Comparison between a high-resolution single-stage Orbitrap and a triple quadrupole mass spectrometer for quantitative analyses of drugs
Comparison between a high-resolution single-stage Orbitrap and a triple quadrupole mass spectrometer for quantitative analyses of drugs
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DOI：
10.1002/rcm.6121
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发表时间：
2012-03-15
影响因子：
2
通讯作者：
Rochat, Bertrand
中科院分区：
文献类型：
--
作者：
Henry, Hugues;Sobhi, Hamid Reza;Rochat, Bertrand
研究了在全扫描质谱模式下运行的高分辨率（HR）、精确质谱（Exactive-MS）用于患者血浆样品中药物的定量LC/MS分析的能力。在m/z 200处的质量分辨率为5万FWHM，质量提取窗口为5？每个分析物的理论m/z附近的PPM用于构建用于定量的色谱图。将Exactive-MS的定量性能与在传统选择反应监测（SRM）模式下工作的三重四极杆质谱仪（TQ-MS）、TSQ Quantum Discovery或Quantum Ultra的定量性能进行比较。研究共使用17种治疗药物，包括8种抗真菌药物（阿尼杜拉芬、卡泊芬、氟康唑、伊曲康唑、羟基伊曲康唑、泊沙康唑、伏立康唑和伏立康唑- n -氧化物），4种免疫抑制剂（环孢素、依维莫司、西罗莫司和他克莫司），5种蛋白激酶抑制剂（达沙替尼、伊马替尼、尼罗替尼、索拉非尼和舒尼替尼）。HR-MS获取的定量结果与SRM获取的检测特异性、分析精密度、准确度、线性度和灵敏度相当。重要的是，HR-MS提供了与TQ-MS技术相比的几个优点：没有SRM优化，在从一个MS更改到另一个MS时节省时间，更完整的样品信息以及更容易的故障排除。我们的研究表明，在常规药物定量分析中，U/HPLC与高效液相色谱-质谱相结合的结果与tq -质谱相当。考虑到HR-MS的优势，这些结果表明，在不久的将来，如何进行小分子常规定量分析，特别是治疗药物的定量分析应该会发生转变。版权所有：John Wiley & Sons， Ltd。
The capabilities of a high-resolution (HR), accurate mass spectrometer (Exactive-MS) operating in full scan MS mode was investigated for the quantitative LC/MS analysis of drugs in patients' plasma samples. A mass resolution of 50 000 (FWHM) at m/z 200 and a mass extracted window of 5?ppm around the theoretical m/z of each analyte were used to construct chromatograms for quantitation. The quantitative performance of the Exactive-MS was compared with that of a triple quadrupole mass spectrometer (TQ-MS), TSQ Quantum Discovery or Quantum Ultra, operating in the conventional selected reaction monitoring (SRM) mode. The study consisted of 17 therapeutic drugs including 8 antifungal agents (anidulafungin, caspofungin, fluconazole, itraconazole, hydroxyitraconazole posaconazole, voriconazole and voriconazole-N-oxide), 4 immunosuppressants (ciclosporine, everolimus, sirolimus and tacrolimus) and 5 protein kinase inhibitors (dasatinib, imatinib, nilotinib, sorafenib and sunitinib). The quantitative results obtained with HR-MS acquisition show comparable detection specificity, assay precision, accuracy, linearity and sensitivity to SRM acquisition. Importantly, HR-MS offers several benefits over TQ-MS technology: absence of SRM optimization, time saving when changing the analysis from one MS to another, more complete information of what is in the samples and easier troubleshooting. Our work demonstrates that U/HPLC coupled to Exactive HR-MS delivers comparable results to TQ-MS in routine quantitative drug analyses. Considering the advantages of HR-MS, these results suggest that, in the near future, there should be a shift in how routine quantitative analyses of small molecules, particularly for therapeutic drugs, are performed. Copyright (c) 2012 John Wiley & Sons, Ltd.