Skip to main content
Log in

LC-MS/MS determination of potential endocrine disruptors of cortico signalling in rivers and wastewaters

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

An Erratum to this article was published on 26 April 2016

Abstract

A targeted analytical method was established to determine a large number of chemicals known to interfere with the gluco- and mineralocorticoid signalling pathway. The analytes comprise 30 glucocorticoids and 9 mineralocorticoids. Ten out of these corticosteroids were primary metabolites. Additionally, 14 nonsteroids were included. These analytes represent a broader range of possible adverse modes of action than previously reported. For the simultaneous determination of these structurally diverse compounds, a single-step multimode solid-phase extraction and pre-concentration was applied. Extracts were separated by a short linear HPLC gradient (20 min) on a core shell RP column (2.7 μm particle size) and compounds identified and quantified by LC-MS/MS. The method provided excellent retention time reproducibility and detection limits in the low nanograms per litre range. Untreated hospital wastewater, wastewater treatment plant influent, treated effluent and river waters were analysed to demonstrate the applicability of the method. The results show that not all compounds were sufficiently eliminated by the wastewater treatment, resulting in the presence of several steroids (∼20 ng/L) and nonsteroids in the final effluent, some of them at high concentrations up to 200 ng/L. Most of the detected mono-hydroxylated steroidal transformation products were found at significantly higher concentrations than their parent compounds. We therefore recommend to include these potentially bioactive metabolites in environmental toxicity assessment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Toppari J, Skakkebaek NE (1998) Sexual differentiation and environmental endocrine disrupters. Baillieres Clin Endocrinol Metab 12(1):143–156

    Article  CAS  Google Scholar 

  2. Schubert S, Peter A, Burki R, Schonenberger R, Suter MJF, Segner H, Burkhardt-Holm P (2008) Sensitivity of brown trout reproduction to long-term estrogenic exposure. Aquat Toxicol 90(1):65–72

    Article  CAS  Google Scholar 

  3. Scholz S, Kluver N (2009) Effects of endocrine disrupters on sexual, gonadal development in fish. Sex Dev 3(2–3):136–151

    Article  CAS  Google Scholar 

  4. Odermatt A, Gumy C, Atanasov AG, Dzyakanchuk AA (2006) Disruption of glucocorticoid action by environmental chemicals: potential mechanisms and relevance. J Steroid Biochem Mol Biol 102(1–5):222–231

    Article  CAS  Google Scholar 

  5. Odermatt A, Gumy C (2008) Glucocorticoid and mineralocorticoid action: why should we consider influences by environmental chemicals? Biochem Pharmacol 76(10):1184–1193

    Article  CAS  Google Scholar 

  6. Van der Linden SC, Heringa MB, Man HY, Sonneveld E, Puijker LM, Brouwer A, Van der Burg B (2008) Detection of multiple hormonal activities in wastewater effluents and surface water, using a panel of steroid receptor CALUX bioassays. Environ Sci Technol 42(15):5814–5820

    Article  Google Scholar 

  7. Schriks M, Van Leerdam JA, Van Der Linden SC, Van Der Burg B, Van Wezel AP, De Voogt P (2010) High-resolution mass spectrometric identification and quantification of glucocorticoid compounds in various wastewaters in the Netherlands. Environ Sci Technol 44(12):4766–4774

    Article  CAS  Google Scholar 

  8. Fan ZL, Wu SM, Chang H, Hu JY (2011) Behaviors of glucocorticoids, androgens and progestogens in a municipal sewage treatment plant: comparison to estrogens. Environ Sci Technol 45(7):2725–2733

    Article  CAS  Google Scholar 

  9. Kugathas S, Sumpter JP (2011) Synthetic glucocorticoids in the environment: first results on their potential impacts on fish. Environ Sci Technol 45(6):2377–2383

    Article  CAS  Google Scholar 

  10. Kugathas S, Williams RJ, Sumpter JP (2012) Prediction of environmental concentrations of glucocorticoids: the River Thames, UK, as an example. Environ Int 40:15–23

    Article  CAS  Google Scholar 

  11. Duclos M (2010) Glucocorticoids: a doping agent? Endocrinol Metab Clin N Am 39(1):107–126

    Article  CAS  Google Scholar 

  12. Hauri U, Hohl C (2004) Determination of clandestine corticosteroids in cosmetics with LC/DAD/MS. Mitt Lebensm Hyg 95(5):466–476

