Department of Pharmacy, The First Hospital of Lanzhou University; and.
Intensive Care Units, The First Hospital of Lanzhou University, Lanzhou, China.
Ther Drug Monit. 2020 Aug;42(4):578-587. doi: 10.1097/FTD.0000000000000736.
Critically ill patients show several pathophysiological alterations that can complicate antibiotic dosing. Hence, there is a strong rationale to individualize anti-infective dosing in these patients by using therapeutic drug monitoring (TDM). The current study aimed to develop and validate a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of total and unbound plasma concentrations of 3 commonly used antibiotics (meropenem, imipenem/cilastatin, and cefoperazone/sulbactam) in the treatment of infections in critically ill patients in China, which could be suitable for routine TDM in hospital laboratories.
The unbound drug was separated from the bound drug by ultrafiltration. Simple protein precipitation was used for sample preparation. Meropenem, imipenem/cilastatin, cefoperazone/sulbactam, and their corresponding internal standards were then resolved using the Waters CORTECS C18 column. All the compounds were detected using electrospray ionization in the positive/negative ion-switching mode.
The calibration curves were linear for all compounds, with correlation coefficients (R) above 0.99 for total concentrations in human plasma and unbound concentrations in the plasma ultrafiltrate. For both total and unbound drugs, the relative errors and intra-assay/interassay relative standard deviations were below 15%. The limit of quantification was 0.05 mcg/mL for both total plasma concentrations and plasma ultrafiltrate concentrations of all compounds.
The method was simple, rapid, and reliable and is currently being used to provide a TDM service to enhance the efficacious use of the 3 antibiotics.
危重症患者表现出多种病理生理改变，这可能会使抗生素的剂量复杂化。因此，通过治疗药物监测（TDM）对这些患者进行个体化抗感染治疗具有很强的合理性。本研究旨在开发和验证一种用于同时测定中国危重症患者感染治疗中 3 种常用抗生素（美罗培南、亚胺培南/西司他丁和头孢哌酮/舒巴坦）总血浆浓度和游离血浆浓度的液相色谱-串联质谱法，该方法适用于医院实验室的常规 TDM。
通过超滤将结合药物与游离药物分离。采用简单的蛋白沉淀法进行样品制备。然后，使用 Waters CORTECS C18 柱对美罗培南、亚胺培南/西司他丁、头孢哌酮/舒巴坦及其相应的内标物进行分离。所有化合物均采用电喷雾电离正/负离子切换模式进行检测。
所有化合物的校准曲线均呈线性，总浓度在人血浆和血浆超滤物中的游离浓度的相关系数（R）均大于 0.99。对于总药物和游离药物，相对误差和日内/日间相对标准偏差均低于 15%。所有化合物的总血浆浓度和血浆超滤物浓度的定量下限均为 0.05 mcg/mL。
该方法简单、快速、可靠，目前正在用于提供 TDM 服务，以提高这 3 种抗生素的疗效。
