Skip to main content
SpringerLink
Log in

Identification of biotransformation products of macrolide and fluoroquinolone antimicrobials in membrane bioreactor treatment by ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry

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

Abstract

Ultrahigh-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was applied for the identification of transformation products (TPs) of fluoroquinolone (norfloxacin and ciprofloxacin) and macrolide (azithromycin, erythromycin, and roxitromycin) antimicrobials in wastewater effluents from a Zenon hollow-fiber membrane bioreactor (MBR). The detected TPs were thoroughly characterized using the accurate mass feature for the determination of the tentative molecular formulae and MS-MS experiments for the structural elucidation of unknowns. Several novel TPs, which have not been previously reported in the literature, were identified. The TPs of azithromycin and roxithromycin, identified in MBR effluent, were conjugate compounds, which were formed by phosphorylation of desosamine moiety. Transformation of fluoroquinolones yielded two types of products: conjugates, formed by succinylation of the piperazine ring, and smaller metabolites, formed by an oxidative break-up of piperazine moiety to form the 7-[(2-carboxymethyl)amino] group. A semi-quantitative assessment of these TPs suggested that they might have contributed significantly to the overall balance of antimicrobial residues in MBR effluents and thus to the overall removal efficiency. Determination of TPs during a period of 2 months indicated a conspicuous dynamics, which warrants further research to identify microorganisms involved and treatment conditions leading to their formation.

Proposed structures of the novel transformation products of antimicrobials, formed during MBR wastewater treatment. AZI TP – phosphorylated azithromycin; ROX TP -phosphorylated roxithromycin; NOR TP1 – succinyl norfloxacin; CIP TP1 – succinyl ciprofloxacin; NOR TP2 - 7-[(carboxymethyl)amino]-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid; CIP TP2 - 7-[(carboxymethyl)amino]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

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
Fig. 6

Similar content being viewed by others

References

  1. Kümmerer K (2008) Pharmaceuticals in the environment: sources, fate, effects and risks, 3 rdth edn. Springer, Heidelberg

    Google Scholar 

  2. Zhang XX, Zhang T, Fang HP (2009) Appl Microbiol Biotechnol 82:397–414

    Article  CAS  Google Scholar 

  3. Gobel A, McArdell CS, Joss A, Siegrist H, Giger W (2007) Sci Tot Environ 372:361–371

    Article  Google Scholar 

  4. Gros M, Petrovic M, Ginebreda A, Barcelo D (2010) Environ Int 36:15–26

    Article  CAS  Google Scholar 

  5. Le-Minh N, Khan SJ, Drewes JE, Stuetz RM (2010) Wat Res 44:4295–4323

    Article  CAS  Google Scholar 

  6. Segura PA, Francois M, Gagnon C, Sauve S (2009) Environ Health Perspec 117:675–684

    Article  CAS  Google Scholar 

  7. Sipma J, Osuna B, Collado N, Monclus H, Ferrero G (2010) Desalination 250:653–659

    Article  CAS  Google Scholar 

  8. Kosjek T, Heath E, Petrovic M, Barcelo D (2007) Trends Anal Chem 26:1076–1085

    Article  CAS  Google Scholar 

  9. Garcia-Galan MJ, Diaz-Cruz MS, Barcelo D (2008) Trends Anal Chem 27:1008–1022

    Article  CAS  Google Scholar 

  10. Jung CM, Heinze TM, Strakosha R, Elkins CA, Sutherland JB (2009) J Appl Microbiol 106:564–571

    Article  CAS  Google Scholar 

  11. Vree TB, Schoondermarkvandeven E, Verweyvanwissen CPWGM, Baars AM, Swolfs A, Vangalen PM, Amatdjaisgroenen H (1995) J Chromatogr B 670:111–123

