Chen Feng, Hu Zhe-Yi, Laizure S Casey, Hudson Joanna Q
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Bioanalysis. 2017 Mar;9(5):469-483. doi: 10.4155/bio-2016-0157. Epub 2017 Feb 8.
Optimal dosing of antibiotics in critically ill patients is complicated by the development of resistant organisms requiring treatment with multiple antibiotics and alterations in systemic exposure due to diseases and extracorporeal drug removal. Developing guidelines for optimal antibiotic dosing is an important therapeutic goal requiring robust analytical methods to simultaneously measure multiple antibiotics.
An LC-MS/MS assay using protein precipitation for cleanup followed by a 6-min gradient separation was developed to simultaneously determine five antibiotics in human plasma.
The precision and accuracy were within the 15% acceptance range. The formic acid concentration was an important determinant of signal intensity, peak shape and matrix effects.
The method was designed to be simple and successfully applied to a clinical pharmacokinetic study.
重症患者抗生素的最佳剂量确定较为复杂,这是因为耐药菌的出现需要联合使用多种抗生素进行治疗,同时疾病和体外药物清除会导致全身药物暴露量发生改变。制定最佳抗生素剂量指南是一项重要的治疗目标,需要可靠的分析方法来同时测定多种抗生素。
建立了一种液相色谱-串联质谱(LC-MS/MS)分析法,采用蛋白沉淀法进行净化,随后进行6分钟的梯度分离,以同时测定人血浆中的五种抗生素。
精密度和准确度在15%的可接受范围内。甲酸浓度是信号强度、峰形和基质效应的重要决定因素。
该方法设计简单,已成功应用于一项临床药代动力学研究。