Analytical and Bioanalytical Chemistry

, Volume 405, Issue 29, pp 9509–9521 | Cite as

The determination of pharmaceutical residues in cooked and uncooked marine bivalves using pressurised liquid extraction, solid-phase extraction and liquid chromatography–tandem mass spectrometry

  • Gillian McEneffEmail author
  • Leon Barron
  • Brian Kelleher
  • Brett Paull
  • Brian Quinn
Research Paper


An optimised and validated method for the determination of pharmaceutical residues in blue mussels (Mytilus spp.) is presented herein, as well as an investigation of the effect of cooking (by steaming) on any potential difference in human exposure risk. Selected pharmaceuticals included two non-steroidal anti-inflammatory drugs (diclofenac and mefenamic acid), an antibiotic (trimethoprim), an anti-epileptic (carbamazepine) and a lipid regulator (gemfibrozil). An in vivo exposure experiment was set up in the laboratory in which mussels were exposed either directly by injection (10 ng) or daily through spiked artificial seawater (ASW) over 96 h. In liquid matrices, pharmaceutical residues were either determined using liquid chromatography–tandem mass spectrometry (LC-MS/MS) directly, or in combination with solid-phase extraction (SPE) for analyte concentration purposes. The extraction of pharmaceuticals from mussel tissues used an additional pressurised liquid extraction step prior to SPE and LC-MS/MS. Limits of quantification of between 2 and 46 ng L−1 were achieved for extracted cooking water and ASW, between 2 and 64 μg L−1 for ASW in exposure tanks, and between 4 and 29 ng g−1 for mussel tissue. Method linearities were achieved for pharmaceuticals in each matrix with correlation coefficients of R 2 > 0.975. A selection of exposed mussels was also cooked (via steaming) and analysed using the optimised method to observe any effect on detectable concentrations of parent pharmaceuticals present. An overall increase in pharmaceutical residues in the contaminated mussel tissue and cooking water was observed after cooking.


Pharmaceutical residues in cooked and uncooked marine bivalves


Pharmaceuticals Marine bivalves Liquid chromatography Mass spectrometry Bioconcentration Cooking 



The authors would like to thank Lynn Vanhaecke and Julie Kiebooms of Ghent University for their assistance with method development. This report is published as part of the Science, Technology, Research and Innovation for the Environment (STRIVE) Programme 2007–2013 which is funded by the Irish Government under the National Development Plan 2007–2013 and administered on behalf of the Department of the Environment, Heritage and Local Government by the Environmental Protection Agency. This research is also partly funded by Science Foundation of Ireland (Grant Number 08/SRC/B1412).


