Determination of Antimicrobial Residues in Honey by Liquid Chromatography Tandem Mass Spectrometry

  • Ádám Tölgyesi
  • Enikő Barta
  • Mary Sohn
  • Virender K. Sharma
Article
  • 5 Downloads

Abstract

Antibiotics are generally used worldwide against bacterial diseases in the treatment of food-producing animals. Since the residues of active agents or their metabolites can appear in these foods, the European Union, for instance, has set maximum residue limit concentrations for authorised veterinary drugs in foodstuffs. However, as yet, regulatory limits have not been established for honey and thus far, only recommendations exist. The aim of this study is to present a multiscreening method for residues in honey for the determination of 36 antimicrobial residues associated with several antibiotics of the B1 group (sulfonamides, trimethoprim, aminoglycosides, tetracyclines, quinolones and lincomycin) as well as the antibiotic griseofulvin. During the screening analysis, samples are hydrolysed in an acidified medium, purified on polymeric solid-phase extraction cartridges and subsequently analysed by reversed phase ion pair liquid chromatography tandem mass spectrometry. The liquid chromatographic separation was optimised by computer simulation with DryLab software. The positive identification of target compounds in suspicious samples was confirmed using earlier developed antibiotic class specific methods of which the aminoglycoside method is herein described in detail. The developed approaches were then applied to samples in the national monitoring program after their successful validation. Moreover, the screening and confirmatory methods were applied to proficiency test samples resulting in satisfactory identification and quantification. However, the analysis of real samples revealed that co-eluting target compounds can have considerable influence on the accuracy of this semi-quantitative multiscreening method.

Keywords

Antimicrobial residues Honey Liquid chromatography tandem mass spectrometry Screening Confirmation Proficiency test 

Notes

Acknowledgements

We wish to acknowledge the assist of Éva Pálffi, Tímea Kremniczky and Viktória Lipcsei in the sample preparations. Authors would like to thank Szabolcs Fekete for improving the paper.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics Approval

This article does not contain any studies with human or animal subjects performed by any of the authors.

Consent for Publication

Publication has been approved by all individual participants.

Informed Consent

Not applicable.

