Skip to main content
SpringerLink
Log in

Simultaneous determination of multiclass antibiotics and their metabolites in four types of field-grown vegetables

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

Abstract

The developed method was evaluated for the determination of 10 antibiotics belonging to four chemical classes (fluoroquinolones, sulfonamides, lincosamides, and metoxybenzylpyrimidines) and six of their metabolites in four vegetable matrices (lettuce, tomato, cauliflower, and broad beans). The reported method detection limits were sufficiently low (0.1–5.8 ng/g dry weight) to detect target compounds in vegetables under real agricultural practices. Absolute and relative recovery values ranged from 40 to 118% and from 70 to 118%, respectively, for all targeted compounds at the spike level of 100 ng/g dry weight. Regarding method precision, the highest relative standard deviation (RSD) was obtained for enrofloxacin in lettuce (20%), while for the rest of the compounds in all matrices, the RSD values were below 20% for the same spike level. Matrix effects, due to electrospray ionization, ranged from − 26 to 29% for 85% of all estimated values. In a field study, four of the 10 targeted antibiotics were detected in tested vegetables. For the first time, antibiotic metabolites were quantified in vegetables grown under real field conditions. More specifically, decarboxyl ofloxacin and TMP304 were detected in tomato fruits (1.5 ng/g dry weight) and lettuce leaves (21.0–23.1 ng/g dry weight), respectively. It is important to remark that the concentration of TMP304 was five times higher than that from the parental compound, emphasizing the importance of metabolite analysis in monitoring studies. Therefore, the method provided a robust, reliable, and simple-to-use tool that could prove useful for routine multiclass analysis of antibiotics and their metabolites in vegetable samples.

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

Similar content being viewed by others

References

  1. Yilmaz C, Özcengiz G. Antibiotics : pharmacokinetics , toxicity , resistance and multidrug efflux pumps. Biochem Pharmacol. 2016;133:43–62. https://doi.org/10.1016/j.bcp.2016.10.005.

    Article  CAS  PubMed  Google Scholar 

  2. Christou A, Agüera A, Bayona JM, Cytryn E, Manaia CM, Michael C, et al. The potential implications of reclaimed wastewater reuse for irrigation on the agricultural environment : the knowns and unknowns of the fate of antibiotics and antibiotic resistant bacteria and resistance genes - a review. Water Res. 2017;123:448–67. https://doi.org/10.1016/j.watres.2017.07.004.

    Article  CAS  PubMed  Google Scholar 

  3. Hu F, Bian K, Liu Y, Su Y, Zhou T, Song X, et al. Development of a modified QUick , Easy , CHeap , Effective, Rugged and Safe method for the determination of multi-class antimicrobials in vegetables by liquid chromatography tandem mass spectrometry. J Chromatogr A. 2014;1368:52–63. https://doi.org/10.1016/j.chroma.2014.09.074.

    Article  CAS  PubMed  Google Scholar 

  4. Grossberger A, Hadar Y, Borch T, Chefetz B. Biodegradability of pharmaceutical compounds in agricultural soils irrigated with treated wastewater. Environ Pollut. 2014;185:168–77. https://doi.org/10.1016/j.envpol.2013.10.038.

    Article  CAS  PubMed  Google Scholar 

  5. Sharma VK, Johnson N, Cizmas L, McDonald TJ, Kim H. A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes. Chemosphere. 2016;150:702–14. https://doi.org/10.1016/j.chemosphere.2015.12.084.

    Article  CAS  PubMed  Google Scholar 

  6. Tasho RP, Cho JY. Veterinary antibiotics in animal waste, its distribution in soil and uptake by plants : a review. Sci Total Environ. 2016;563–564:366–76. https://doi.org/10.1016/j.scitotenv.2016.04.140.

    Article  CAS  PubMed  Google Scholar 

  7. Pan M, Chu LM. Fate of antibiotics in soil and their uptake by edible crops. Sci Total Environ. 2017;599–600:500–12. https://doi.org/10.1016/j.scitotenv.2017.04.214.

    Article  CAS  PubMed  Google Scholar 

  8. Salvia MV, Vulliet E, Wiest L, Baudot R, Cren-Olivé C. Development of a multi-residue method using acetonitrile-based extraction followed by liquid chromatography-tandem mass spectrometry for the analysis of steroids and veterinary and human drugs at trace levels in soil. J Chromatogr A. 2012;1245:122–33. https://doi.org/10.1016/j.chroma.2012.05.034.

