美罗培南血清浓度测定及在重症感染患者中的临床应用

Concentration of meropenem in the serum of patients with severe infections and clinical evaluation

目的建立HPLC法测定人血清中美罗培南浓度,应用于重症感染患者治疗药物监测,为其制定个体化给药方案提供参考。方法色谱柱为Wondasil C_(18)柱(4.6 mm×150 mm,5μm),内标为替硝唑,流动相为乙腈:0.015 mol·L^(-1) MOPS溶液(p H=7.3)(梯度洗脱),流速为1.0 mL·min^(-1),检测波长为298 nm,柱温为30℃,进样量为20μL。结果美罗培南血药浓度在0.55~79.09μg·mL^(-1)与峰面积线性关系良好(r=0.9997,n=8);高、中、低3种浓度的方法回收率分别为103.2%、104.6%、98.7%;提取回收率分别为88.28%、90.9%、92.6%;日内与日间精密度RSD均小于5%。应用此方法测定6例美罗培南治疗患者血清谷浓度,有1例患者出现谷浓度小于最低抑菌浓度的情况。结论该方法简便、准确、快速、重现性好,适用于美罗培南血药浓度监测和药动学研究。

Objective To establish an HPLC method to determine the concentration of meropenem in human serum, use the method for therapeutic drug monitoring in critically ill patients, and provide reference for the individualized administration of meropenem. Metohds The sample was determined on Wondasil C18 column （4.6 mm×150 mm, 5μm） with the mobile phase consisting of acetonitrile-0.015 mol · L^-1 3-morpholinopropanesulfonic acid （MOPS） （gradient elution） at 1.0 mL · min^-1. Tinidazole was chosen as the internal standard. The detection wavelength was 298 nm, the column temperature was 30 ℃ and the injection volume was 20 μL. Results The concentration of meropenem showed a good linearity at 0.55- 79.09 μg·mL^-1（r=0.9997, n 8）. The method recovery ofmeropenem at high, middle and low concentration was 103.2%, 104.6%, and 98.7%. The extraction recovery of meropenem at high, middle and low concentration was 88.28%, 90.9%, and 92.6%, respectively. The intra-day and inter-day RSD were both below 5%. The method was applied to determine the valley concentration of 6 patients treated with meropenem, and only one patient with meropenem valley concentration less than the minimum inhibitory concentrations. Conclusion The method is simple, accurate, feasible and repeatable, and it is suitable for the serum concentration monitoring and pharmacokinetic study ofmeropenem.