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Drug / Xenobiotic metabolism

 

In drug and xenobiotic metabolism the metabolites are formed instantaneously in the electrochemical cell mimicking the enzymatic biotransformation of the Cytochrome P450 reactions that usually take place in the liver (Phase I reaction). Hereby Electrochemistry becomes a truly biomimetic tool for enzymatic REDOX reactions.

Significant time and cost saving are possible compared to days or weeks using the traditional in-vitro (e.g., microsomes) and/or in-vivo methods (e.g., rodents, human, etc.). No cumbersome isolation form biological matrices (e.g., urine, plasma) is required and there is no longer risk of adsorption/binding to cells or other biological constituents. By adding glutathione after the electrochemical cell, adduct formation (phase II reaction) can be simulated and detected on-line by MS. Further advantages are: generation of intermediates and short-lived, unstable metabolites, no test animals (rodents), no biohazard risk (human liver microsomes).

Electrochemistry/MS vs. In-Vivo and In-Vitro Studies

Phase I metabolism of Tetrazepam

In only a few minutes all major metabolites of Tetrazepam could be generated and identified by on-line EC/LC/MS. Substantial time savings result using ROXY EC for biomimetic oxidation compared to microsomal incubation followed by metabolite extraction or the even more daunting and cumbersome isolation from urine. Ref: A. Baumann, J of Chrom. A, 1216 (2009) 3192


Application Notes

Application Notebook

Posters

  • 221_070_01 - Online EC MS A Powerful Tool for Fast Prediction of Phase I and II Drug Metabolism
  • 221_076_01 - Expanding Role of Electrochemistry Mass Spectrometry in Life Sciences
  • 221_078_01 - Identification of electrochemically synthesized metabolites
  • 221_107_01 - ElectrochemistryMS a Powerful Tool in Drug Metabolism ASMS 2014
  • 221_117_01 - Mimicking Drug Metabolism ElCheMS2015


16304419 - Electrochemical oxidation of fluoroquinolone antibiotics: Mechanism, residual antibacterial activity and toxicity change
Linyan Zhu, Beatrix Santiago-Schübel, Hongxia Xiao, Henner Hollert, Stephan Kueppers; Water Research, 102, 1 October 2016, Pages 52–62

456535 - An efficient laboratory workflow for environmental risk assessment of organic chemicals
Linyan Zhu, Beatrix Santiago-Schübel, Hongxia Xiao, Björn Thiele, Zhiliang Zhu, Yanling Qiu, Henner Hollert, Stephan Küppers; Chemosphere, 131, July 2015, Pages 34–40

219673 - Liquid chromatography/mass spectrometry to study oxidative degradation of environmentally relevant pharmaceuticals by electrochemistry and ozonation
Helene Faber, Holger Lutze, Pablo Lores Lareo, Lisa Frensemeier, Martin Vogel, Torsten C. Schmidt, Uwe Karst; Journal of Chromatography A, 1343, 23 May 2014, Pages 152–159

22819944 - Bottom-up approach for the reaction of xenobiotics and their metabolites with model substances for natural organic matter by electrochemistry-mass spectrometry (EC-MS).
Chen L, Hofmann D, Klumpp E, Xiang X, Chen Y, Küppers S.; Chemosphere. 2012 Nov;89(11):1376-83. doi: 10.1016/j.chemosphere.2012.05.105. Epub 2012 Jul 21.

22525874 - Identification and quantification of potential metabolites of Gd-based contrast agents by electrochemistry/separations/mass spectrometry.
Telgmann L, Faber H, Jahn S, Melles D, Simon H, Sperling M, Karst U.; J Chromatogr A. 2012 Jun 1;1240:147-55. doi: 10.1016/j.chroma.2012.03.088. Epub 2012 Apr 3.

22227746 - Electrochemical oxidation and protein adduct formation of aniline: a liquid chromatography/mass spectrometry study.
Melles D, Vielhaber T, Baumann A, Zazzeroni R, Karst U.; Anal Bioanal Chem. 2012 Apr;403(2):377-84. doi: 10.1007/s00216-011-5673-0. Epub 2012 Jan 8.

21170519 - Electrochemistry-mass spectrometry for mechanistic studies and simulation of oxidation processes in the environment.
Hoffmann T, Hofmann D, Klumpp E, Küppers S.; Anal Bioanal Chem. 2011 Feb;399(5):1859-68. doi: 10.1007/s00216-010-4575-x. Epub 2010 Dec 19.

24300003 - Simulation of metabolic processes of polycyclic aromatic hydrocarbons using electrochemistry/mass spectrometry
Tina Wigger, Lars Buter, Philipp Strohmide and Uwe Karst; ASMS 2014 poster

24300004 - Simulation of redox metabolism
Christophorus et al.; poster

See our support pages for a full list of recent literature