High-resolution mass spectrometry (HRMS) is an important technology for studying biotransformations of drugs in biological systems. In order to process complex HRMS data, bioinformatics, including data-mining techniques for identifying drug metabolites from liquid chromatography/high-resolution mass spectrometry (LC/HRMS) or multistage mass spectrometry (MSn ) datasets as well as elucidating the detected metabolites' structure by spectral interpretation software, are important tools. Data-mining technologies have widely been used in drug metabolite identification, including mass defect filters, product ion filters, neutral-loss filters, control sample comparisons and extracted ion chromatographic analysis. However, the metabolites identified by current different technologies are not the same, indicating the importance of technique integration for efficient and complete identification of metabolic products. In this study, a universal, high-throughput workflow for identifying and verifying metabolites by applying the drug metabolite identification software UNIFI is reported, to study the biotransformation of verapamil in rats. A total of 71 verapamil metabolites were found in rat plasma, urine and faeces, including two metabolites that have not been reported in the literature. Phase I metabolites of verapamil were identified as N-demethylation, O-demethylation, N-dealkylation and oxidation and dehydrogenation metabolites; phase II metabolites were mainly glucuronidation and sulfate conjugates, indicating that UNIFI software could be effective and valuable in identifying drug metabolites.

译文

高分辨率质谱 (HRMS) 是研究生物系统中药物生物转化的重要技术。为了处理复杂的HRMS数据,生物信息学,包括用于从液相色谱/高分辨率质谱 (LC/HRMS) 或多级质谱 (MSn) 数据集识别药物代谢物的数据挖掘技术以及阐明检测到的代谢物的数据挖掘技术。通过光谱解释软件的结构,是重要的工具。数据挖掘技术已广泛用于药物代谢物鉴定,包括质量缺陷过滤器,产物离子过滤器,中性损耗过滤器,对照样品比较和提取的离子色谱分析。但是,当前不同技术鉴定的代谢物并不相同,这表明技术集成对于有效和完整鉴定代谢产物的重要性。在这项研究中,报告了一种通用的高通量工作流,用于通过应用药物代谢物识别软件UNIFI来识别和验证代谢物,以研究维拉帕米在大鼠中的生物转化。在大鼠血浆,尿液和粪便中总共发现了71种维拉帕米代谢物,其中包括文献中未报道的两种代谢物。维拉帕米的I期代谢产物被鉴定为N-去甲基化,O-去甲基化,N-脱烷基化以及氧化和脱氢代谢产物; II期代谢产物主要是葡萄糖醛酸化和硫酸盐结合物,表明UNIFI软件可以有效地识别药物代谢产物。

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