Hydrophilic interaction chromatography/tandem mass spectrometry for the simultaneous determination of three polar non-structurally related compounds, imipenem, cilastatin and an investigational β-lactamase inhibitor, MK-4698, in biological matrices
Hydrophilic interaction chromatography/tandem mass spectrometry for the simultaneous determination of three polar non-structurally related compounds, imipenem, cilastatin and an investigational β-lactamase inhibitor, MK-4698, in biological matrices
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DOI：
10.1002/rcm.4138
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发表时间：
2009-07-01
影响因子：
2
通讯作者：
Woolf, Eric J.
中科院分区：
文献类型：
--
作者：
Xu, Yang;Xie, Wei;Woolf, Eric J.
开发了一种将亲水相互作用色谱 (HILIC) 与串联质谱 (MS/MS) 相结合的方法，用于同时测定大鼠血浆、猴血浆和小鼠血液中的三种极性非结构相关化合物 - 碳青霉烯类抗生素亚胺培南 (IMP)、肾脱氢肽酶抑制剂西司他丁 (CIL) 和研究中的 β-内酰胺酶抑制剂 MK-4698 (BLI)。通过蛋白质沉淀提取分析物，在 Waters Atlantis HILIC 柱上进行色谱分析，并在 Sciex API4000 质谱仪上使用 Turbo-Ion Spray 离子源以正电离模式进行多反应监测 (MRM) 检测。 IMP、CIL 和 BLI 的测定动态范围分别为 0.1-100 μg/mL，总共使用 20-25 μL 生物样品，总 HPLC/MS/MS 运行时间为 4 分钟/注射。该测定被发现具有灵敏性、选择性和可重复性。解决并讨论了样品稳定性、血液样品处理、猴子研究样品中的基质效应以及有限小鼠血液样品的稀释重新分析等挑战。该技术可以快速分析生物基质中的极性化合物，并具有令人满意的色谱保留和增加的通量。版权所有 (C) 2009 John Wiley & Sons, Ltd.
A method coupling hydrophilic interaction chromatography (HILIC) with tandem mass spectrometry (MS/MS) has been developed for the simultaneous determination of three polar non-structurally related compounds - a carbapenem antibiotic, imipenem (IMP), a renal dehydropeptidase inhibitor, cilastatin (CIL), and an investigational beta-lactamase inhibitor, MK-4698 (BLI), in rat plasma, monkey plasma and mouse blood. The analytes were extracted through protein precipitation, chromatographed on a Waters Atlantis HILIC column, and detected on a Sciex API4000 mass spectrometer using a Turbo-Ion Spray ion source in positive ionization mode following multiple-reaction monitoring (MRM). The assay dynamic range was 0.1-100 mu g/mL for IMP, CIL and BLI, respectively, using a total of 20-25 mu L biologic samples, and the total HPLC/MS/MS run time was 4 min/injection. The assay was found to be sensitive, selective and reproducible. The challenges, namely, sample stability, blood sample processing, matrix effect in monkey study samples, and dilution re-assays for the limited mouse blood samples, are resolved and discussed. This technique allowed rapid analysis of polar compounds in biologic matrixes with satisfactory chromatographic retention and increased throughput. Copyright (C) 2009 John Wiley & Sons, Ltd.