    Article  CAS  PubMed  Google Scholar 

  9. Yang S, Carlson KH. Solid-phase extraction – high-performance liquid chromatography – ion trap mass spectrometry for analysis of trace concentrations of macrolide antibiotics in natural and waste water matrices. J Chromatogr A. 2004;1038:141–55. https://doi.org/10.1016/j.chroma.2004.02.084.

    Article  CAS  PubMed  Google Scholar 

  10. Azanu D, Mortey C, Darko G, Weisser JJ, Styrishave B, Abaidoo RC. Uptake of antibiotics from irrigation water by plants. Chemosphere. 2016;157:107–14. https://doi.org/10.1016/j.chemosphere.2016.05.035.

    Article  CAS  PubMed  Google Scholar 

  11. Gullberg E, Cao S, Berg OG, Ilback K, Sandegren L, Hughes D, et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 2011;7:1–9. https://doi.org/10.1371/journal.ppat.1002158.

    Article  CAS  Google Scholar 

  12. Van Den MT, Van PE, Van PC, Herman L, Heyndrickx M, Rasschaert G, et al. Development , validation and application of an ultra high performance liquid chromatographic-tandem mass spectrometric method for the simultaneous detection and quantification of five different classes of veterinary antibiotics in swine manure. J Chromatogr A. 2016;1429:248–57. https://doi.org/10.1016/j.chroma.2015.12.046.

    Article  CAS  Google Scholar 

  13. Sarmah AK, Meyer MT, Boxall ABA. A global perspective on the use, sale, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere. 2006;65:725–59. https://doi.org/10.1016/j.chemosphere.2006.03.026.

    Article  CAS  PubMed  Google Scholar 

  14. Goldstein M, Shenker M, Chefetz B. Insights into the uptake processes of wastewater-borne pharmaceuticals by vegetables. Environ Sci Technol. 2014;48:5593–600. https://doi.org/10.1021/es5008615.

    Article  CAS  PubMed  Google Scholar 

  15. Yu X, Liu H, Pu C, Chen J, Sun Y, Hu L. Determination of multiple antibiotics in leafy vegetables using QuEChERS–UHPLC–MS/MS. J Sep Sci. 2018;41:713–22. https://doi.org/10.1002/jssc.201700798.

    Article  CAS  PubMed  Google Scholar 

  16. He Z, Wang Y, Xu Y, Liu X. Determination of antibiotics in vegetables using QuEChERS-based method and liquid chromatography-quadrupole linear ion trap mass spectrometry. Food Anal Methods. 2018;11:2857–64. https://doi.org/10.1007/s12161-018-1252-8.

    Article  Google Scholar 

  17. Hurtado C, Domínguez C, Pérez-Babace L, Cañameras N, Comas J, Bayona JM. Estimate of uptake and translocation of emerging organic contaminants from irrigation water concentration in lettuce grown under controlled conditions. J Hazard Mater. 2016;305:139–48. https://doi.org/10.1016/j.jhazmat.2015.11.039.

    Article  CAS  PubMed  Google Scholar 

  18. Malchi T, Maor Y, Tadmor G, Shenker M, Chefetz B. Irrigation of root vegetables with treated wastewater: evaluating uptake of pharmaceuticals and the associated human health risks. Environ Sci Technol. 2014;48:9325–33. https://doi.org/10.1021/es5017894.

    Article  CAS  PubMed  Google Scholar 

  19. Christou A, Karaolia P, Hapeshi E, Michael C, Fatta-Kassinos D. Long-term wastewater irrigation of vegetables in real agricultural systems: concentration of pharmaceuticals in soil, uptake and bioaccumulation in tomato fruits and human health risk assessment. Water Res. 2017;109:24–34. https://doi.org/10.1016/j.watres.2016.11.033.

    Article  CAS  PubMed  Google Scholar 

  20. Hawker DW, Cropp R, Boonsaner M. Uptake of zwitterionic antibiotics by rice (Oryza sativa L.) in contaminated soil. J Hazard Mater. 2013;263:458–66. https://doi.org/10.1016/j.jhazmat.2013.09.066.

    Article  CAS  PubMed  Google Scholar 

  21. Marsoni M, De Mattia F, Labra M, Bruno A, Bracale M, Vannini C. Uptake and effects of a mixture of widely used therapeutic drugs in Eruca sativa L. and Zea mays L. plants. Ecotoxicol Environ Saf. 2014;108:52–7. https://doi.org/10.1016/j.ecoenv.2014.05.029.

