Detection and characterization of metabolites in biological matrices using mass defect filtering of liquid chromatography/high resolution mass spectrometry data
Detection and characterization of metabolites in biological matrices using mass defect filtering of liquid chromatography/high resolution mass spectrometry data
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DOI：
10.1124/dmd.106.009241
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发表时间：
2006-10-01
影响因子：
3.9
通讯作者：
Zhang, Haiying
中科院分区：
文献类型：
--
作者：
Zhu, Mingshe;Ma, Li;Zhang, Haiying
一种改进的质量缺陷过滤器（mass defect filter）方法，采用药物和核心结构过滤器模板，应用于高分辨率液相色谱/质谱（LC/MS）数据的处理，用于检测和结构表征的氧化代谢产物的质量缺陷相似或显着不同的母体药物。使用奈法唑酮作为模型化合物研究了这种方法的有效性，已知奈法唑酮会发生多种常见和不常见的氧化反应。通过选择性去除所有落在预设过滤窗口之外的离子，该方法有助于检测MDF过滤色谱图中人肝微粒体中存在的所有14种奈法唑酮代谢物。通过分析人血浆中的奥美拉唑代谢产物，检查了HPLC法从更复杂的生物基质中去除内源性干扰的能力。未处理的质量色谱图未显示代谢产物峰的明显迹象;然而，重复处理后，在色谱图中很容易鉴别代谢产物峰。与前体离子扫描和中性丢失扫描技术相比，该方法被证明是更有效的检测复杂基质中的代谢物。该方法的全面代谢物检测能力，加上准确的质量测定，使高分辨率LC/MS成为筛选和鉴定常见和不常见药物代谢物的有用工具。
An improved mass defect filter ( MDF) method employing both drug and core structure filter templates was applied to the processing of high resolution liquid chromatography/mass spectrometry ( LC/MS) data for the detection and structural characterization of oxidative metabolites with mass defects similar to or significantly different from those of the parent drugs. The effectiveness of this approach was investigated using nefazodone as a model compound, which is known to undergo multiple common and uncommon oxidative reactions. Through the selective removal of all ions that fall outside of the preset filter windows, the MDF process facilitated the detection of all 14 nefazodone metabolites presented in human liver microsomes in the MDF-filtered chromatograms. The capability of the MDF approach to remove endogenous interferences from more complex biological matrices was examined by analyzing omeprazole metabolites in human plasma. The unprocessed mass chromatogram showed no distinct indication of metabolite peaks; however, after MDF processing, the metabolite peaks were easily identified in the chromatogram. Compared with precursor ion scan and neutral loss scan techniques, the MDF approach was shown to be more effective for the detection of metabolites in a complex matrix. The comprehensive metabolite detection capability of the MDF approach, together with accurate mass determination, makes high resolution LC/MS a useful tool for the screening and identification of both common and uncommon drug metabolites.