  1. 1.
    Hernando MD, Mezcua M, Fernandez-Alba AR, Barcelo D (2006) Talanta 69:334–342CrossRefGoogle Scholar
  2. 2.
    Stan HJ, Heberer T (1997) Analusis 25:M20–M23Google Scholar
  3. 3.
    Glassmeyer ST, Kolpin DW, Furlong ET, Focazio MJ (2008) In: Aga DS (ed) Fate of pharmaceuticals in the environment and in water treatment systems. CRC, Boca RatonGoogle Scholar
  4. 4.
    Heberer T, Fuhrmann B, Schmidt-Baumler K, Tsipi D, Koutsouba V, Hiskia A (2000) Abstr Pap Am Chem Soc 219:U623–U623Google Scholar
  5. 5.
    Ternes TA (1998) Water Res 32:3245–3260CrossRefGoogle Scholar
  6. 6.
    Ollers S, Singer HP, Fassler P, Muller SR (2001) J Chromatogr A 911:225–234CrossRefGoogle Scholar
  7. 7.
    Wille K, Noppe H, Verheyden K, Vanden Bussche J, De Wulf E, Van Caeter P, Janssen CR, De Brabander HF, Vanhaecke L (2010) Anal Bioanal Chem 397:1797–1808CrossRefGoogle Scholar
  8. 8.
    Lapworth DJ, Baran N, Stuart ME, Ward RS (2012) Environ Pollut 163:287–303CrossRefGoogle Scholar
  9. 9.
    Adler P, Steger-Hartmann T, Kalbfus W (2001) Acta Hydrochim Hydrobiol 29:227–241CrossRefGoogle Scholar
  10. 10.
    Benotti MJ, Trenholm RA, Vanderford BJ, Holady JC, Stanford BD, Snyder SA (2009) Environ Sci Technol 43:597–603CrossRefGoogle Scholar
  11. 11.
    Huggett DB, Ericson JF, Cook JC, Williams RT (2004) In: Kummerer K (ed) Pharmaceuticals in the environment—sources, fate, effects and risks. Springer, BerlinGoogle Scholar
  12. 12.
    Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD (2004) Aquat Toxicol 68:141–150CrossRefGoogle Scholar
  13. 13.
    Mehinto AC, Hill EM, Tyler CR (2010) Environ Sci Technol 44:2176–2182CrossRefGoogle Scholar
  14. 14.
    Mimeault C, Woodhouse A, Miao XS, Metcalfe CD, Moon TW, Trudeau VL (2005) Aquat Toxicol 73:44–54CrossRefGoogle Scholar
  15. 15.
    Owen SF, Huggett DB, Hutchinson TH, Hetheridge MJ, Kinter LB, Ericson JF, Sumpter JP (2009) Aquat Toxicol 93:217–224CrossRefGoogle Scholar
  16. 16.
    Togunde OP, Oakes KD, Servos MR, Pawliszyn J (2012) Environ Sci Technol 46:5302–5309CrossRefGoogle Scholar
  17. 17.
    Brooks BW, Chambliss CK, Stanley JK, Ramirez A, Banks KE, Johnson RD, Lewis RJ (2005) Environ Toxicol Chem 24:464–469CrossRefGoogle Scholar
  18. 18.
    Chu S, Metcalfe CD (2007) J Chromatogr A 1163:112–118CrossRefGoogle Scholar
  19. 19.
    Schultz MM, Furlong ET, Kolpin DW, Werner SL, Schoenfuss HL, Barber LB, Blazer VS, Norris DO, Vajda AM (2010) Environ Sci Technol 44:1918–1925CrossRefGoogle Scholar
  20. 20.
    Ramirez AJ, Brain RA, Usenko S, Mottaleb MA, O'Donnell JG, Stahl LL, Wathen JB, Snyder BD, Pitt JL, Perez-Hurtado P, Dobbins LL, Brooks BW, Chambliss CK (2009) Environ Toxicol Chem 28:2587–2597CrossRefGoogle Scholar
  21. 21.
    Brown JN, Paxeus N, Forlin L, Larsson DGJ (2007) Environ Toxicol Pharmacol 24:267–274CrossRefGoogle Scholar
  22. 22.
    Fick J, Lindberg RH, Parkkonen J, Arvidsson B, Tysklind M, Larsson DGJ (2010) Environ Sci Technol 44:2661–2666CrossRefGoogle Scholar
  23. 23.
    Clausen I, Riisgard HU (1996) Mar Ecol Prog Ser 141:37–45CrossRefGoogle Scholar
  24. 24.
    Hunt CD, Slone E (2010) Mar Environ Res 70:343–357CrossRefGoogle Scholar
  25. 25.
    Monirith I, Ueno D, Takahashi S, Nakata H, Sudaryanto A, Subramanian A, Karuppiah S, Ismail A, Muchtar M, Zheng JS, Richardson BJ, Prudente M, Hue ND, Tana TS, Tkalin AV, Tanabe S (2003) Mar Pollut Bull 46:281–300CrossRefGoogle Scholar
  26. 26.
    Le Bris H, Pouliquen H (2004) Mar Pollut Bull 48:434–440CrossRefGoogle Scholar
  27. 27.