    Article  CAS  PubMed  Google Scholar 

  22. Riemenschneider C, Al-Raggad M, Moeder M, Seiwert B, Salameh E, Reemtsma T. Pharmaceuticals, their metabolites, and other polar pollutants in field-grown vegetables irrigated with treated municipal wastewater. J Agric Food Chem. 2016;64:5784–92. https://doi.org/10.1021/acs.jafc.6b01696.

    Article  CAS  PubMed  Google Scholar 

  23. Wu X, Conkle JL, Ernst F, Gan J. Treated wastewater irrigation : uptake of pharmaceutical and personal care products by common vegetables under field conditions. Environ Sci Technol. 2014;48:11286–93. https://doi.org/10.1021/es502868k.

    Article  CAS  PubMed  Google Scholar 

  24. Franklin AM, Williams CF, Andrews DM, Woodward EE, Watson JE. Uptake of three antibiotics and an antiepileptic drug by wheat crops spray irrigated with wastewater treatment plant effluent. J Environ Qual. 2016;45:546–54. https://doi.org/10.2134/jeq2015.05.0257.

    Article  CAS  PubMed  Google Scholar 

  25. Liu X, Caleb J, Meng X. Usage , residue , and human health risk of antibiotics in Chinese aquaculture: a review. Environ Pollut. 2017;223:161–9. https://doi.org/10.1016/j.envpol.2017.01.003.

    Article  CAS  PubMed  Google Scholar 

  26. Majewsky M, Wagner D, Delay M, Bra S, Yargeau V, Horn H. Antibacterial activity of sulfamethoxazole transformation products (TPs ): general relevance for sulfonamide TPs modified at the para position. Chem Res Toxicol. 2014;27:1821–8. https://doi.org/10.1021/tx500267x.

    Article  CAS  PubMed  Google Scholar 

  27. Cvancarova M, Moeder M, Filipova A, Cajthaml T. Biotransformation of fluoroquinolone antibiotics by ligninolytic fungi - metabolites, enzymes and residual antibacterial activity. Chemosphere. 2015;136:311–20. https://doi.org/10.1016/j.chemosphere.2014.12.012.

    Article  CAS  PubMed  Google Scholar 

  28. García-Galán MJ, Díaz-Cruz S, Barceló D. Multiresidue trace analysis of sulfonamide antibiotics and their metabolites in soils and sewage sludge by pressurized liquid extraction followed by liquid chromatography-electrospray-quadrupole linear ion trap mass spectrometry. J Chromatogr A. 2013;1275:32–40. https://doi.org/10.1016/j.chroma.2012.12.004.

    Article  CAS  PubMed  Google Scholar 

  29. Wang J, Gardinali PR. Identification of phase II pharmaceutical metabolites in reclaimed water using high resolution benchtop Orbitrap mass spectrometry. Chemosphere. 2014;107:65–73. https://doi.org/10.1016/j.chemosphere.2014.03.021.

    Article  CAS  PubMed  Google Scholar 

  30. Dudley S, Sun C, Jiang J, Gan J. Metabolism of sulfamethoxazole in Arabidopsis thaliana cells and cucumber seedlings. Environ Pollut. 2018;242:1748–57. https://doi.org/10.1016/j.envpol.2018.07.094.

    Article  CAS  PubMed  Google Scholar 

  31. Jewell KS, Castronovo S, Wick A, Falås P, Joss A, Ternes TA. New insights into the transformation of trimethoprim during biological wastewater treatment. Water Res. 2016;88:550–7. https://doi.org/10.1016/j.watres.2015.10.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pan M, Wong CKC, Chu LM. Distribution of antibiotics in wastewater-irrigated soils and their accumulation in vegetable crops in the Pearl River Delta, southern China. J Agric Food Chem. 2014;62:11062–9. https://doi.org/10.1021/jf503850v.

    Article  CAS  PubMed  Google Scholar 

  33. Wu X, Ernst F, Conkle JL, Gan J. Comparative uptake and translocation of pharmaceutical and personal care products (PPCPs) by common vegetables. Environ Int. 2013;60:15–22. https://doi.org/10.1016/j.envint.2013.07.015.

    Article  CAS  PubMed  Google Scholar 

  34. Jones-Lepp TL, Sanchez CA, Moy T, Kazemi R. Method development and application to determine potential plant uptake of antibiotics and other drugs in irrigated crop production systems. J Agric Food Chem. 2010;58:11568–73. https://doi.org/10.1021/jf1028152.

