Journal of Integrative Agriculture ›› 2014, Vol. 13 ›› Issue (1): 158-166.DOI: 10.1016/S2095-3119(13)60335-4

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Metabolism of Mequindox in Isolated Rat Liver Cells

 LIGuang-hui12, SHANQi1, WANGJing1, LIYa-fei1, GAOYan1, ZENGZhen-ling1   

  1. 1.National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University,
    Guangzhou 510642, P.R.China
    2.Jie Yang Entry-Exit Inspection and Quarantine Bureau, Jieyang 522031, P.R.China
  • 收稿日期:2012-08-10 出版日期:2014-01-01 发布日期:2014-01-04
  • 通讯作者: ZENG Zhen-ling, Tel: +86-20-85281204, Fax: +86-20-85284896, E-mail: zlzeng@scau.edu.cn
  • 作者简介:ZENG Zhen-ling, Tel: +86-20-85281204, Fax: +86-20-85284896, E-mail: zlzeng@scau.edu.cn
  • 基金资助:

    The work was financially supported by the National Basic Research Program of China (2009CB118800)

Metabolism of Mequindox in Isolated Rat Liver Cells

 LIGuang-hui12, SHANQi1, WANGJing1, LIYa-fei1, GAOYan1, ZENGZhen-ling1   

  1. 1.National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University,
    Guangzhou 510642, P.R.China
    2.Jie Yang Entry-Exit Inspection and Quarantine Bureau, Jieyang 522031, P.R.China
  • Received:2012-08-10 Online:2014-01-01 Published:2014-01-04
  • Contact: ZENG Zhen-ling, Tel: +86-20-85281204, Fax: +86-20-85284896, E-mail: zlzeng@scau.edu.cn
  • About author:ZENG Zhen-ling, Tel: +86-20-85281204, Fax: +86-20-85284896, E-mail: zlzeng@scau.edu.cn
  • Supported by:

    The work was financially supported by the National Basic Research Program of China (2009CB118800)

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摘要： Mequindox (MEQ), 3-methyl-2-quinoxalinacetyl-1,4-dioxide, is widely used in Chinese veterinary medicine as an antimicrobial agent and feed additive. Its toxicity has been reported to be closely related to its metabolism. To understand the pathways underlying MEQ’s metabolism more clearly, we studied its metabolism in isolated rat liver cells by using liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap (LC-LTQ-Orbitrap) mass spectrometry. The structures of MEQ metabolites and their product ions were readily and reliably characterized on the basis of accurate MS2 spectra and known structure of MEQ. Eleven metabolites were detected in isolated rat liver cells, two of which were detected for the first time in vitro. The major metabolic pathways reported previously for in vitro metabolism of MEQ in rat microsomes were confirmed in this study, including N → O group reduction, carbonyl reduction, and methyl monohydroxylation. In addition, we found that acetyl hydroxylation was an important pathway of MEQ metabolism. The results also demonstrate that cellular systems more closely simulate in vivo conditions than do other in vitro systems such as microsomes. Taken together, these data contribute to our understanding of the in vivo metabolism of MEQ.

关键词: mequindox , isolated rat liver cells , metabolism , metabolites , LC-LTQ-Orbitrap

Abstract: Mequindox (MEQ), 3-methyl-2-quinoxalinacetyl-1,4-dioxide, is widely used in Chinese veterinary medicine as an antimicrobial agent and feed additive. Its toxicity has been reported to be closely related to its metabolism. To understand the pathways underlying MEQ’s metabolism more clearly, we studied its metabolism in isolated rat liver cells by using liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap (LC-LTQ-Orbitrap) mass spectrometry. The structures of MEQ metabolites and their product ions were readily and reliably characterized on the basis of accurate MS2 spectra and known structure of MEQ. Eleven metabolites were detected in isolated rat liver cells, two of which were detected for the first time in vitro. The major metabolic pathways reported previously for in vitro metabolism of MEQ in rat microsomes were confirmed in this study, including N → O group reduction, carbonyl reduction, and methyl monohydroxylation. In addition, we found that acetyl hydroxylation was an important pathway of MEQ metabolism. The results also demonstrate that cellular systems more closely simulate in vivo conditions than do other in vitro systems such as microsomes. Taken together, these data contribute to our understanding of the in vivo metabolism of MEQ.

Key words: mequindox , isolated rat liver cells , metabolism , metabolites , LC-LTQ-Orbitrap