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Optimization and validation of a hydrophilic interaction liquid chromatography–tandem mass spectrometry method for the determination of 13 top-prescribed pharmaceuticals in influent wastewater

Analytical and Bioanalytical Chemistry volume 398, pages 2211–2222 (2010)Cite this article

Abstract

A sensitive hydrophilic interaction liquid chromatography (HILIC)–tandem mass spectrometry method was developed and validated for the analysis of 13 pharmaceuticals (omeprazole, pantoprazole, ranitidine, citalopram, fluoxetine, paroxetine, venlafaxine, tramadol, nebivolol, metoprolol, atenolol, bisoprolol and metformin) in influent wastewater. The analytes were selected from the list of top-sold prescription pharmaceuticals in Belgium. The HILIC separation was optimised to achieve quantification of all analytes in real influent wastewater samples where other compounds, mainly metabolites of some of the pharmaceuticals, were found to interfere even with mass-spectrometric detection in multiple reaction monitoring (MRM) mode. Sample cleanup and preconcentration was based on solid-phase extraction, and Oasis HLB cartridges were chosen after optimization. The method was validated by assessing the following parameters: specificity, selectivity, lower limit of quantification (LLOQ), linearity, accuracy, precision, recovery and matrix effects. For each analyte, LLOQs were sufficiently low to provide a good analytical performance at concentrations expected in real influent samples. Typical LLOQs were 1 ng/L, except for metformin (500 ng/L). Six deuterated analogues were used as internal standards. A total of 22 influent wastewater samples collected from 18 different wastewater treatment plants in Belgium were analysed. Most analytes were present in the samples at concentrations above the LLOQ and were in agreement with other results from the literature. Nebivolol was for the first time found in influent wastewater. In the future, this analytical method will be used to determine if there is a relationship between pharmaceutical sales figures and concentrations of these compounds in influent wastewater.

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References

  1. Tabak HH, Bunch RL (1970) In: Developments in industrial microbiology. Washington, pp 367

  2. Daughton CG, Ternes TA (1999) Environ Health Perspect 107:907–938

    CAS  Article  Google Scholar 

  3. Fent K, Weston AA, Caminada D (2006) Aquat Toxicol 76:122–159

    CAS  Article  Google Scholar 

  4. Vanderford B, Pearson RA, Rexing DJ, Snyder S (2003) Anal Chem 75:6265–6274

    CAS  Article  Google Scholar 

  5. Zuccato E, Chiabrando C, Castiglioni S, Calamari D, Bagnati R, Schiarea S, Fanelli R (2005) Environ Health 4:14–21

    Article  Google Scholar 

  6. Castiglioni S, Zuccato E, Crisci E, Chiabrando C, Fanelli R, Bagnati R (2006) Anal Chem 78:8421–8429

    CAS  Article  Google Scholar 

  7. Hernando MD, Gomez MJ, Aguera A, Fernandez-Alba AR (2007) Trend Anal Chem 26:581–594

    CAS  Article  Google Scholar 

  8. Batt A, Kostich M, Lazorchak JM (2008) Anal Chem 80:5021–5030

    CAS  Article  Google Scholar 

  9. Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2009) Environ Pollut 157:1773–1777

    CAS  Article  Google Scholar 

  10. Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2009) Water Res 43:363–380

    CAS  Article  Google Scholar 

  11. Conley JM, Symes SJ, Schorr MS, Richards SM (2008) Chemosphere 73:1178–1187

    CAS  Article  Google Scholar 

  12. Kuster M, Lopez de Alda MJ, Hernando MD, Petrovic M, Matrin-Alonso J, Barcelo D (2008) J Hydrol 358:112–123

    CAS  Article  Google Scholar 

  13. Busetti F, Linge K, Heitz A (2009) J Chromatogr A 1216:5807–5818

    CAS  Article  Google Scholar 

  14. Benotti M, Trenholm R, Vanderford B, Holady JC, Stanford BD, Snyder SA (2009) Environ Sci Technol 43:597–603

    CAS  Article  Google Scholar 

  15. Ternes TA, Stueber J, Hermann N, McDowell D, Ried A, Kampmann M, Teiser B (2003) Water Res 37:1976–1982

    CAS  Article  Google Scholar 

  16. Radjenovic J, Petrovic M, Barcelo D (2007) Anal Bioanal Chem 387:1365–1377

    CAS  Article  Google Scholar 

  17. Petrovic M, Lopez de Alda MJ, Diaz-Cruz S, Postigo C, Radjenovic J, Gros M, Barcelo D (2009) Phil Trans R Soc A 367:3979–4003

    CAS  Article  Google Scholar 

  18. Rosal R, Rodriguez R, Perdigon-Melon JA, Petre A, Garcia-Calvo E, Gomez MJ, Aguera A, Fernandez-Alba AR (2010) Water Res 44:578–588

    CAS  Article  Google Scholar 

  19. Kümmerer K (2004) Pharmaceuticals in the environment. Sources, fate, effects and risks, 2nd edn. Springer, Heidelberg Berlin

