Meropenem is a wide inter-individual variability in the pharmacokinetic, and standard dosing may not be adequate in critically ill patients. Therapeutic drug monitoring is a useful tool to optimize dosing. Meropenem is the amphoteric compound with an isoelectric point of 5.15. The secondary amino group of meropenem is positively charged when pH ≤ 5.4, thus we attempted to separate by strong cation exchange (SCX) column using acetonitrile/25-mM potassium dihydrogen phosphate (pH 3.0; 60:40) as mobile phase, and good peak shape and effective separation obtained. Generally, meropenem were unstable in plasma. We try to investigate stability of plasma samples using the medium QC sample with or without 3-(N-morpholino) propanesulfonic acid (MOPS) as stabilizer solutions at possible conditions during handling and storage. Meropenem showed higher stability at −80°C, and addition of MOPS might increase the short-term and extracted samples stability. This method is suitable for the quantification of meropenem in human plasma from 0.5 to 100 μg/mL. The accuracy was ranged from 96.53 to 101.11% with relative standard deviation ≤ 4.76%. The method has been used for determined 63 critically ill patients treated with meropenem. During the first measurement, 11 patients showed trough levels below the target ranges despite standard dosing. Through continuous or prolonged infusion, 8/11 patients (72.73%) led to adequate trough levels. The described SCX–high-performance liquid chromatography method for meropenem in human plasma is a powerful tool for therapeutic drug monitoring.

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美罗培南强阳离子交换色谱柱与高效液相色谱方法的开发和验证及其在人血浆中的稳定性评价：在治疗药物监测中的应用

美罗培南的药代动力学存在很大的个体差异，标准剂量对于危重患者可能不够。治疗药物监测是优化剂量的有用工具。美罗培南是两性化合物，等电点为5.15。当pH≤5.4时，美罗培南的仲氨基带正电荷，因此我们尝试使用乙腈/25-mM磷酸二氢钾(pH 3.0；60:40)作为流动相，通过强阳离子交换(SCX)柱进行分离，效果良好峰形和获得的有效分离。一般来说，美罗培南在血浆中不稳定。我们尝试使用含有或不含 3-(N-吗啉代)丙磺酸 (MOPS) 的中等 QC 样品作为稳定剂溶液，在处理和储存期间的可能条件下研究血浆样品的稳定性。美罗培南在 -80°C 下表现出更高的稳定性，添加 MOPS 可能会提高短期和提取样品的稳定性。该方法适用于人血浆中0.5至100 μg/mL美罗培南的定量。准确度为96.53%~101.11%，相对标准偏差≤4.76%。该方法已用于测定63例接受美罗培南治疗的危重患者。在第一次测量期间，尽管采用了标准剂量，但仍有 11 名患者的谷值水平低于目标范围。通过连续或长时间输注，8/11的患者（72.73%）达到了足够的谷值水平。所描述的人血浆中美罗培南的 SCX 高效液相色谱方法是治疗药物监测的有力工具。