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Determination of non-steroidal anti-inflammatory drugs and their metabolites in milk by liquid chromatography–tandem mass spectrometry

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Abstract

Non-steroidal anti-inflammatory drugs are widely used for treatment of animals. According to Council Directive 96/23/EC, residues of these drugs must be monitored because of the potential risk they pose to the consumers’ health. For this reason an LC–MS–MS method was developed for detection of wide range of NSAIDs, including both “acidic” NSAIDs (carprofen, diclofenac, flunixin, meloxicam, phenylbutazone, oxyphenbutazone, tolfenamic acid, mefenamic acid, naproxen, ketoprofen, ibuprofen, firocoxib, rofecoxib, and celecoxib) and “basic” NSAIDs (four metamizole metabolites). Analytes were extracted from milk samples with acetonitrile in the presence of ammonium acetate. One portion of the extract was directly analyzed for the presence of metamizole metabolites; a second portion was cleaned with an amino cartridge. All NSAIDs were separated on a Phenomenex Luna C8(2) column and analyzed by LC–MS–MS in negative (acidic NSAIDs) and positive (metamizole metabolites) ion modes. The method was validated in accordance with the requirements of Commission Decision 2002/657/EC. Within-laboratory reproducibility was in the range 7–28%, and accuracy was in the range 71–116%. The method enabled detection of all the analytes with the expected sensitivity, below the recommended concentrations. The method fulfills the criteria for confirmatory methods and, because of its efficiency, may also be used for screening purposes. The procedure was also successfully verified in the proficiency test organized by EU-RL in 2010. As far as the authors are aware, this is one of the first methods capable of detecting diclofenac residues below the MRL in milk (0.1 μg kg−1). An additional advantage is the possibility of simultaneous determination of “acidic” NSAIDs and metamizole metabolites.

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References

  1. Commission Regulation 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin. Off J Eur Union L15:1–71

  2. Council Directive 96/23/EC of 29 April 1996 on measures to monitor certain substances and residues thereof in live animals and animal products and repealing Directives 85/ 358/EEC and 86/469/EEC and Decisions 89/187/EEC and 91/664/EEC. Off J Eur Commun. L125

  3. Gallo P, Fabbrocino S, Vinci F, Fiori M, Danese V, Serpe L (2008) Confirmatory identification of sixteen non-steroidal anti-inflammatory drug residues in raw milk by liquid chromatography coupled with ion trap mass spectrometry. Rapid Commun Mass Spectrom 22:841–54

    Article  CAS  Google Scholar 

  4. Gallo P, Fabbrocino S, Dowling G, Salini M, Fiori M, Perretta G, Serpe L (2010) Confirmatory analysis of non-steroidal anti-inflammatory drugs in bovine milk by high-performance liquid chromatography with fluorescence detection. J Chromatogr A 1217:2832–9

    Article  CAS  Google Scholar 

  5. Dowling G, Gallo P, Malone E, Regan L (2009) Rapid confirmatory analysis of non-steroidal anti-inflammatory drugs in bovine milk by rapid resolution liquid chromatography tandem mass spectrometry. J Chromatogr A 1216:8117–31

    Article  CAS  Google Scholar 

  6. Malone EM, Dowling G, Elliott CT, Kennedy DG, Regan L (2009) Development of a rapid, multi-class method for the confirmatory analysis of anti-inflammatory drugs in bovine milk using liquid chromatography tandem mass spectrometry. J Chromatogr A 1216:8132–40

    Article  CAS  Google Scholar 

  7. Dowling G, Malone E, Harbison T, Martin S (2010) Analytical strategy for the determination of non-steroidal anti-inflammatory drugs in plasma and improved analytical strategy for the determination of authorized and non-authorized non-steroidal anti-inflammatory drugs in milk by LC–MS–MS. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 27:962–82

    CAS  Google Scholar 

  8. Dubreil-Chéneau E, Pirotais Y, Bessiral M, Roudaut B, Verdon E (2011) Development and validation of a confirmatory method for the determination of 12 non-steroidal anti-inflammatory drugs in milk using liquid chromatography-tandem mass spectrometry. J Chromatogr A 1218:6292–301