    Article  CAS  PubMed  Google Scholar 

  35. Wu X, Conkle JL, Gan J. Multi-residue determination of pharmaceutical and personal care products in vegetables. J Chromatogr A. 2012;1254:78–86. https://doi.org/10.1016/j.chroma.2012.07.041.

    Article  CAS  PubMed  Google Scholar 

  36. Chitescu CL, Oosterink E, De Jong J, Stolker AAM. Ultrasonic or accelerated solvent extraction followed by U-HPLC-high mass accuracy MS for screening of pharmaceuticals and fungicides in soil and plant samples. Talanta. 2012;88:653–62. https://doi.org/10.1016/j.talanta.2011.11.054.

    Article  CAS  PubMed  Google Scholar 

  37. Gmurek M, Horn H, Majewsky M. Phototransformation of sulfamethoxazole under simulated sunlight: transformation products and their antibacterial activity toward Vibrio fischeri. Sci Total Environ. 2015;538:58–63. https://doi.org/10.1016/j.scitotenv.2015.08.014.

    Article  CAS  PubMed  Google Scholar 

  38. Barcellos R, Mara T, Ruaro C, Díaz-Cruz MS, Barceló D. Determination of sulfonamide antibiotics and metabolites in liver , muscle and kidney samples by pressurized liquid extraction or ultrasound-assisted extraction followed by liquid chromatography – quadrupole linear ion trap-tandem mass spectrometry (HPLC). Talanta. 2015;134:768–78. https://doi.org/10.1016/j.talanta.2014.10.045.

    Article  CAS  Google Scholar 

  39. Serra-Compte A, Álvarez-Muñoz D, Rodríguez-Mozaz S, Barceló D. Multi-residue method for the determination of antibiotics and some of their metabolites in seafood. Food Chem Toxicol. 2017;104:3–13. https://doi.org/10.1016/j.fct.2016.11.031.

    Article  CAS  PubMed  Google Scholar 

  40. Margenat A, Matamoros V, Díez S, Cañameras N, Comas J, Bayona JM. Occurrence of chemical contaminants in peri-urban agricultural irrigation waters and assessment of their phytotoxicity and crop productivity. Sci Total Environ. 2017;599–600:1140–8. https://doi.org/10.1016/j.scitotenv.2017.05.025.

    Article  CAS  PubMed  Google Scholar 

  41. Paíga P, Santos LHMLM, Delerue-Matos C. Development of a multi-residue method for the determination of human and veterinary pharmaceuticals and some of their metabolites in aqueous environmental matrices by SPE-UHPLC–MS/MS. J Pharm Biomed Anal. 2017;135:75–86. https://doi.org/10.1016/j.jpba.2016.12.013.

    Article  CAS  PubMed  Google Scholar 

  42. Zhang Z, Cheng H. Recent development in sample preparation and analytical techniques for determination of quinolone residues in food products. Crit Rev Anal Chem. 2017;47:223–50. https://doi.org/10.1080/10408347.2016.1266924.

    Article  CAS  PubMed  Google Scholar 

  43. Díaz-Alvarez M, Turiel E, Martín-Esteban A. Selective sample preparation for the analysis of (fluoro)quinolones in baby food: molecularly imprinted polymers versus anion-exchange resins. Anal Bioanal Chem. 2008;393:899–905. https://doi.org/10.1007/s00216-008-2300-9.

    Article  CAS  PubMed  Google Scholar 

  44. Priego-Capote F, Luque de Castro MD. Ultrasound-assisted digestion: a useful alternative in sample preparation. J Biochem Biophys Methods. 2007;70:299–310. https://doi.org/10.1016/j.jbbm.2006.09.006.

    Article  CAS  PubMed  Google Scholar 

  45. Huber C, Bartha B, Schröder P. Metabolism of diclofenac in plants – hydroxylation is followed by glucose conjugation. J Hazard Mater. 2012;243:250–6. https://doi.org/10.1016/j.jhazmat.2012.10.023.

    Article  CAS  PubMed  Google Scholar 

  46. Fernandez-Torres R, Bello Lopez MA, Olias Consentino M, Callejon Mochon M, Ramos Payan M. Enzymatic-microwave assisted extraction and high-performance liquid chromatography-mass spectrometry for the determination of selected veterinary antibiotics in fish and mussel samples. J Pharm Biomed Anal. 2011;54:1146–56. https://doi.org/10.1016/j.jpba.2010.12.002.

