An algorithm for thorough background subtraction from high-resolution LC/MS data: application for detection of glutathione-trapped reactive metabolites
An algorithm for thorough background subtraction from high-resolution LC/MS data: application for detection of glutathione-trapped reactive metabolites
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DOI：
10.1002/jms.1390
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发表时间：
2008-09-01
影响因子：
2.3
通讯作者：
Yang, Yanou
中科院分区：
文献类型：
--
作者：
Zhang, Haiying;Yang, Yanou
开发了对照样品背景扣除算法，用于在高分辨率、准确的质量液相色谱/质谱（LC/MS）数据中彻底扣除背景和基质相关信号，以揭示分析物样品中的感兴趣离子。该算法在分析物扫描周围的指定时间窗口内检查对照扫描中的所有离子，以潜在减去分析物扫描中发现的离子。应用这种方法，色谱运行之间的波动进行了处理，并在样品中的背景和基质相关的信号可以彻底扣除。使用四种供试化合物（氯氮平、双氯芬酸、丙咪嗪和他克林）证明了该算法的有效性，以在与补充有谷胱甘肽（GSH）的人肝微粒体孵育（30 gm化合物，孵育45分钟）后显示谷胱甘肽（GSH）捕获的反应性代谢物。使用该算法（+/-1.0 min对照扫描时间窗、+/-5 ppm质量误差容限和适当对照样品），GSH捕获的代谢物显示为处理后LC/MS图谱中的主峰。此类图谱允许全面可靠地识别这些代谢物，而无需对其在质谱检测方面的行为或性质进行任何假设。该算法被证明提供上级的结果相比，几个市售的背景减法算法。检测到的许多代谢物是双电荷物质，这将难以用传统的GSH加合物筛选技术检测，因此，一些加合物以前没有在文献中报道。版权所有（C）2008约翰威利父子有限公司
A control sample background-subtraction algorithm was developed for thorough subtraction of background and matrix-related signals in high-resolution, accurate mass liquid chromatography/mass spectrometry (LC/MS) data to reveal ions of interest in an analyte sample. This algorithm checked all ions in the control scans within a specified time window around the analyte scan for potential subtraction of ions found in that analyte scan. Applying this method, chromatographic fluctuations between runs were dealt with and background and matrix-related signals in the sample could be thoroughly subtracted. The effectiveness of this algorithm was demonstrated using four test compounds, clozapine, diclofenac, imipramine, and tacrine, to reveal glutathione (GSH)-trapped reactive metabolites after incubation with human liver microsomes supplemented with GSH (30 gm compound, 45-min incubation). Using this algorithm with a +/- 1.0 min control scan time window, a +/- 5 ppm mass error tolerance, and appropriate control samples, the GSH-trapped metabolites were revealed as the major peaks in the processed LC/MS profiles. Such profiles allowed for comprehensive and reliable identification of these metabolites without the need for any presumptions regarding their behavior or properties with respect to mass spectrometric detection. The algorithm was shown to provide superior results when compared to several commercially available background-subtraction algorithms. Many of the metabolites detected were doubly charged species which would be difficult to detect with traditional GSH adduct screening techniques, and thus, some of the adducts have not previously been reported in the literature. Copyright (C) 2008 John Wiley & Sons, Ltd.