Electrochemistry-mass spectrometry unveils the formation of reactive triclocarban metabolites

A. Baumann, W. Lohmann, T. Rose, K. C. Ahn, B. D. Hammock, U. Karst, Nils Helge Schebb

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is a widely used antibacterial agent in personal care products and is frequently detected as an environmental pollutant in waste waters and surface waters. In this study, we report novel reactive metabolites potentially formed during biotransformation of TCC. The oxidative metabolism of TCC has been predicted using an electrochemical cell coupled online to liquid chromatography and electrospray ionization mass spectrometry. The electrochemical oxidation unveils the fact that hydroxylated metabolites of TCC may form reactive quinone imines. Moreover, a so-far unknown dechlorinated and hydroxylated TCC metabolite has been identified. The results were confirmed by in vitro studies with human and rat liver microsomes. The reactivity of the newly discovered quinone imines was demonstrated by their covalent binding to glutathione and macromolecules, using β-lactoglobulin A as a model protein. The results regarding the capability of the electrochemical cell to mimic the oxidative metabolism of TCC are discussed. Moreover, the occurrence of reactive metabolites is compared with findings from earlier in vivo studies and their relevance in vivo is argued.

Original languageEnglish (US)
Pages (from-to)2130-2138
Number of pages9
JournalDrug Metabolism and Disposition
Volume38
Issue number12
DOIs
StatePublished - Dec 2010

Fingerprint

Electrochemistry
Mass Spectrometry
Imines
Environmental Pollutants
Lactoglobulins
Electrospray Ionization Mass Spectrometry
Liver Microsomes
Biotransformation
Waste Water
triclocarban
Liquid Chromatography
Glutathione
Anti-Bacterial Agents
Water

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Baumann, A., Lohmann, W., Rose, T., Ahn, K. C., Hammock, B. D., Karst, U., & Schebb, N. H. (2010). Electrochemistry-mass spectrometry unveils the formation of reactive triclocarban metabolites. Drug Metabolism and Disposition, 38(12), 2130-2138. https://doi.org/10.1124/dmd.110.034546

Electrochemistry-mass spectrometry unveils the formation of reactive triclocarban metabolites. / Baumann, A.; Lohmann, W.; Rose, T.; Ahn, K. C.; Hammock, B. D.; Karst, U.; Schebb, Nils Helge.

In: Drug Metabolism and Disposition, Vol. 38, No. 12, 12.2010, p. 2130-2138.

Research output: Contribution to journalArticle

Baumann, A, Lohmann, W, Rose, T, Ahn, KC, Hammock, BD, Karst, U & Schebb, NH 2010, 'Electrochemistry-mass spectrometry unveils the formation of reactive triclocarban metabolites', Drug Metabolism and Disposition, vol. 38, no. 12, pp. 2130-2138. https://doi.org/10.1124/dmd.110.034546
Baumann, A. ; Lohmann, W. ; Rose, T. ; Ahn, K. C. ; Hammock, B. D. ; Karst, U. ; Schebb, Nils Helge. / Electrochemistry-mass spectrometry unveils the formation of reactive triclocarban metabolites. In: Drug Metabolism and Disposition. 2010 ; Vol. 38, No. 12. pp. 2130-2138.
@article{f1d733a00a314aaa97262ae462515e9a,
title = "Electrochemistry-mass spectrometry unveils the formation of reactive triclocarban metabolites",
abstract = "Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is a widely used antibacterial agent in personal care products and is frequently detected as an environmental pollutant in waste waters and surface waters. In this study, we report novel reactive metabolites potentially formed during biotransformation of TCC. The oxidative metabolism of TCC has been predicted using an electrochemical cell coupled online to liquid chromatography and electrospray ionization mass spectrometry. The electrochemical oxidation unveils the fact that hydroxylated metabolites of TCC may form reactive quinone imines. Moreover, a so-far unknown dechlorinated and hydroxylated TCC metabolite has been identified. The results were confirmed by in vitro studies with human and rat liver microsomes. The reactivity of the newly discovered quinone imines was demonstrated by their covalent binding to glutathione and macromolecules, using β-lactoglobulin A as a model protein. The results regarding the capability of the electrochemical cell to mimic the oxidative metabolism of TCC are discussed. Moreover, the occurrence of reactive metabolites is compared with findings from earlier in vivo studies and their relevance in vivo is argued.",
author = "A. Baumann and W. Lohmann and T. Rose and Ahn, {K. C.} and Hammock, {B. D.} and U. Karst and Schebb, {Nils Helge}",
year = "2010",
month = "12",
doi = "10.1124/dmd.110.034546",
language = "English (US)",
volume = "38",
pages = "2130--2138",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "12",

}

TY - JOUR

T1 - Electrochemistry-mass spectrometry unveils the formation of reactive triclocarban metabolites

AU - Baumann, A.

AU - Lohmann, W.

AU - Rose, T.

AU - Ahn, K. C.

AU - Hammock, B. D.

AU - Karst, U.

AU - Schebb, Nils Helge

PY - 2010/12

Y1 - 2010/12

N2 - Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is a widely used antibacterial agent in personal care products and is frequently detected as an environmental pollutant in waste waters and surface waters. In this study, we report novel reactive metabolites potentially formed during biotransformation of TCC. The oxidative metabolism of TCC has been predicted using an electrochemical cell coupled online to liquid chromatography and electrospray ionization mass spectrometry. The electrochemical oxidation unveils the fact that hydroxylated metabolites of TCC may form reactive quinone imines. Moreover, a so-far unknown dechlorinated and hydroxylated TCC metabolite has been identified. The results were confirmed by in vitro studies with human and rat liver microsomes. The reactivity of the newly discovered quinone imines was demonstrated by their covalent binding to glutathione and macromolecules, using β-lactoglobulin A as a model protein. The results regarding the capability of the electrochemical cell to mimic the oxidative metabolism of TCC are discussed. Moreover, the occurrence of reactive metabolites is compared with findings from earlier in vivo studies and their relevance in vivo is argued.

AB - Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is a widely used antibacterial agent in personal care products and is frequently detected as an environmental pollutant in waste waters and surface waters. In this study, we report novel reactive metabolites potentially formed during biotransformation of TCC. The oxidative metabolism of TCC has been predicted using an electrochemical cell coupled online to liquid chromatography and electrospray ionization mass spectrometry. The electrochemical oxidation unveils the fact that hydroxylated metabolites of TCC may form reactive quinone imines. Moreover, a so-far unknown dechlorinated and hydroxylated TCC metabolite has been identified. The results were confirmed by in vitro studies with human and rat liver microsomes. The reactivity of the newly discovered quinone imines was demonstrated by their covalent binding to glutathione and macromolecules, using β-lactoglobulin A as a model protein. The results regarding the capability of the electrochemical cell to mimic the oxidative metabolism of TCC are discussed. Moreover, the occurrence of reactive metabolites is compared with findings from earlier in vivo studies and their relevance in vivo is argued.

UR - http://www.scopus.com/inward/record.url?scp=78649564714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649564714&partnerID=8YFLogxK

U2 - 10.1124/dmd.110.034546

DO - 10.1124/dmd.110.034546

M3 - Article

VL - 38

SP - 2130

EP - 2138

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 12

ER -