    CAS  Google Scholar 

  13. Kolkhof P, Borden SA (2012) Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics. Mol Cell Endocrinol 350(2):310–317

    Article  CAS  Google Scholar 

  14. Czock D, Keller F, Rasche FM, Haussler U (2005) Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 44(1):61–98

    Article  CAS  Google Scholar 

  15. Kienle C, Kase R, Werner I (2011) Evaluation of bioassays and wastewater quality: in vitro and in vivo bioassays for the performance review in the project “Strategy MicroPoll”. Swiss centre for applied ecotoxicology. EAWAG-EPFL, Duebendorf

    Google Scholar 

  16. Fatta-Kassinos D, Meric S, Nikolaou A (2011) Pharmaceutical residues in environmental waters and wastewater: current state of knowledge and future research. Anal Bioanal Chem 399(1):251–275

    Article  CAS  Google Scholar 

  17. Liu S, Ying GG, Zhao JL, Chen F, Yang B, Zhou LJ, Lai HJ (2011) Trace analysis of 28 steroids in surface water, wastewater and sludge samples by rapid resolution liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr A 1218(10):1367–1378

    Article  CAS  Google Scholar 

  18. Chang H, Hu J, Shao B (2007) Occurrence of natural and synthetic glucocorticoids in sewage treatment plants and receiving river waters. Environ Sci Technol 41(10):3462–3468

    Article  CAS  Google Scholar 

  19. Piram A, Salvador A, Gauvrit JY, Lanteri P, Faure R (2008) Development and optimisation of a single extraction procedure for the LC/MS/MS analysis of two pharmaceutical classes residues in sewage treatment plant. Talanta 74(5):1463–1475

    Article  CAS  Google Scholar 

  20. Tolgyesi A, Verebey Z, Sharma VK, Kovacsics L, Fekete J (2010) Simultaneous determination of corticosteroids, androgens, and progesterone in river water by liquid chromatography-tandem mass spectrometry. Chemosphere 78(8):972–979

    Article  CAS  Google Scholar 

  21. Herrero P, Borrull F, Pocurull E, Marcé RM (2012) Determination of glucocorticoids in sewage and river waters by ultra-high performance liquid chromatography–tandem mass spectrometry. J Chromatogr A 1224:19–26

    Article  CAS  Google Scholar 

  22. Spika I, Hammer S, Kleuser B, Korting HC, Schafer-Korting M (2003) Transcriptional activity of potent glucocorticoids: relevance of glucocorticoid receptor isoforms and drug metabolites. Skin Pharmacol Appl Ski Physiol 16(3):143–150

    Article  CAS  Google Scholar 

  23. Matabosch X, Pozo OJ, Perez-Mana C, Farre M, Marcos J, Segura J, Ventura R (2012) Identification of budesonide metabolites in human urine after oral administration. Anal Bioanal Chem 404(2):325–340

    Article  CAS  Google Scholar 

  24. Bureik M, Hubel K, Dragan CA, Scher J, Becker H, Lenz N, Bernhardt R (2004) Development of test systems for the discovery of selective human aldosterone synthase (CYP11B2) and 11b-hydroxylase (CYP11B1) inhibitors. Discovery of a new lead compound for the therapy of congestive heart failure, myocardial fibrosis and hypertension. Mol Cell Endocrinol 217(1–2):249–254

    Article  CAS  Google Scholar 

  25. Atanasov AG, Tam S, Rocken JM, Baker ME, Odermatt A (2003) Inhibition of 11 beta-hydroxysteroid dehydrogenase type 2 by dithiocarbamates. Biochem Biophys Res Commun 308(2):257–262

    Article  CAS  Google Scholar 

  26. Walker EA, Stewart PM (2003) 11 Beta-hydroxysteroid dehydrogenase: unexpected connections. Trends Endocrinol Metab 14(7):334–339

    Article  CAS  Google Scholar 

  27. Johansson M, Nilsson S, Lund BO (1998) Interactions between methylsulfonyl PCBs and the glucocorticoid receptor. Environ Health Perspect 106(12):769–772

    Article  CAS  Google Scholar 

  28. Antunes-Fernandes EC, Bovee TFH, Daamen FEJ, Helsdingen RJ, van den Berg M, van Duursen MBM (2011) Some OH-PCBs are more potent inhibitors of aromatase activity and (anti-) glucocorticoids than non-dioxin like (NDL)-PCBs and MeSO2-PCBs. Toxicol Lett 206(2):158–165

