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首页> 外文期刊>Rapid Communications in Mass Spectrometry: RCM >Metabolism of olaquindox in rat liver microsomes: structural elucidation of metabolites by high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry
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Metabolism of olaquindox in rat liver microsomes: structural elucidation of metabolites by high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry

机译：大鼠肝微粒体中喹乙醇的代谢：通过高效液相色谱结合离子阱/飞行时间质谱对代谢产物进行结构解析

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摘要

Olaquindox (N-(2-hydroxyethyl)-3-methyl-2-quinoxalincarboxamide-1,4-dioxide) is a growth-promoting feed additive for food-producing animals. Its toxicity is closely related to the metabolism. The complete metabolic pathways of olaquindox are not revealed. To improve studies of the metabolism and toxicity of olaquindox, its biotransformation in rat liver microsomes and the structure of its metabolites using high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry (LC/MS-ITTOF) were investigated. When olaquindox was incubated with an NADPH-generating system and rat liver microsomes, ten metabolites (M1-M10) were detected. The structures of these metabolites were identified from mass spectra and comparison of their changes in their accurate molecular masses and fragment ions with those of the parent drug. With the high resolution and good mass accuracy achieved by this technique, the elemental compositions of the metabolites and their fragment ions were exactly determined. The results indicate that the N --> O group reduction is the main metabolic pathway of olaquindox metabolism in rat liver microsomes, because abundant 1-desolaquindox (M2), 4-desolaquindox (M1) and bisdesoxyolaquindox (M9) were produced during the incubation step. Seven other minor metabolites were revealed which were considered to be hydroxylation metabolites, based on the position of the quinoxaline ring or 3-methyl group and a carboxylic acid derivative on the side chain at position 2 of the quinoxaline ring. Among the identified metabolites, five new hydroxylated metabolites (M3-M7) were found for the first time in rat liver microsomes. This work will conduce to complete clarification of olaquindox metabolism, and improve the in vivo metabolism of olaquindox in food animals. Copyright (C) 2008 John Wiley & Sons, Ltd.
机译：Olaquindox（N-（2-羟乙基）-3-甲基-2-quinoxalincarboxamide-1,4-dioxide）是用于食品生产动物的促进生长的饲料添加剂。其毒性与代谢密切相关。尚未揭示奥拉喹多的完整代谢途径。为了改进对喹乙醇的代谢和毒性的研究，研究了高效液相色谱结合离子阱/飞行时间质谱（LC / MS-ITTOF）对大鼠喹诺酮在大鼠肝微粒体中的生物转化及其代谢产物的结构的影响。 。当将喹啉与NADPH生成系统和大鼠肝微粒体一起孵育时，检测到十种代谢物（M1-M10）。这些代谢物的结构是通过质谱鉴定的，并将其准确分子质量​​和碎片离子的变化与母体药物的分子质量和碎片离子进行比较。通过该技术实现了高分辨率和良好的质量准确度，可以准确确定代谢物的元素组成及其碎片离子。结果表明，N-> O基团的减少是大鼠肝微粒体中喹乙醇代谢的主要代谢途径，因为在培养过程中会产生大量的1-去甲喹啉（M2），4-去甲喹啉（M1）和双去氧喹啉（M9）步。基于喹喔啉环或3-甲基的位置和喹喔啉环的2位侧链上的羧酸衍生物，揭示了七个其他次要代谢物，它们被认为是羟基化代谢物。在鉴定出的代谢物中，首次在大鼠肝微粒体中发现了五种新的羟基化代谢物（M3-M7）。这项工作将有助于彻底澄清喹乙醇的代谢，并改善食用动物体内喹喹的体内代谢。版权所有（C）2008 John Wiley＆Sons，Ltd.

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