    Article  CAS  PubMed  Google Scholar 

  47. Ji K, Kho Y, Park C, Paek D, Ryu P, Paek D, et al. Influence of water and food consumption on inadvertent antibiotics intake among general population. Environ Res. 2010;110:641–9. https://doi.org/10.1016/j.envres.2010.06.008.

    Article  CAS  PubMed  Google Scholar 

  48. Zhou JL, Maskaoui K, Lufadeju A. Optimization of antibiotic analysis in water by solid-phase extraction and high performance liquid chromatography-mass spectrometry/mass spectrometry. Anal Chim Acta. 2012;731:32–9. https://doi.org/10.1016/j.aca.2012.04.021.

    Article  CAS  PubMed  Google Scholar 

  49. Gao P, Ding Y, Li H, Xagoraraki I. Occurrence of pharmaceuticals in a municipal wastewater treatment plant: mass balance and removal processes. Chemosphere. 2012;88:17–24. https://doi.org/10.1016/j.chemosphere.2012.02.017.

    Article  CAS  PubMed  Google Scholar 

  50. Ribeiro AR, Pedrosa M, Moreira NFF, Pereira MFR, Silva AMT. Environmental friendly method for urban wastewater monitoring of micropollutants defined in the Directive 2013 / 39 / EU and Decision 2015 / 495 / EU. J Chromatogr A. 2015;1418:140–9. https://doi.org/10.1016/j.chroma.2015.09.057.

    Article  CAS  PubMed  Google Scholar 

  51. Riemenschneider C, Seiwert B, Goldstein M, Al-Raggad M, Salameh E, Chefetz B, et al. An LC-MS/MS method for the determination of 28 polar environmental contaminants and metabolites in vegetables irrigated with treated municipal wastewater. Anal Methods. 2017;9:1273–81. https://doi.org/10.1039/C6AY02984A.

    Article  CAS  Google Scholar 

  52. Li XW, Xie YF, Li CL, Zhao HN, Zhao H, Wang N, et al. Investigation of residual fluoroquinolones in a soil-vegetable system in an intensive vegetable cultivation area in northern China. Sci Total Environ. 2013;468–469:258–64. https://doi.org/10.1016/j.scitotenv.2013.08.057.

    Article  CAS  PubMed  Google Scholar 

  53. Holmes P, Boxall A, Johnson P, James K, Assem L, Levy L. Evaluation of the potential risks to consumers from indirect exposure to veterinary medicines FINAL REPORT: Inst Environ Heal Cranf Univ; 2007.

  54. Sallach JB, Snow D, Hodges L, Li X, Bartelt-Hunt S. Development and comparison of four methods for the extraction of antibiotics from a vegetative matrix. Environ Toxicol Chem. 2016;35:889–97. https://doi.org/10.1002/etc.3214.

    Article  CAS  PubMed  Google Scholar 

  55. Hussain S, Naeem M, Chaudhry MN, Iqbal MA. Accumulation of residual antibiotics in the vegetables irrigated by pharmaceutical wastewater. Expo Heal. 2015;8:107–15. https://doi.org/10.1007/s12403-015-0186-2.

    Article  CAS  Google Scholar 

  56. Hu X, Zhou Q, Luo Y. Occurrence and source analysis of typical veterinary antibiotics in manure, soil, vegetables and groundwater from organic vegetable bases, northern China. Environ Pollut. 2010;158:2992–8. https://doi.org/10.1016/j.envpol.2010.05.023.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work presented in this paper is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 675530. The authors also gratefully acknowledge the financial support of the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) through Project AGL2014-59353-R.

Funding

This study was funded by H2020 MSCA grant agreement 675530 and the MEIC project nr. AGL2014-59353-R.

Author information

Authors and Affiliations

  1. Institute of Environmental Assessment and Water Research, Department of Environmental Chemistry, Spanish National Research Council (IDAEA-CSIC), C. Jordi Girona 18-26, 08034, Barcelona, Spain

    Đorđe Tadić, Víctor Matamoros & Josep M. Bayona

Authors
  1. Đorđe Tadić
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Víctor Matamoros
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Josep M. Bayona
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Josep M. Bayona.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Disclaimer

The content of this article reflects only the authors’ views, and the Research Executive Agency is not responsible for any use that may be made of the information it contains.

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 79 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tadić, Đ., Matamoros, V. & Bayona, J.M. Simultaneous determination of multiclass antibiotics and their metabolites in four types of field-grown vegetables. Anal Bioanal Chem 411, 5209–5222 (2019). https://doi.org/10.1007/s00216-019-01895-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-019-01895-y

Keywords

Search

Navigation