河北医科大学学报 ›› 2022, Vol. 43 ›› Issue (11): 1286-1290.doi: 10.3969/j.issn.1007-3205.2022.11.010

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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

  

  1. 河北省秦皇岛市第一医院药学部，河北 秦皇岛 066000

  • 出版日期:2022-11-25 发布日期:2022-12-28
  • 作者简介:张伟东（1983-），男，河北卢龙人，河北省秦皇岛市第一医院副主任药师，医学博士，从事药物分析和药代动力学研究。
  • 基金资助:
    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）

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

  1. Department of Pharmacy, the First Hospital of Qinhuangdao City, Hebei Province, Qinhuangdao 066000, China
  • Online:2022-11-25 Published:2022-12-28

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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-C18 100A（2.6 μm,4 mm×50 mm）为色谱柱，流动相为甲醇-1‰甲酸水溶液（60〖DK〗∶40,v/v），流速：0.4 mL/min，柱温40 ℃，进样量3 μL。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=4.934×10-5x+2.083×10-2(r=0.999 9)。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。


关键词: 脓毒症, 美罗培南, 液相色谱串联质谱法

Abstract: 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-C18 100A column (2.6 μm, 4 mm× 50 mm) was used, and the mobile phase consisted of methanol-1‰ methanoic acid solution (60〖DK〗∶40, v/v), the flow rate of 0.4 mL/min, the column temperature of 40 ℃ and the injection volume of 3 μL. 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=4.934×10-5x+2.083×10-2 (r=0.999 9). 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. 


Key words: sepsis, meropenem, liquid chromatography tandem mass spectrometry

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