    Gomez E, Bachelot M, Boillot C, Munaron D, Chiron S, Casellas C, Fenet H (2012) Environ Sci Pollut Res 19:2561–2569CrossRefGoogle Scholar
  28. 28.
    Wille K, Kiebooms JAL, Claessens M, Rappe K, Vanden Bussche J, Noppe H, Van Praet N, De Wulf E, Van Caeter P, Janssen CR, De Brabander HF, Vanhaecke L (2011) Anal Bioanal Chem 400:1459–1472CrossRefGoogle Scholar
  29. 29.
    Bringolf RB, Heltsley RM, Newton TJ, Eads CB, Fraley SJ, Shea D, Cope WG (2010) Environ Toxicol Chem 29:1311–1318Google Scholar
  30. 30.
    Li WH, Shi YL, Gao LH, Liu JM, Cai YQ (2012) Environ Pollut 162:56–62CrossRefGoogle Scholar
  31. 31.
    Steffenak I, Hormazabal V, Yndestad M (1994) Acta Vet Scand 35:299–301Google Scholar
  32. 32.
    Uno K (2002) J Food Hyg Soc of Jpn 43:62–67CrossRefGoogle Scholar
  33. 33.
    Uno K, Aoki T, Kleechaya W, Ruangpan L, Tanasomwang V (2006) Aquac Res 37:826–833CrossRefGoogle Scholar
  34. 34.
    Uno K, Aoki T, Kleechaya W, Tanasomwang V, Ruangpan L (2006) Aquaculture 254:24–31CrossRefGoogle Scholar
  35. 35.
    Uno K, Chaweepack T, Ruangpan L (2010) Aquac Int 18:1003–1015CrossRefGoogle Scholar
  36. 36.
    Primary Care Reimbursement Service: Statistical Analysis of Claims and Payments (2010) Irish Health Service Executive, Dublin. Accessed 2 Aug 2010
  37. 37.
    Prescriptions Dispensed in the Community: England statistics for 1999 to 2009 (2010) The National Health Scheme Information Centre of England, England. Accessed 2 Aug 2010
  38. 38.
    Lacey C, McMahon G, Bones J, Barron L, Morrissey A, Tobin JM (2008) Talanta 75:1089–1097CrossRefGoogle Scholar
  39. 39.
    Bones J, Nesterenko P, Thomas K, Paul B (2006) Int J Environ Anal Chem 86:487–504CrossRefGoogle Scholar
  40. 40.
    Schmidt W, O'Rourke K, Hernan R, Quinn B (2011) Mar Pollut Bull 62:1389–1395CrossRefGoogle Scholar
  41. 41.
    How to cook mussels (2009–2013) Mussel Industry Council of North America. Accessed March 2013
  42. 42.
    Cueva-Mestanza R, Torres-Padron ME, Sosa-Ferrera Z, Santana-Rodriguez JJ (2008) Biomed Chromatogr 22:1115–1122CrossRefGoogle Scholar
  43. 43.
    Barron L, Tobin J, Paull B (2008) J Environ Monit 10:353–361CrossRefGoogle Scholar
  44. 44.
    Jelic A, Petrovic M, Barcelo D (2009) Talanta 80:363–371CrossRefGoogle Scholar
  45. 45.
    Bjorklund E, Nilsson T, Bowadt S (2000) Trends Anal Chem 19:434–445CrossRefGoogle Scholar
  46. 46.
    Runnqvist H, Bak SA, Hansen M, Styrishave B, Halling-Sorensen B, Bjorklund E (2010) J Chromatogr A 1217:2447–2470CrossRefGoogle Scholar
  47. 47.
    Golet EM, Strehler A, Alder AC, Giger W (2002) Anal Chem 74:5455–5462CrossRefGoogle Scholar
  48. 48.
    Hilton MJ, Thomas KV (2003) J Chromatogr A 1015:129–141CrossRefGoogle Scholar
  49. 49.
    Wu JM, Qian XQ, Yang ZG, Zhang LF (2010) J Chromatogr A 1217:1471–1475CrossRefGoogle Scholar
  50. 50.
    Ramirez AJ, Mottaleb MA, Brooks BW, Chambliss CK (2007) Anal Chem 79:3155–3163CrossRefGoogle Scholar
  51. 51.
    Fatta-Kassinos D, Meric S, Nikolaou A (2011) Anal Bioanal Chem 399:251–275CrossRefGoogle Scholar
  52. 52.
    Larsson DGJ, de Pedro C, Paxeus N (2007) J Hazard Mater 148:751–755CrossRefGoogle Scholar
  53. 53.
    Huerta B, Rodríguez-Mozaz S, Barceló D (2012) Anal Bioanal ChemGoogle Scholar
  54. 54.
    Van Der Oost R, Beyer J, Vermeulen NPE (2003) Environ Toxicol Pharmacol 13:57–149CrossRefGoogle Scholar
  55. 55.
    Bremle G, Okla L, Larsson P (1995) Environ Sci Technol 29:2010–2015CrossRefGoogle Scholar
  56. 56.
    Nakamura Y, Yamamoto H, Sekizawa J, Kondo T, Hirai N, Tatarazako N (2008) Chemosphere 70:865–873CrossRefGoogle Scholar
  57. 57.
