 mg/L。结论本方法简便、快速,敏感度高、专属性强、结果准确,可用于美罗培南在脓毒症患者治疗药物中的监测。Objective To develop a method for determination of meropenem concentration in human plasma by liquid chromatograph tandem mass spectrometry(LC-MS/MS),and to apply it to therapeutic drug monitoring in intensive care unit(ICU)patients with sepsis.Methods The Kinetex-C18100A column(2.6μm,4 mm×50 mm)was used,and the mobile phase consisted of methanol-1‰methanoic acid solution(60∶40,v/v),the flow rate of 0.4 mL/min,the column temperature of 40℃and the injection volume of 3μL.Carbamazepine was used as internal standard,and electron spray ionization(ESI)source was applied and operated in multiple reaction monitoring(MRM)mode.The quantitative analysis transitions were m/z 384→141(meropenem)and m/z 237→194(carbamazepine).The method was applied to 197 ICU patients with sepsis for therapeutic drug monitoring.Results The linearity was good for meropenem in human plasma within the range of 0.02-30 mg/L.The calibration curve was y=4.934×10^(-5)x+2.083×10^(-2)(r=0.9999).The relative standard deviation(RSD)of intra-and inter-precision was less than 3%,and the extraction recovery was 91.96%-100.97%.The range of plasma concentration of meropenem in 197 sepsis patients was 0-16.33 mg/L.Conclusion The method for determining meropenem concentration is simple,fast,sensitive,specific and accurate,which can be used for the therapeutic drug monitoring in patients with sepsis.

关 键 词：脓毒症 美罗培南 液相色谱串联质谱法 

分 类 号：R631[医药卫生—外科学]