Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs

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Standard

Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs. / Lykkeberg, Anne Kruse; Cornett, Claus; Halling-Sørensen, Bent; Hansen, Steen Honoré.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 42, No. 2, 2006, p. 223-31.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Lykkeberg, AK, Cornett, C, Halling-Sørensen, B & Hansen, SH 2006, 'Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs', Journal of Pharmaceutical and Biomedical Analysis, vol. 42, no. 2, pp. 223-31. https://doi.org/10.1016/j.jpba.2006.03.023

APA

Lykkeberg, A. K., Cornett, C., Halling-Sørensen, B., & Hansen, S. H. (2006). Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs. Journal of Pharmaceutical and Biomedical Analysis, 42(2), 223-31. https://doi.org/10.1016/j.jpba.2006.03.023

Vancouver

Lykkeberg AK, Cornett C, Halling-Sørensen B, Hansen SH. Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs. Journal of Pharmaceutical and Biomedical Analysis. 2006;42(2):223-31. https://doi.org/10.1016/j.jpba.2006.03.023

Author

Lykkeberg, Anne Kruse ; Cornett, Claus ; Halling-Sørensen, Bent ; Hansen, Steen Honoré. / Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs. In: Journal of Pharmaceutical and Biomedical Analysis. 2006 ; Vol. 42, No. 2. pp. 223-31.

Bibtex

@article{f2d3ddd0c69911dd9473000ea68e967b,
title = "Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs",
abstract = "Although the antimicrobial tiamulin is extensively metabolized in pigs, the metabolism is not well investigated. In this work the NADPH dependent metabolism of tiamulin in liver microsomes from pigs has been studied. The tiamulin metabolites formed in the incubations were analysed using LC-MS, and three major metabolites were isolated using solid phase extraction and preparative HPLC. The final structure elucidations were performed by tandem mass spectrometry and (1)H and (13)C NMR. The structures of the metabolites were found to be 2beta-hydroxy-tiamulin, 8alpha-hydroxy-tiamulin and N-deethyl-tiamulin. In addition, the LC-MS chromatograms revealed two other minor metabolites. From their chromatography and from MS(2) analysis the structures were estimated to be 2beta-hydroxy-N-deethyl-tiamulin and 8alpha-hydroxy-N-deethyl-tiamulin, but the structures were not confirmed by NMR. In these studies approximately 20{\%} of tiamulin was deethylated, 10{\%} was hydroxylated in the 2beta-position and 7{\%} was hydroxylated in the 8alpha-position. About 40{\%} of tiamulin was metabolized during the incubation conditions used. The protein precipitation in the incubations was performed using perchloric acid, and the preparative purification was performed under alkaline conditions. Therefore, the stability of the metabolites under these conditions was studied. The metabolites were found to be stable in the acid solution, but under alkaline conditions, particularly at room temperature, the stability of especially 8alpha-hydroxy-tiamulin was considerably reduced (40{\%} loss after 1 week).",
keywords = "The Faculty of Pharmaceutical Sciences",
author = "Lykkeberg, {Anne Kruse} and Claus Cornett and Bent Halling-S{\o}rensen and Hansen, {Steen Honor{\'e}}",
note = "Keywords: Animals; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Chromatography, Liquid; Diterpenes; Female; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolic Detoxication, Drug; Microsomes, Liver; Molecular Structure; NADP; Swine",
year = "2006",
doi = "10.1016/j.jpba.2006.03.023",
language = "English",
volume = "42",
pages = "223--31",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - Isolation and structural elucidation of tiamulin metabolites formed in liver microsomes of pigs

AU - Lykkeberg, Anne Kruse

AU - Cornett, Claus

AU - Halling-Sørensen, Bent

AU - Hansen, Steen Honoré

N1 - Keywords: Animals; Anti-Bacterial Agents; Chromatography, High Pressure Liquid; Chromatography, Liquid; Diterpenes; Female; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolic Detoxication, Drug; Microsomes, Liver; Molecular Structure; NADP; Swine

PY - 2006

Y1 - 2006

N2 - Although the antimicrobial tiamulin is extensively metabolized in pigs, the metabolism is not well investigated. In this work the NADPH dependent metabolism of tiamulin in liver microsomes from pigs has been studied. The tiamulin metabolites formed in the incubations were analysed using LC-MS, and three major metabolites were isolated using solid phase extraction and preparative HPLC. The final structure elucidations were performed by tandem mass spectrometry and (1)H and (13)C NMR. The structures of the metabolites were found to be 2beta-hydroxy-tiamulin, 8alpha-hydroxy-tiamulin and N-deethyl-tiamulin. In addition, the LC-MS chromatograms revealed two other minor metabolites. From their chromatography and from MS(2) analysis the structures were estimated to be 2beta-hydroxy-N-deethyl-tiamulin and 8alpha-hydroxy-N-deethyl-tiamulin, but the structures were not confirmed by NMR. In these studies approximately 20% of tiamulin was deethylated, 10% was hydroxylated in the 2beta-position and 7% was hydroxylated in the 8alpha-position. About 40% of tiamulin was metabolized during the incubation conditions used. The protein precipitation in the incubations was performed using perchloric acid, and the preparative purification was performed under alkaline conditions. Therefore, the stability of the metabolites under these conditions was studied. The metabolites were found to be stable in the acid solution, but under alkaline conditions, particularly at room temperature, the stability of especially 8alpha-hydroxy-tiamulin was considerably reduced (40% loss after 1 week).

AB - Although the antimicrobial tiamulin is extensively metabolized in pigs, the metabolism is not well investigated. In this work the NADPH dependent metabolism of tiamulin in liver microsomes from pigs has been studied. The tiamulin metabolites formed in the incubations were analysed using LC-MS, and three major metabolites were isolated using solid phase extraction and preparative HPLC. The final structure elucidations were performed by tandem mass spectrometry and (1)H and (13)C NMR. The structures of the metabolites were found to be 2beta-hydroxy-tiamulin, 8alpha-hydroxy-tiamulin and N-deethyl-tiamulin. In addition, the LC-MS chromatograms revealed two other minor metabolites. From their chromatography and from MS(2) analysis the structures were estimated to be 2beta-hydroxy-N-deethyl-tiamulin and 8alpha-hydroxy-N-deethyl-tiamulin, but the structures were not confirmed by NMR. In these studies approximately 20% of tiamulin was deethylated, 10% was hydroxylated in the 2beta-position and 7% was hydroxylated in the 8alpha-position. About 40% of tiamulin was metabolized during the incubation conditions used. The protein precipitation in the incubations was performed using perchloric acid, and the preparative purification was performed under alkaline conditions. Therefore, the stability of the metabolites under these conditions was studied. The metabolites were found to be stable in the acid solution, but under alkaline conditions, particularly at room temperature, the stability of especially 8alpha-hydroxy-tiamulin was considerably reduced (40% loss after 1 week).

KW - The Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.jpba.2006.03.023

DO - 10.1016/j.jpba.2006.03.023

M3 - Journal article

VL - 42

SP - 223

EP - 231

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

IS - 2

ER -

ID: 9040317