    Article  CAS  Google Scholar 

  29. Gumy C, Chandsawangbhuwana C, Dzyakanchuk AA, Kratschmar DV, Baker ME, Odermatt A (2008) Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production. PLoS One 3(10)

  30. Nakanishi T (2008) Endocrine disruption induced by organotin compounds; organotins function as a powerful agonist for nuclear receptors rather than an aromatase inhibitor. J Toxicol Sci 33(3):269–276

    Article  CAS  Google Scholar 

  31. Kern S, Baumgartner R, Helbling DE, Hollender J, Singer H, Loos MJ, Schwarzenbach RP, Fenner K (2010) A tiered procedure for assessing the formation of biotransformation products of pharmaceuticals and biocides during activated sludge treatment. J Environ Monit 12(11):2100–2111

    Article  CAS  Google Scholar 

  32. Swissmedic (2011) Authorized medicines, procedures and effective ingredients. http://www.swissmedic.ch/daten/00080/00251/indexhtml?lang=en. Accessed 8 Sept 2011

  33. Kohn JA, Deshpande K, Ortlund EA (2012) Deciphering modern glucocorticoid cross-pharmacology using ancestral corticosteroid receptors. J Biol Chem 287(20):16267–16275

    Article  CAS  Google Scholar 

  34. Fraser R, Gower DB, Honour JW, Ingram MC, Kicman AT, Makin HLJ, Stewart PM (2010) Analysis of corticosteroids. In: Makin HLJ, Gower DB (eds) Steroid analysis, 2nd edn. Springer, Heidelberg, pp 329–455

    Google Scholar 

  35. Cook CS, Berry LM, Bible RH, Hribar JD, Hajdu E, Liu NW (2003) Pharmacokinetics and metabolism of C-14 eplerenone after oral administration to humans. Drug Metab Dispos 31(11):1448–1455

    Article  CAS  Google Scholar 

  36. Odermatt A (2004) Corticosteroid-dependent hypertension: environmental influences. Swiss Med Weekly 134(1–2):4–13

    CAS  Google Scholar 

  37. Huntscha S, Singer HP, McArdell CS, Frank CE, Hollender J (2012) Multiresidue analysis of 88 polar organic micropollutants in ground, surface and wastewater using online mixed-bed multilayer solid-phase extraction coupled to high performance liquid chromatography–tandem mass spectrometry. J Chromatogr A 1268:74–83

    Article  CAS  Google Scholar 

  38. Flores-Valverde AM, Hill EM (2008) Methodology for profiling the steroid metabolome in animal tissues using ultraperformance liquid chromatography-electrospray-time-of-flight mass spectrometry. Anal Chem 80(22):8771–8779

    Article  CAS  Google Scholar 

  39. Han J, Kalyan S, Prior JC, Borchers CH (2011) Quantitation of urinary 6β-hydroxycortisol and free cortisol by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Clin Exp Pharmacol S2(S2):1

    Google Scholar 

  40. Arthur KE, Wolff JC, Carrier DJ (2004) Analysis of betamethasone, dexamethasone and related compounds by liquid chromatography/electrospray mass spectrometry. Rapid Commun Mass Spectrom 18(6):678–684

    Article  CAS  Google Scholar 

  41. Macikova P, Groh KJ, Schirmer K, Ammann AA, Suter MJF (2014) Endocrine disrupting compounds affecting corticosteroids signaling pathways in Czech and Swiss waters—potential impact on fish. submitted

  42. Escher BI, Baumgartner R, Koller M, Treyer K, Lienert J, McArdell CS (2011) Environmental toxicology and risk assessment of pharmaceuticals from hospital wastewater. Water Res 45(1):75–92

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful for the financial support by the Sciex-NMSch fund (P. Macikova) and the Swiss Federal Office for the Environment (FOEN).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Adrian A. Ammann.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ammann, A.A., Macikova, P., Groh, K.J. et al. LC-MS/MS determination of potential endocrine disruptors of cortico signalling in rivers and wastewaters. Anal Bioanal Chem 406, 7653–7665 (2014). https://doi.org/10.1007/s00216-014-8206-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-014-8206-9

Keywords

Navigation