    Article  Google Scholar 

  9. Stolker AA, Rutgers P, Oosterink E, Lasaroms JJ, Peters RJ, van Rhijn JA, Nielen MW (2008) Comprehensive screening and quantification of veterinary drugs in milk using UPLC–ToF-MS. Anal Bioanal Chem 391:2309–22

    Article  CAS  Google Scholar 

  10. Dowling G, Gallo P, Fabbrocino S, Serpe L, Regan L (2008) Determination of ibuprofen, ketoprofen, diclofenac and phenylbutazone in bovine milk by gas chromatography–tandem mass spectrometry. Food AdditContam Part A Chem Anal Control Expo Risk Assess 25:1497–508

    CAS  Google Scholar 

  11. Arroyo D, Ortiz MC, Sarabia LA (2011) Optimization of the derivatization reaction and the solid-phase microextraction conditions using a D-optimal design and three-way calibration in the determination of non-steroidal anti-inflammatory drugs in bovine milk by gas chromatography-mass spectrometry. J Chromatogr A 1218:4487–97

    Article  CAS  Google Scholar 

  12. Azzouz A, Jurado-Sánchez B, Souhail B, Ballesteros E (2011) Simultaneous determination of 20 pharmacologically active substances in cow’s milk, goat’s milk, and human breast milk by gas chromatography–mass spectrometry. J Agric Food Chem 59:5125–5132

    Article  CAS  Google Scholar 

  13. Commission Decision of 12 August 2002 implementing Council Directive 96/23/EC concerning the performance of analytical methods and the interpretation of results (2002/657/EC). Off J Eur Commun L221:8–3

  14. Dowling G, Gallo P, Regan L (2009) Confirmatory analysis of firocoxib in bovine milk by rapid resolution liquid chromatography tandem mass spectrometry. J Chromatogr B 877:541–546

    Article  CAS  Google Scholar 

  15. Starek M (2011) Review of the applications of different analytical techniques for coxibs research. Talanta 85:8–27

    Article  CAS  Google Scholar 

  16. Taylor PJ (2005) Matrix effects: The Achilles heel of quantitative high-performance liquid chromatography–electrospray–tandem mass spectrometry. Clin Biochem 38:328

    Article  CAS  Google Scholar 

  17. CRL Guidance Paper (7 December 2007) CRLs view on state of the art analytical methods for national residue control plans

  18. Jedziniak P, Szprengier-Juszkiewicz T, Olejnik M, Żmudzki J (2010) Detemination of non-steroidal anti-inflammatory drugs residues in animal muscles by liquid chromatography – tandem mass spectrometry. Anal Chim Acta 672:85–92

    Article  CAS  Google Scholar 

  19. Jedziniak P, Szprengier-Juszkiewicz T, Olejnik M (2009) Multi-residue screening method for determination of non-steroidal anti-inflammatory drugs residues in cow milk with HPLC–UV and its application to meloxicam residue depletion study. Bull Vet Inst Pulawy 53:731–739

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100, Puławy, Poland

    Piotr Jedziniak, Teresa Szprengier-Juszkiewicz, Konrad Pietruk, Edyta Śledzińska & Jan Żmudzki

Authors
  1. Piotr Jedziniak
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  2. Teresa Szprengier-Juszkiewicz
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  3. Konrad Pietruk
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  4. Edyta Śledzińska
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  5. Jan Żmudzki
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Correspondence to Piotr Jedziniak.

Additional information

Published in the special paper collection Recent Advances in Food Analysis with guest editors J. Hajslova, R. Krska, M. Nielen.

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Jedziniak, P., Szprengier-Juszkiewicz, T., Pietruk, K. et al. Determination of non-steroidal anti-inflammatory drugs and their metabolites in milk by liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 403, 2955–2963 (2012). https://doi.org/10.1007/s00216-012-5860-7

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  • DOI: https://doi.org/10.1007/s00216-012-5860-7

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