Skip to main content
SpringerLink
Log in

Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Moxidectin (MOX) is a widely used anthelmintic drug for the treatment of internal and external parasites in food-producing and companion animals. Transformation products (TPs) of MOX, formed through metabolic degradation or acid hydrolysis, may pose a potential environmental risk, but only few were identified so far. In this study, we therefore systematically characterized electro- and photochemically generated MOX TPs using high-resolution mass spectrometry (HRMS). Oxidative electrochemical (EC) TPs were generated in an electrochemical reactor and photochemical (PC) TPs by irradiation with UV-C light. Subsequent HRMS measurements were performed to identify accurate masses and deduce occurring modification reactions of derived TPs in a suspected target analysis. In total, 26 EC TPs and 59 PC TPs were found. The main modification reactions were hydroxylation, (de-)hydration, and derivative formation with methanol for EC experiments and isomeric changes, (de-)hydration, and changes at the methoxime moiety for PC experiments. In addition, several combinations of different modification reactions were identified. For 17 TPs, we could predict chemical structures through interpretation of acquired MS/MS data. Most modifications could be linked to two specific regions of MOX. Some previously described metabolic reactions like hydroxylation or O-demethylation were confirmed in our EC and PC experiments as reaction type, but the corresponding TPs were not identical to known metabolites or degradation products. The obtained knowledge regarding novel TPs and reactions will aid to elucidate the degradation pathway of MOX which is currently unknown.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Awasthi A, Razzak M, Al-Kassas R, Harvey J, Garg S. Analytical profile of moxidectin. Profiles Drug Subst Excip Relat Methodol. 2013;38:315–66. https://doi.org/10.1016/B978-0-12-407691-4.00007-1.

    Article  CAS  PubMed  Google Scholar 

  2. Prichard R, Menez C, Lespine A. Moxidectin and the avermectins: consanguinity but not identity. Int J Parasitol Drugs Drug Resist. 2012;2:134–53. https://doi.org/10.1016/j.ijpddr.2012.04.001.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zulalian J, Stout SJ, daCunha AR, Garces T, Miller P. Absorption, tissue distribution, metabolism, and excretion of moxidectin in cattle. J Agric Food Chem. 1994;42(2):381–7. https://doi.org/10.1021/jf00038a028.

    Article  CAS  Google Scholar 

  4. Stout SJ, Dacunha AR, Wu SS, Zulalian J, Afzal J. Moxidectin - characterization of cattle, sheep, and rat in-vitro and in-vivo metabolites by liquid-chromatography tandem mass-spectrometry. J Agric Food Chem. 1994;42(2):388–92. https://doi.org/10.1021/jf00038a029.

    Article  CAS  Google Scholar 

  5. Afzal J, Stout SJ, daCunha AR, Miller P. Moxidectin: absorption, tissue distribution, excretion, and biotransformation of 14C-labeled moxidectin in sheep. J Agric Food Chem. 1994;42(8):1767–73. https://doi.org/10.1021/jf00044a037.

    Article  CAS  Google Scholar 

  6. Alvinerie M, Dupuy J, Eeckhoutte C, Sutra JF, Kerboeuf D. In vitro metabolism of moxidectin in Haemonchus contortus adult stages. Parasitol Res. 2001;87(9):702–4. https://doi.org/10.1007/s004360100408.

    Article  CAS  PubMed  Google Scholar 

  7. Dupuy J, Escudero E, Eeckhoutte C, Sutra J, Galtier P, Alvinerie M. In vitro metabolism of 14C-moxidectin by hepatic microsomes from various species. Vet Res Commun. 2001;25(5):345–54. https://doi.org/10.1023/A:1010686508307.

    Article  CAS  PubMed  Google Scholar 

  8. Afzal J, Burke AB, Batten PL, DeLay RL, Miller P. Moxidectin: metabolic fate and blood pharmacokinetics of 14C-labeled moxidectin in horses. J Agric Food Chem. 1997;45(9):3627–33. https://doi.org/10.1021/jf960981s.

    Article  CAS  Google Scholar 

  9. Perez R, Cabezas I, Sutra JF, Galtier P, Alvinerie M. Faecal excretion profile of moxidectin and ivermectin after oral administration in horses. Vet J. 2001;161(1):85–92. https://doi.org/10.1053/tvjl.2000.0521.

    Article  CAS  PubMed  Google Scholar 

  10. Hentz SG, Fernandes MAM, Del Bianchi M, Reyes FGR, de Souza JKG, Giannotti FM, et al. Faecal excretion of moxidectin in lambs and its persistence in different environmental conditions. Small Rumin Res. 2019;174:26–33. https://doi.org/10.1016/j.smallrumres.2019.02.015.

    Article  Google Scholar 

  11. EMA. Moxidectin-containing veterinary medicines used in cattle, sheep and horses EMEA/V/A/116. 2017.

  12. FDA. Cydectin (moxidectin 0.5%) pour-on for cattle. Environmental Assessment Sheet no AG07187-2. 1997:United State Environment Protection Agency.

  13. Awasthi A, Razzak M, Al-Kassas R, Greenwood DR, Harvey J, Garg S. Isolation and characterization of degradation products of moxidectin using LC, LTQ FT-MS, H/D exchange and NMR. Anal Bioanal Chem. 2012;404(8):2203–22. https://doi.org/10.1007/s00216-012-6393-9.