    Google Scholar 

  20. Boxall ABA, Kolpin D, Halling-Sorensen B, Tolls J (2003) Environ Sci Technol 36:286A–294A

    Article  Google Scholar 

  21. Löffler D, Römbke J, Meller M, Ternes TA (2005) Environ Sci Technol 39:5209–5218

    Article  Google Scholar 

  22. Kovalova L, McArdell C, Hollender J (2009) J Chromatogr A 1216:1100–1108

    CAS  Article  Google Scholar 

  23. Qin F, Zhao YY, Sawyer MB, Li XF (2008) Anal Chim Acta 627:91–98

    CAS  Article  Google Scholar 

  24. Peru KM, Kuchta SL, Headley JV, Cessna AJ (2006) J Chromatogr A 1107:152–158

    CAS  Article  Google Scholar 

  25. Gheorghe A, van Nuijs A, Pecceu B, Bervoets L, Jorens PG, Blust R, Neels H, Covaci A (2008) Anal Bioanal Chem 391:1309

    CAS  Article  Google Scholar 

  26. van Nuijs ALN, Tarcomnicu I, Jorens PG, Bervoets L, Blust R, Neels H, Covaci A (2009) Anal Bioanal Chem 395:819–828

    Article  Google Scholar 

  27. Scheurer M, Sacher F, Brauch HI (2009) J Environ Monit 11:1608–1619

    CAS  Article  Google Scholar 

  28. EPA method (1694) http://www.epa.gov/waterscience/methods/method/files/1694.pdf. Accessed 28 June 2010

  29. Official statistics of the Belgian government. http://www.riziv.fgov.be/drug/nl/statistics-scientific-information/pharmanet/pharmaceutical-tables/pdf/2007/tables2007.pdf. Accessed 28 June 2010

  30. WADA Technical Document TD2003IDCR: Identification criteria for qualitative assays. http://www.wada-ama.org/rtecontent/document/criteria_1_2.pdf. Accessed 28 June 2010

  31. European Union Decision 2002/657/EC: The performance of analytical methods and the interpretation of results. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2002:221:0008:0036:EN:PDF. Accessed 28 June 2010

  32. U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for industry: bioanalytical method validation, May 2001. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070107.pdf. Accessed 28 June 2010

  33. Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Anal Chem 75:3019–3030

    CAS  Article  Google Scholar 

  34. Kelly T, Gray TR, Huestis MA (2008) J Chromatogr B 867:194–204

    CAS  Article  Google Scholar 

  35. Robinson M, Horn J (2003) Drugs 63:2739–2754

    CAS  Article  Google Scholar 

  36. Huerta-Fontela M, Galceran MT, Ventura F (2010) J Chromatogr A 1217:4212–4222

    CAS  Article  Google Scholar 

  37. Leverence R, Avery MJ, Kavetskaia O, Bi H, Hop CECA, Gusev AI (2007) Biomed Chromatogr 11:1143–1150

    Article  Google Scholar 

  38. Baselt RC (2004) Disposition of toxic drugs and chemicals in man, 7th edn. Biomedical, Foster City

    Google Scholar 

  39. Gros M, Petrovic M, Barcelo D (2009) Anal Chem 81:898–912

    CAS  Article  Google Scholar 

  40. Laven M, Alsberg T, Yu Y, Adolfsson-Erici J (2009) J Chromatogr A 1216:49–62

    CAS  Article  Google Scholar 

  41. Maurer M, Escher BI, Alder A (2007) Water Res 41:1614–1622

    CAS  Article  Google Scholar 

  42. Wick A, Fink G, Joss A, Siegrist H, Ternes TA (2009) Water Res 43:1060–1074

    CAS  Article  Google Scholar 

  43. Vasskog T, Anderssen T, Pedersen-Bjergaard S, Kallenborn R, Jensen E (2008) J Chromatogr A 1185:194–205

    CAS  Article  Google Scholar 

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Acknowledgements

Alexander van Nuijs and Dr. Adrian Covaci acknowledge the Flanders Scientific Funds for Research (FWO) for their grants. Dr. Isabela Tarcomnicu is grateful to the University of Antwerp for financial support. George Hatfield is acknowledged for his help in preparing the manuscript.

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Affiliations

  1. Toxicological Centre, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium

    Alexander L. N. van Nuijs, Isabela Tarcomnicu, Ward Simons, Hugo Neels & Adrian Covaci

  2. Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium

    Lieven Bervoets, Ronny Blust & Adrian Covaci

  3. Department of Clinical Pharmacology/Clinical Toxicology, University of Antwerp, Antwerp University Hospital, Universiteitsplein 1, 2610, Antwerp, Belgium

    Philippe G. Jorens

Authors
  1. Alexander L. N. van Nuijs
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  2. Isabela Tarcomnicu
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  3. Ward Simons
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  4. Lieven Bervoets
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  6. Philippe G. Jorens
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  7. Hugo Neels
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  8. Adrian Covaci
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Correspondence to Alexander L. N. van Nuijs.

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van Nuijs, A.L.N., Tarcomnicu, I., Simons, W. et al. Optimization and validation of a hydrophilic interaction liquid chromatography–tandem mass spectrometry method for the determination of 13 top-prescribed pharmaceuticals in influent wastewater. Anal Bioanal Chem 398, 2211–2222 (2010). https://doi.org/10.1007/s00216-010-4101-1

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  • DOI: https://doi.org/10.1007/s00216-010-4101-1

Keywords

  • Pharmaceuticals
  • Metabolites
  • Influent wastewater
  • HILIC-MS/MS
  • SPE
  • Validation