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.
Similar content being viewed by others
References
Toppari J, Skakkebaek NE (1998) Sexual differentiation and environmental endocrine disrupters. Baillieres Clin Endocrinol Metab 12(1):143–156
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
Scholz S, Kluver N (2009) Effects of endocrine disrupters on sexual, gonadal development in fish. Sex Dev 3(2–3):136–151
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
Odermatt A, Gumy C (2008) Glucocorticoid and mineralocorticoid action: why should we consider influences by environmental chemicals? Biochem Pharmacol 76(10):1184–1193
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
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
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
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
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
Duclos M (2010) Glucocorticoids: a doping agent? Endocrinol Metab Clin N Am 39(1):107–126
Hauri U, Hohl C (2004) Determination of clandestine corticosteroids in cosmetics with LC/DAD/MS. Mitt Lebensm Hyg 95(5):466–476
Kolkhof P, Borden SA (2012) Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics. Mol Cell Endocrinol 350(2):310–317
Czock D, Keller F, Rasche FM, Haussler U (2005) Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 44(1):61–98
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
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
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
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
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
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
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
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
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
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
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
Walker EA, Stewart PM (2003) 11 Beta-hydroxysteroid dehydrogenase: unexpected connections. Trends Endocrinol Metab 14(7):334–339
Johansson M, Nilsson S, Lund BO (1998) Interactions between methylsulfonyl PCBs and the glucocorticoid receptor. Environ Health Perspect 106(12):769–772
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
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)
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
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
Swissmedic (2011) Authorized medicines, procedures and effective ingredients. http://www.swissmedic.ch/daten/00080/00251/indexhtml?lang=en. Accessed 8 Sept 2011
Kohn JA, Deshpande K, Ortlund EA (2012) Deciphering modern glucocorticoid cross-pharmacology using ancestral corticosteroid receptors. J Biol Chem 287(20):16267–16275
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
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
Odermatt A (2004) Corticosteroid-dependent hypertension: environmental influences. Swiss Med Weekly 134(1–2):4–13
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
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
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
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
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
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
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
Corresponding author
Rights and permissions
About this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-014-8206-9