A simple quantitative method analysing amikacin, gentamicin, and vancomycin levels in human newborn plasma using ion-pair liquid chromatography/tandem mass spectrometry and its applicability to a clinical study
A simple quantitative method analysing amikacin, gentamicin, and vancomycin levels in human newborn plasma using ion-pair liquid chromatography/tandem mass spectrometry and its applicability to a clinical study
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DOI：
10.1016/j.jchromb.2014.01.035
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发表时间：
2014-03-01
影响因子：
3
通讯作者：
Mathot, Ron
中科院分区：
文献类型：
--
作者：
Bijleveld, Yuma;de Haan, Timo;Mathot, Ron
神经保护控制的低温治疗是围产期窒息新生儿的标准护理方法。抗生素药物，如阿米卡星、庆大霉素和万古霉素，经常在受控低温下给药，这可能会改变它们的药代动力学 (PK) 和药效 (PD) 特征。为了检查这种效应，开发了一种同时定量血浆中阿米卡星、主要庆大霉素成分（庆大霉素 C、C1a 和 C2）以及万古霉素的 LC-MS/MS 方法。用三氯乙酸 (TCA) 沉淀 25 μL 血浆蛋白，并使用离子对反相色谱法结合电喷雾电离串联质谱法实现成分检测。每个样品的色谱运行时间为 7.5 分钟。阿米卡星和庆大霉素的校准标准品范围为 0.3-50 mg L-1，万古霉素的校准标准品范围为 1.0-100 mg L-1。 LLOQ 准确度在 103% 到 120% 之间，不精确度小于 19%。对于高于 LLOQ 的浓度，准确度范围为 98% 至 102%，不精确度小于 6%。工艺效率、电离效率和回收率是可以接受的。样品和储备溶液在检测的时间段和不同温度下都是稳定的。通过分析 3 名新生儿患者的血浆样本，证明了该方法的适用性。所开发的方法可以准确、精确地同时定量小体积（25 μL）血浆中的阿米卡星、庆大霉素和万古霉素。 (C) 2014 Elsevier B.V. 保留所有权利。
Neuroprotective controlled therapeutic hypothermia is the standard of care for newborns suffering perinatal asphyxia. Antibiotic drugs, such as amikacin, gentamicin, and vancomycin are frequently administered during controlled hypothermia, which possibly alters their pharmacokinetic (PK) and pharmacodynamic (PD) profiles. In order to examine this effect an LC-MS/MS method for the simultaneous quantification of amikacin, the major gentamicin components (gentamicin C, Cl a and C2), and vancomycin in plasma was developed. In 25 mu L plasma proteins were precipitated with trichloroacetic acid (TCA) and detection of the components was achieved using ion-pair reversed phase chromatography coupled with electrospray ionization tandem mass spectrometry. The chromatographic runtime was 7.5 min per sample. Calibration standards were prepared over a range of 0.3-50 mg L-1 for amikacin and gentamicin and 1.0-100 mg L-1 for vancomycin. At LLOQ accuracy was between 103 and 120% and imprecision was less than 19%. For concentrations above LLOQ accuracy ranged from 98% to 102% and imprecision was less than 6%. Process efficiency, ionization efficiency, and recovery were acceptable. Samples and stock solutions were stable during the time periods and at the different temperatures examined. The applicability of the method was shown by analysing plasma samples from 3 neonatal patients. The developed method allows accurate and precise simultaneous quantification of amikacin, gentamicin, and vancomycin in a small volume (25 mu L) of plasma. (C) 2014 Elsevier B.V. All rights reserved.