    Article  CAS  PubMed  Google Scholar 

  14. Bletsou AA, Jeon J, Hollender J, Archontaki E, Thomaidis NS. Targeted and non-targeted liquid chromatography-mass spectrometric workflows for identification of transformation products of emerging pollutants in the aquatic environment. TrAC Trends Anal Chem. 2015;66:32–44. https://doi.org/10.1016/j.trac.2014.11.009.

    Article  CAS  Google Scholar 

  15. ABA B, Fogg LA, Blackwell PA, Blackwell P, Kay P, Pemberton EJ, et al. Veterinary medicines in the environment. Reviews of environmental contamination and toxicology. New York: Springer New York; 2004. p. 1–91.

    Google Scholar 

  16. Ml F, Pérez S, Kantiani L, Barceló D. Fate and toxicity of emerging pollutants, their metabolites and transformation products in the aquatic environment. TrAC Trends Anal Chem. 2008;27(11):991–1007. https://doi.org/10.1016/j.trac.2008.09.010.

    Article  CAS  Google Scholar 

  17. Bartikova H, Podlipna R, Skalova L. Veterinary drugs in the environment and their toxicity to plants. Chemosphere. 2016;144:2290–301. https://doi.org/10.1016/j.chemosphere.2015.10.137.

    Article  CAS  PubMed  Google Scholar 

  18. Dı́az-Cruz MS, López de Alda MJ, Barceló D. Environmental behavior and analysis of veterinary and human drugs in soils, sediments and sludge. TrAC Trends Anal Chem. 2003;22(6):340–51. https://doi.org/10.1016/S0165-9936(03)00603-4.

    Article  CAS  Google Scholar 

  19. Agüera A, Martínez Bueno MJ, Fernández-Alba AR. New trends in the analytical determination of emerging contaminants and their transformation products in environmental waters. Environ Sci Pollut Res. 2013;20(6):3496–515. https://doi.org/10.1007/s11356-013-1586-0.

    Article  CAS  Google Scholar 

  20. Pico Y, Barcelo D. Transformation products of emerging contaminants in the environment and high-resolution mass spectrometry: a new horizon. Anal Bioanal Chem. 2015;407(21):6257–73. https://doi.org/10.1007/s00216-015-8739-6.

    Article  CAS  PubMed  Google Scholar 

  21. Kotthoff L, Keller J, Lörchner D, Mekonnen TF, Koch M. Transformation products of organic contaminants and residues—overview of current simulation methods. Molecules. 2019;24(4). https://doi.org/10.3390/molecules24040753.

  22. Jahn S, Karst U. Electrochemistry coupled to (liquid chromatography/) mass spectrometry--current state and future perspectives. J Chromatogr A. 2012;1259:16–49. https://doi.org/10.1016/j.chroma.2012.05.066.

    Article  CAS  PubMed  Google Scholar 

  23. Portychova L, Schug KA. Instrumentation and applications of electrochemistry coupled to mass spectrometry for studying xenobiotic metabolism: a review. Anal Chim Acta. 2017;993:1–21. https://doi.org/10.1016/j.aca.2017.08.050.

    Article  CAS  PubMed  Google Scholar 

  24. Bruins AP. An overview of electrochemistry combined with mass spectrometry. TrAC Trends Anal Chem. 2015;70:14–9. https://doi.org/10.1016/j.trac.2015.02.016.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Lohmann W, Karst U. Simulation of the detoxification of paracetamol using on-line electrochemistry/liquid chromatography/mass spectrometry. Anal Bioanal Chem. 2006;386(6):1701–8. https://doi.org/10.1007/s00216-006-0801-y.

    Article  CAS  PubMed  Google Scholar 

  27. Fatta-Kassinos D, Vasquez MI, Kummerer K. Transformation products of pharmaceuticals in surface waters and wastewater formed during photolysis and advanced oxidation processes - degradation, elucidation of byproducts and assessment of their biological potency. Chemosphere. 2011;85(5):693–709. https://doi.org/10.1016/j.chemosphere.2011.06.082.

    Article  CAS  PubMed  Google Scholar 

  28. Team RC. R: a language and environment for statistical computing. 2013.

Download references

Author information

Authors and Affiliations

  1. Department of Analytical Chemistry and Reference Materials, Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstätter-Straße 11, 12489, Berlin, Germany

    Lisa Kotthoff, Jan Lisec & Matthias Koch

  2. School of Chemical and Pharmaceutical Sciences, Technological University Dublin (TU Dublin), Kevin Street, Dublin 8, Ireland

    Sarah-Louise O’Callaghan

  3. Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Potsdam, Germany

    Tanja Schwerdtle

Authors
  1. Lisa Kotthoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah-Louise O’Callaghan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan Lisec
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tanja Schwerdtle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthias Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthias Koch.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 1121 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kotthoff, L., O’Callaghan, SL., Lisec, J. et al. Structural annotation of electro- and photochemically generated transformation products of moxidectin using high-resolution mass spectrometry. Anal Bioanal Chem 412, 3141–3152 (2020). https://doi.org/10.1007/s00216-020-02572-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-020-02572-1

Keywords

Search

Navigation