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Analytical and Bioanalytical Chemistry

, Volume 410, Issue 10, pp 2607–2617 | Cite as

Prediction of biotransformation products of the fungicide fluopyram by electrochemistry coupled online to liquid chromatography-mass spectrometry and comparison with in vitro microsomal assays

  • Tessema F. Mekonnen
  • Ulrich Panne
  • Matthias KochEmail author
Research Paper

Abstract

Biotransformation processes of fluopyram (FLP), a new succinate dehydrogenase inhibitor (SDHI) fungicide, were investigated by electrochemistry (EC) coupled online to liquid chromatography (LC) and electrospray mass spectrometry (ESI-MS). Oxidative phase I metabolite production was achieved using an electrochemical flow-through cell equipped with a boron-doped diamond (BDD) electrode. Structural elucidation and prediction of oxidative metabolism pathways were assured by retention time, isotopic patterns, fragmentation, and accurate mass measurements using EC/LC/MS, LC-MS/MS, and/or high-resolution mass spectrometry (HRMS). The results obtained by EC were compared with conventional in vitro studies by incubating FLP with rat and human liver microsomes (RLM, HLM). Known phase I metabolites of FLP (benzamide, benzoic acid, 7-hydroxyl, 8-hydroxyl, 7,8-dihydroxyl FLP, lactam FLP, pyridyl acetic acid, and Z/E-olefin FLP) were successfully simulated by EC/LC/MS. New metabolites including an imide, hydroxyl lactam, and 7-hydroxyl pyridyl acetic acid oxidative metabolites were predicted for the first time in our study using EC/LC/MS and liver microsomes. We found oxidation by dechlorination to be one of the major metabolism mechanisms of FLP. Thus, our results revealed that EC/LC/MS-based metabolic elucidation was more advantageous on time and cost of analysis and enabled matrix-free detection with valuable information about the mechanisms and intermediates of metabolism processes.

Graphical abstract

Oxidative metabolism of fluopyram

Keywords

Metabolism Electrochemical oxidation EC/LC/MS Biotransformation SDHI-fungicide 

Notes

Acknowledgments

The authors would like to thank Mr. Boris Neumann (Proteome Factory AG, Berlin, Germany) for the HRMS measurements.

Funding information

This work was supported by The German Excellence initiative (DFG) program under School of Analytical Sciences Adlershof (SALSA).

Compliance with ethical standards

Conflict of interest

The authors declared that there is no any conflict of interest on this work.

Supplementary material

216_2018_933_MOESM1_ESM.pdf (782 kb)
ESM 1 (PDF 2.54 mb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Tessema F. Mekonnen
    • 1
    • 2
  • Ulrich Panne
    • 1
    • 2
  • Matthias Koch
    • 1
    Email author
  1. 1.Bundesanstalt für Materialforschung und -prüfung (BAM)BerlinGermany
  2. 2.School of Analytical Sciences Adlershof (SALSA)Humboldt-Universität zu BerlinBerlinGermany

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