A novel reversed-phase high-performance liquid chromatographic assay for the simultaneous determination of imipenem and meropenem in human plasma and its application in TDM
A novel reversed-phase high-performance liquid chromatographic assay for the simultaneous determination of imipenem and meropenem in human plasma and its application in TDM
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DOI：
10.1016/j.jpba.2019.01.039
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发表时间：
2019-05-30
影响因子：
3.4
通讯作者：
Yin, Tao
中科院分区：
文献类型：
--
作者：
Zou, Le;Meng, Fanqi;Yin, Tao
建立了一种快速、特异的反相高效液相色谱法（RP-HPLC），用于同时测定人血浆中亚胺培南和美罗培南的浓度。采用乙腈-二氯甲烷蛋白质沉淀法进行提取，质控品回收率> 91.5%。采用等度洗脱，然后乙腈和水的梯度洗脱，在C18分析柱上进行分离。检测波长为298 nm。该方法准确、重现性好（变异系数CV < 8%），可在0.1 ~ 100 μ g/ml的血浆水平范围内定量测定碳青霉烯，不受30种常用处方药的干扰。在-80 ℃、-20 ℃、+4 ℃和室温20 ℃下，在有或没有稳定剂溶液的情况下测定亚胺培南和美罗培南的稳定性。这两种药物在低温下表现出较高的稳定性。添加3-（N-吗啉代）丙磺酸（MOPS）也可增加它们的稳定性。新生儿和成人治疗药物监测（TDM）结果显示亚胺培南和美罗培南谷浓度的个体间和个体内变异性很大，从而证实了TDM的重要性和必要性。对于新生儿患者，亚胺培南20 mg/kg，q12 h（40 mg/kg/d）未能产生显著的治疗效果，调整剂量或频率达到60 mg/kg/d或以上，以维持疗效所需的谷浓度。该方法操作成本低，分离效果好，可用于医院对亚胺培南和美罗培南的常规监测。(C)2019年爱思唯尔出版
A rapid and specific reversed-phase high-performance liquid chromatographic (RP-HPLC) assay with UV detection has been developed and validated for the simultaneous determination of imipenem and meropenem in human plasma. The extraction process was performed through protein precipitation method using acetonitrile and dichloromethane, and the recoveries of quality controls (QCs) were > 91.5%. Isocratic elution followed by gradient elution of acetonitrile and water was employed over a C18 analytical column for separation. The detection was performed at 298 nm. This method was accurate and reproducible (coefficient of variation, CV < 8%), allowing quantification of carbapenem at the plasma-level ranges from 0.1 to 100 mu g/ml without interference of any of the 30 frequently prescribed drugs. Stabilities of imipenem and meropenem were determined with or without stabilizer solutions at -80 degrees C, -20 degrees C, +4 degrees C and room temperature 20 degrees C. These two drugs showed higher stability at the low temperatures. Addition of 3-(N-morpholino) propanesulfonic acid (MOPS) might also increase their stability. The results of therapeutic drug monitoring (TDM) in neonates and adults showed high inter- and intra- individual variabilities in the trough concentrations of imipenem and meropenem, thus confirming the importance and necessity of TDM. For neonatal patients, imipenem 20 mg/kg, q12h (40mg/kg/day) failed to produce significant therapeutic effects, and either the dose or the frequency was adjusted to achieve 60mg/kg/day or above to maintain the trough concentration required for the curative effect. The low operational cost and good separation efficiency would help implement this assay for the routine therapeutic drug monitoring of imipenem and meropenem in hospitals. (C) 2019 Published by Elsevier B.V.