    Rendal C, Kusk KO, Trapp S (2011) Environ Toxicol Chem 30:354–359CrossRefGoogle Scholar
  58. 58.
    Lahti M, Brozinski JM, Jylha A, Kronberg L, Oikari A (2011) Environ Toxicol Chem 30:1403–1411CrossRefGoogle Scholar
  59. 59.
    Horng H, Spahn-Langguth H, Benet LZ (2013) In: Kaplowitz N, DeLeve LD (eds) Drug-induced liver disease, 3rd edn. Elsevier, San DiegoGoogle Scholar
  60. 60.
    Kallio JM, Lahti M, Oikari A, Kronberg L (2010) Environ Sci Technol 44:7213–7219CrossRefGoogle Scholar
  61. 61.
    Mano Y, Usui T, Kamimura H (2007) Drug Metab Dispos 35:2040–2044CrossRefGoogle Scholar
  62. 62.
    Grillo MP, Lohr MT, Wait JCM (2012) Drug Metab Dispos 40:1515–1526CrossRefGoogle Scholar
  63. 63.
    Dodgson KS, Lewis JIM, Spencer B (1953) Biochem J 55:253–259Google Scholar
  64. 64.
    Quinn B, Schmidt W, O'Rourke K, Hernan R (2011) Chemosphere 84:657–663CrossRefGoogle Scholar
  65. 65.
    Barron L, Nesterenko E, Hart K, Power E, Quinn B, Kelleher B, Paull B (2010) Anal Bioanal Chem 397:287–296CrossRefGoogle Scholar
  66. 66.
    Staines AG, Coughtrie MWH, Burchell B (2004) J Pharmacol Exp Ther 311:1131–1137CrossRefGoogle Scholar
  67. 67.
    Mengelers MJB, Kleter GA, Hoogenboom LAP, Kuiper HA, VanMiert A (1997) J Vet Pharmacol Ther 20:24–32CrossRefGoogle Scholar
  68. 68.
    Trontelj J (2012) In: Prasain J (ed) Tandem mass spectrometry—applications and principles. InTech,, Accessed on: 25th May 2013
  69. 69.
    Skonberg C, Olsen J, Madsen KG, Hansen SH, Grillo MP (2008) Expert Opin Drug Metab Toxicol 4:425–438CrossRefGoogle Scholar
  70. 70.
    Nassar A-EF, Kamel AM, Clarimont C (2004) Drug Discov Today 9:1020–1028CrossRefGoogle Scholar
  71. 71.
    Ternes TA, Kreckel P, Mueller J (1999) Sci Total Environ 225:91–99CrossRefGoogle Scholar
  72. 72.
    Jelic A, Gros M, Petrovic M, Ginebreda A, Barcelo D (2012) In: Guasch H, Ginebreda A, Geiszinger A (eds) Emerging and priority pollutants in rivers. Springer, BerlinGoogle Scholar
  73. 73.
    Kitts DD, Yu CWY, Aoyama RG, Burt HM, McErlane KM (1992) J Agric Food Chem 40:1977–1981CrossRefGoogle Scholar
  74. 74.
    Xu DH, Grizzle JM, Rogers WA, Santerre CR (1996) Food Res Int 29:339–344CrossRefGoogle Scholar
  75. 75.
    Huang TS, Du WX, Marshall MR, Wei CI (1997) J Agric Food Chem 45:2602–2605CrossRefGoogle Scholar
  76. 76.
    Kalogeropoulos N, Karavoltsos S, Sakellari A, Avramidou S, Dassenakis M, Scoullos M (2012) Food Chem Toxicol 50:3702–3708CrossRefGoogle Scholar
  77. 77.
    Perello G, Marti-Cid R, Castell V, Llobet JM, Domingo JL (2009) Food Chem Toxicol 47:709–715CrossRefGoogle Scholar
  78. 78.
    Perello G, Marti-Cid R, Llobet JM, Domingo JL (2008) J Agric Food Chem 56:11262–11269CrossRefGoogle Scholar
  79. 79.
    Smith RM (2002) J Chromatogr A 975:31–46CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Gillian McEneff
    • 1
    • 2
    Email author
  • Leon Barron
    • 3
  • Brian Kelleher
    • 1
    • 4
  • Brett Paull
    • 5
  • Brian Quinn
    • 2
    • 6
  1. 1.Irish Separation Science Cluster (ISSC)Dublin City UniversityDublin 9Ireland
  2. 2.Irish Centre for Environmental Toxicology (ICET)Galway-Mayo Institute of TechnologyGalwayIreland
  3. 3.Analytical & Environmental Sciences DivisionSchool of Biomedical Sciences, King’s College LondonLondonUK
  4. 4.School of Chemical SciencesDublin City UniversityDublin 9Ireland
  5. 5.Australian Centre for Research on Separation Science (ACROSS), School of ChemistryUniversity of TasmaniaHobartAustralia
  6. 6.Institute of Biomedical and Environmental Health Research (IBEHR)University of the West of ScotlandPaisleyUK

Personalised recommendations