References

  1. AGRICULTURE AND RURAL DEVELOPMENT (2015) Beekeeping and honey - European Commission. Available from:https://ec.europa.eu/agriculture/honey_en
  2. Bargańska Ż, Namieśnik J, Ślebioda M (2011) Determination of antibiotic residues in honey. TrAC-Trend Anal Chem 30:1035–1041Google Scholar
  3. CRL Guidance Paper (2007) CRLs view on state of the art analytical methods for the national residue control plans. http://www.rivm.nl/bibliotheek/digitaaldepot/crlguidance2007.pdf
  4. CRL (2010) Guidelines for the validation of screening methods for residues of veterinary medicines (Initial validation and transfer). Community Reference Laboratories 20/1/2010. http://ec.europa.eu/food/food/chemicalsafety/residues/Guideline Validation Screening en.pdf Accessed 10 June 2017
  5. Commission Decision of 12 August 2002 implementing Council Directive 96/EC concerning the performance of analytical methods and the interpretation of results 2002/EC concerning the performance of analytical methods and the interpretation of results (2002/657/EC) (2002) Off J Eur Commun L221Google Scholar
  6. Commission Regulation (EU) No 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin (2010) Off J EU Legis L 15/1Google Scholar
  7. Fekete S, Fekete J, Molnár I, Ganzler K (2009) Rapid high performance liquid chromatography method development with high prediction accuracy, using 5cm long narrow bore columns packed with sub-2μm particles and Design Space computer modeling. J Chromatogr A 1216(45):7816–78EC concerning the performance of analytical methods and the interpretation of results 2002.  https://doi.org/10.1016/j.chroma.2009.09.043 CrossRefGoogle Scholar
  8. Forsgren E (2010) European foulbrood in honey bees. J Invertebr Pathol 103:S5–S9.  https://doi.org/10.1016/j.jip.2009.06.016 CrossRefGoogle Scholar
  9. Fyfe L, Okoro P, Paterson E, Coyle S, McDougall GJ (2017) Compositional analysis of Scottish honeys with antimicrobial activity against antibiotic-resistant bacteria reveals novel antimicrobial components. Food Sci Technol 79:52–59Google Scholar
  10. Galarini R, Saluti G, Giusepponi D, Rossi R, Moretti S (2015) Multiclass determination of 27 antibiotics in honey. Food Control 48:12–24CrossRefGoogle Scholar
  11. Gaugain-Juhel M, Delépine B, Gautier S, Fourmond MP, Gaudin V, Hurtaud-Pessel D, Verdon E, Sanders P (2009) Validation of a liquid chromatography-tandem mass spectrometry screening method to monitor 58 antibiotics in milk: a qualitative approach. Food Addit Contam 26(11):1459–1471.  https://doi.org/10.1080/02652030903150575 CrossRefGoogle Scholar
  12. Genersch E (2010) American foulbrood in honeybees and its causative agent, Paenibacillus larvae. J Invertebr Pathol 103:S10–S19.  https://doi.org/10.1016/j.jip.2009.06.015 CrossRefGoogle Scholar
  13. Hammel Y-A, Mohamed R, Gremaud E, LeBreton M-H, Guy PA (2008) Multi-screening approach to monitor and quantify 42 antibiotic residues in honey by liquid chromatography–tandem mass spectrometry. J Chromatogr A 1177(1):58–76.  https://doi.org/10.1016/j.chroma.2007.10.112 CrossRefGoogle Scholar
  14. Hawari KE, Mokh S, Doumyati S, Iskandarani MA, Verdon E (2017) Development and validation of a multiclass method for the determination of antibiotic residues in honey using liquid chromatography-tandem mass spectrometry. Food Addit Contam Part A 34(4):582–597.  https://doi.org/10.1080/19440049.2016.1EC concerning the performance of analytical methods and the interpretation of results 20022491
  15. JECFA (2013) Joint FAO/WHO Expert Committee On Food Additives. Seventy-eighth meeting (Residues of veterinary drugs); 2013 Nov 5–14; Geneva. Available from: http://www.fao.org/fileadmin/templates/agns/pdf/jecfa/JECFA_78_Summary_report_Version_final.pdf
  16. Jin Y, Zhang J, Zhao W, Zhang W, Wang L, Zhou J, Li Y (2017) Development and validation of a multiclass method for the quantification of veterinary drug residues in honey and royal jelly by liquid chromatography–tandem mass spectrometry. Food Chem 221:1298–1307CrossRefGoogle Scholar
  17. Kaufmann A, Butcher P, Maden K, Walker S, Widmer M (2011) Development of an improved high resolution mass spectrometry based multi-residue method for veterinary drugs in various food matrices. Anal Chim Acta 700:86–94CrossRefGoogle Scholar
  18. Kaufmann A, Butcher P, Maden K (2012) Determination of aminoglycoside residues by liquid chromatography and tandem mass spectrometry in a variety of matrices. Anal Chim Acta 711:46–53CrossRefGoogle Scholar
  19. Kivrak I, Kivrak S, Harmandar M (2016) Development of a rapid method for the determination of antibiotic residues in honey using UPLC-ESI-MS/MS.. Food Sci Technol (Campinas) vol. 36 online version Available from:  https://doi.org/10.1590/1678-457X.0037
  20. Kujawski MW, Namieśnik J (2008) Challenges in preparing honey samples for chromatographic determination of contaminants and trace residues. TrAC-Trend Anal Chem 27(9):785–793.  https://doi.org/10.1016/j.trac.2008.07.004 CrossRefGoogle Scholar
