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

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(2.6μm, 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^-5x+2.083...

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

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 totherapeutic 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.