Microanalysis of β-Lactam Antibiotics and Vancomycin in Plasma for Pharmacokinetic Studies in Neonates
Microanalysis of β-Lactam Antibiotics and Vancomycin in Plasma for Pharmacokinetic Studies in Neonates
复制标题
DOI：
10.1128/aac.00636-08
复制
发表时间：
2009-01-01
影响因子：
4.9
通讯作者：
Mathot, Ron A.
中科院分区：
文献类型：
--
作者：
Ahsman, Maurice J.;Wildschut, Enno D.;Mathot, Ron A.
合理给药应基于特定人群的药代动力学（PK）参数。由于血浆总容量有限，限制了样本量和采样频率，阻碍了新生儿PK的研究。现有的药物分析方法需要大量的样品，并且是劳动密集型或耗时的。本研究的目的是建立一种超高效液相色谱-串联质谱检测同时定量50 μ l血浆中阿莫西林、美罗培南、头孢唑林、头孢噻肟、去乙酰头孢噻肟、头孢曲松和万古霉素的方法。清洗包括冷乙腈（1:4）沉淀蛋白质和溶剂蒸发，然后进行反相色谱分离和电喷雾电离串联质谱检测。标准曲线在大的动态范围内制备，有足够的定量限制。组内和组间准确度和精密度分别在100% +/- 15%和15%以内，矩阵效果尚可。6批血浆基质效应和回收率的变异系数均< 10%。血浆和水原液的稳定性一般是足够的，但美罗培南和头孢曲松提取物的稳定性可能会限制自动进样器的容量。每个样品的仪器运行时间约为3.50分钟。用体外膜氧处理新生儿的血浆样本证明了方法的适用性。不同的β -内酰胺类抗生素可以通过额外的离子跃迁添加到该方法中。该方法采用超高效液相色谱-质谱法，可对50 μ l新生儿血浆中多种抗生素进行简单可靠的定量分析。
Rational dosing of antibiotics in neonates should be based on pharmacokinetic (PK) parameters assessed in specific populations. PK studies of neonates are hampered by the limited total plasma volume, which restricts the sample volume and sampling frequency. Available drug assay methods require large sample volumes and are labor-intensive or time-consuming. The objective of this study was to develop a rapid ultra-performance liquid chromatographic method with tandem mass spectrometry detection for simultaneous quantification of amoxicillin, meropenem, cefazolin, cefotaxime, deacetylcefotaxime, ceftriaxone, and vancomycin in 50 mu l of plasma. Cleanup consisted of protein precipitation with cold acetonitrile ( 1: 4) and solvent evaporation before reversed-phase chromatographic separation and detection using electrospray ionization tandem mass spectrometry. Standard curves were prepared over a large dynamic range with adequate limits of quantitation. Intra- and interrun accuracy and precision were within 100% +/- 15% and 15%, respectively, with acceptable matrix effects. Coefficients of variation for matrix effects and recovery were < 10% over six batches of plasma. Stability in plasma and aqueous stocks was generally sufficient, but stability of meropenem and ceftriaxone in extracts could limit autosampler capacity. The instrument run time was approximately 3.50 min per sample. Method applicability was demonstrated with plasma samples from an extracorporeal membrane oxygenation-treated neonate. Different beta-lactam antibiotics can be added to this method with additional ion transitions. Using ultra-performance liquid chromatography mass spectrometry, this method allows simple and reliable quantification of multiple antibiotics in 50 mu l of plasma for PK studies of neonates.