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| Metabolism of Mequindox in Isolated Rat Liver Cells |
| LIGuang-hui12, SHANQi1, WANGJing1, LIYa-fei1, GAOYan1, ZENGZhen-ling1 |
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 |
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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.
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.
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Received: 10 August 2012
Accepted:
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| Fund: The work was financially supported by the National Basic Research Program of China (2009CB118800) |
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Corresponding Authors:
ZENG Zhen-ling, Tel: +86-20-85281204, Fax: +86-20-85284896, E-mail: zlzeng@scau.edu.cn
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| About author: ZENG Zhen-ling, Tel: +86-20-85281204, Fax: +86-20-85284896, E-mail: zlzeng@scau.edu.cn |
Cite this article:
LIGuang-hui12 , SHANQi1 , WANGJing1 , LIYa-fei1 , GAOYan1 , ZENGZhen-ling1 .
2014.
Metabolism of Mequindox in Isolated Rat Liver Cells. Journal of Integrative Agriculture, 13(1): 158-166.
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