    Article  CAS  Google Scholar 

  12. Hunter RP, Koch DE, Coke RL, Goatley MA, Isaza R (2003) J Vet Pharmacol Therap 26:117–121

    Article  CAS  Google Scholar 

  13. Wetzstein HG, Stadler M, Tichy H-V, Dalhoff A, Karl W (1999) Appl Environ Microbiol 65:1556–1563

    CAS  Google Scholar 

  14. Adjei MD, Heinze TM, Deck J, Freeman JP, Williams AJ, Sutherland JB (2006) Appl Environ Microbiol 72:5790–5793

    Article  CAS  Google Scholar 

  15. Krauss M, Singer H, Hollender J (2010) Anal Bioanal Chem 397:943–951

    Article  CAS  Google Scholar 

  16. Kern S, Fenner K, Singer HP, Schwarzenbach RP, Hollender J (2009) Environ Sci Technol 43:7039–7046

    Article  CAS  Google Scholar 

  17. Plumb R, Castro-Perez J, Granger J, Beattie I, Joncour K, Wright A (2004) Rapid Commun Mass Spectrom 18:2331–2337

    Article  CAS  Google Scholar 

  18. Terzic S, Ahel M (2011) Environ Pollut 159:557–566

    Article  CAS  Google Scholar 

  19. Kosjek T, Zigon D, Kralj B, Heath E (2008) J Chromat A 1215:57–63

    Article  CAS  Google Scholar 

  20. Senta I, Matosic M, Korajlija Jakopovic H, Terzic S, Mijatovic I, Ahel M (Submitted to J Hazard Mater) Removal of antimicrobials using advanced wastewater treatment.

  21. Senta I (2009) Occurrence and behavior of sulfonamides, fluoroquinolones, macrolides and trimethoprim in wastewater and natural water, PhD thesis, Zagreb.

  22. Terzic S, Senta I, Ahel M, Gros M, Petrovic M, Barcelo D, Müller J, Knepper TP, Martí I, Ventura F, Jovancic P, Jabucar D (2008) Sci Tot Environ 399:66–77

    Article  CAS  Google Scholar 

  23. Senta I, Terzic S, Ahel M (2008) Chromatographia 68:747–758

    Article  CAS  Google Scholar 

  24. Zhang Y, Jiang H, Go EP, Desaire H (2006) J Am Mass Spectrom 17: 1282-.

    Google Scholar 

  25. Yang S, Carlson KH (2004) J Chromatogr A 1038:141–1288

    Article  CAS  Google Scholar 

  26. Wetzstein HG, Schneider J, Karl W (2006) Appl Microbiol Biotechnol 71:90–100

    Article  CAS  Google Scholar 

  27. Yang SW, Cha JM, Carlson K (2006) Anal Bioanal Chem 385:623–636

    Article  CAS  Google Scholar 

  28. Debremaeker D, Visky D, Chepkwony HK, Van Schepdeal A, Roets E, Hoogmartens J (2003) Rapid Commun Mass Spectrom 17:342–350

    Article  CAS  Google Scholar 

  29. Noguchi N, Emura A, Matsuyama H, O’Hara K, Sasatsu M, Kono M (1995) Antimicrobial Agents Chemother 39:2359–2363

    CAS  Google Scholar 

  30. Wright GD (2005) Adv Drug Deliv Rev 57:1451–1470

    Article  CAS  Google Scholar 

  31. Schlunzen F, Zarivach R, Harms J, Bashan A, Tocilj A, Albrecht R, Yonath A, Franceschi F (2001) Nature 413:814–821

    Article  CAS  Google Scholar 

  32. Robicsek A, Strahilevitz J, Jacoby GA, Macielag M, Abbanat D, Park CH, Bush K, Hooper DC (2006) Nature Med 12:83–88

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the Ministry of Science, Education and Sports of the Republic of Croatia through the project on organic contaminants as molecular markers of the anthropogenic impact on the environment (Project No: 098-0982934-2712). Technical assistance of Nenad Muhin is also gratefully acknowledged.

Author information

Authors and Affiliations

  1. Division of Marine and Environmental Research, Rudjer Boskovic Institute, 10000, Zagreb, Croatia

    Senka Terzic, Ivan Senta & Marijan Ahel

  2. Faculty of Food Technology and Biotechnology, University of Zagreb, 10000, Zagreb, Croatia

    Marin Matosic

Authors
  1. Senka Terzic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivan Senta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marin Matosic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marijan Ahel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marijan Ahel.

Electronic supplementary material

Below is the link to the electronic supplementary material.

(PDF 501 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Terzic, S., Senta, I., Matosic, M. et al. Identification of biotransformation products of macrolide and fluoroquinolone antimicrobials in membrane bioreactor treatment by ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Anal Bioanal Chem 401, 353–363 (2011). https://doi.org/10.1007/s00216-011-5060-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-011-5060-x

Keywords

Search

Navigation