Identification of the urinary metabolites of glionitrin A in rats using ultra-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry
Identification of the urinary metabolites of glionitrin A in rats using ultra-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry
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DOI：
10.1016/j.jchromb.2012.08.015
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发表时间：
2012-10-01
影响因子：
3
通讯作者：
Jung, Byung Hwa
中科院分区：
文献类型：
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作者：
Lee, Soo Hyun;Yang, Hyun Ok;Jung, Byung Hwa
Glionitrin A（GN A）是从烟曲霉真菌菌株和鞘氨醇单胞菌菌株共培养物中分离得到的一种新的二硫代哌嗪二酮化合物。在大鼠中静脉内施用GN A后，使用超高效液相色谱/四极杆飞行时间质谱（UPLC-QTOP-MS）分析结合数据处理程序如MetaboLynx（TM）和MassFragnent（TM）鉴定了GN A的13种尿代谢物。还原、硝基还原和水合作用是影响体内GN A的主要代谢过程，其次是脱甲基或氧化脱氨基形成醇，以及半胱氨酸、甘氨酸、葡糖苷酸或硫酸盐结合。发现还原产生的代谢物是具有二硫醇基团的分子，并且发现通过硝基还原产生的代谢物是对应于GN A的芳香胺。这两种产品都可能具有药理学或毒理学活性，这对于使用GN A作为先导化合物是有价值的信息。此外，这项工作表明，UPLC-QTOP-MS分析与有效的数据处理程序相结合，可用于快速和可靠地表征体内的GN A代谢物。(C)2012 Elsevier B. V.保留所有权利。
Glionitrin A (GN A) is a new diketopiperazine disulfide with an aromatic nitro group, which is isolated from the coculture of an Aspergillus fumigatus fungal strain and a Sphingomonas bacterial strain. After intravenous administration of GN A in rats, 13 urinary metabolites of GN A were identified using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectroscopy (UPLC-QTOP-MS) analysis in conjunction with data processing programs such as MetaboLynx (TM) and MassFragnent (TM). Reduction, nitro-reduction and hydration were the primary metabolic processes affecting GN A in vivo, followed by demethylation or oxidative deamination to alcohol, as well as cysteine, glycine, glucuronide or sulfate conjugation. The metabolite resulting from reduction was found to be a molecule with a dithiol group, and the metabolite made by nitro reduction was found to be an aromatic amine corresponding to GN A. Both of these products may have pharmacological or toxicological activity, which is valuable information in terms of using GN A as a lead compound. In addition, this work showed that UPLC-QTOP-MS analysis coupled with efficient data processing programs is useful for rapid and reliable characterization of GN A metabolites in vivo. (C) 2012 Elsevier B.V. All rights reserved.