  21. Lafontaine C, Shi Y, Espourteille FA (2009) Multi-class antibiotic screening of honey using Online Extraction with LC-MS/MS. Thermo Scientific application note: 464. Available from: https://tools.thermofisher.com/content/sfs/brochures/AN464-multi-class-antibiotic-screening-of-honey-using-online-extraction-with-lc-msms.pdf
  22. Lopez MI, Pettis JS, Barton Smith I, Chu P-S (2008) Multiclass determination and confirmation of antibiotic residues in honey using LC-MS/MS. J Agric Food Chem 56(5):1553–1559.  https://doi.org/10.1021/jf073EC concerning the performance of analytical methods and the interpretation of results 20026w
  23. Louppis AP, Kontominas MG, Papastephanou C (2017) Determination of antibiotic residues in honey by high-performance liquid chromatography with electronspray ionization tandem mass spectrometry. Food Anal Methods In press 10(10):3385–3397.  https://doi.org/10.1007/s12161-017-0899-x CrossRefGoogle Scholar
  24. Núñez O, Moyano E, Galceran MT (2005) LC–MS/MS analysis of organic toxics in food. TrAC 24:683–703Google Scholar
  25. Orso D, Floriano L, Ribeiro LC, Bandeira NMG, Prestes OD, Zanella R (2016) Simultaneous determination of multiclass pesticides and antibiotics in honey samples based on ultra-high performance liquid chromatography-tandem mass spectrometry. Food Anal Methods 9(6):1638–1653.  https://doi.org/10.1007/s12161-015-0339-8 CrossRefGoogle Scholar
  26. Shendy AH, Al-Ghobashy MA, Gad Alla SA, Lotfy HM (2016) Development and validation of a modified QuEChERS protocol coupled to LC–MS/MS for simultaneous determination of multi-class antibiotic residues in honey. Food Chem 190:982–989CrossRefGoogle Scholar
  27. Spaggiari D, Mehl F, Desfontaine V, Perrenoud AGG, Fekete S, Rudaz S, Guillarme D (2014) Comparison of liquid chromatography and supercritical fluid chromatography coupled to compact single quadrupole mass spectrometer for targeted in vitro metabolism assay. J Chromatogr A 1371:244–256.  https://doi.org/10.1016/j.chroma.2014.10.055 CrossRefGoogle Scholar
  28. Spörri AS, Jan P, Cognard E, Ortelli D, Edder P (2014) Comprehensive screening of veterinary drugs in honey by ultra-high-performance liquid chromatography coupled to mass spectrometry. Food Addit Contam Part A 31(5):806–816.  https://doi.org/10.1080/19440049.2014.891295 CrossRefGoogle Scholar
  29. Tian YF, Chen GH, Guo LH, Guo X, Mei X-Y (2015) Methodology studies on detection of aminoglycoside residues. Food Anal Met 8(7):1842–1857.  https://doi.org/10.1007/s12161-014-0067-5 CrossRefGoogle Scholar
  30. Thompson TS, van den Heever JP (2012) Degradation of erythromycin in honey and selection of suitable marker residues for food safety analysis. Food Chem 133(4):1510–1520.  https://doi.org/10.1016/j.foodchem.2012.02.041 CrossRefGoogle Scholar
  31. Thompson TS, Pernal SF, Noot DK, Melathopoulos AP, van den Heever JP (2007) Degradation of incurred tylosin to desmycosin—implications for residue analysis of honey. Anal Chim Acta 586(1-2):304–311.  https://doi.org/10.1016/j.aca.2006.09.043 CrossRefGoogle Scholar
  32. Tölgyesi Á, Berky R, Békési K, Fekete S, Fekete J, Sharma VK (2013) Quantitative analysis of sulfonamide residues in real honey using high performance liquid chromatography with fluorescence and tandem mass spectrometric detection. J Liq Chromatogr Rel Tech 36:1105–1125Google Scholar
  33. Tölgyesi Á, Fekete S, Békési K, Tóth E, Sharma VK, Fekete J (2012) Fast analysis of lincomycin in honey, muscle, milk, and egg using liquid chromatography-tandem mass spectrometry. J Chromatogr Sci 50(3):190–198.  https://doi.org/10.1093/chromsci/bmr046 CrossRefGoogle Scholar
  34. Tölgyesi Á, Tölgyesi L, Békési K, Sharma VK, Fekete J (2014) Determination of tetracyclines in pig and other meat samples using liquid chromatography coupled with diode array and tandem mass spectrometric detectors. Meat Sci 96(3):1332–1339.  https://doi.org/10.1016/j.meatsci.2013.11.011 CrossRefGoogle Scholar
  35. Zhu Z, Liu G, Wang F, Sasanya JJ, Cannavan A (2016) Development of a liquid chromatography tandem mass spectrometric method for simultaneous determination of 15 aminoglycoside residues in porcine tissues. Food Anal Met 9(9):2587–2599.  https://doi.org/10.1007/s12161-016-0446-1 CrossRefGoogle Scholar
  36. Zhu WX, Yang JZ, Wei W, Liu YF, Zhang SS (2008) Simultaneous determination of 13 aminoglycoside residues in foods of animal origin by liquid chromatography-electrospray ionization tandem mass spectrometry with two consecutive solid-phase extraction steps. J Chromatogr A 1207(1–2):29–37.  https://doi.org/10.1016/j.chroma.2008.08.033 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.National Food Chain Safety Office, Food and Feed Safety DirectorateFood Toxicological National Reference LaboratoryBudapestHungary
  2. 2.Department of Inorganic and Analytical ChemistryBudapest University of Technology and EconomicsBudapestHungary
  3. 3.Department of Chemistry, Florida Institute of Technology150 West University BoulevardMelbourneUSA
  4. 4.Department of Environmental and Occupational HealthSchool of Public Health, Texas A&M UniversityCollege StationUSA

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