Advertisement

Analytical and Bioanalytical Chemistry

, Volume 398, Issue 3, pp 1207–1229 | Cite as

Anabolic, doping, and lifestyle drugs, and selected metabolites in wastewater—detection, quantification, and behaviour monitored by high-resolution MS and MS n before and after sewage treatment

  • Horst Fr. Schröder
  • Wilhelm Gebhardt
  • Mario Thevis
Original Paper

Abstract

Municipal wastewater has been examined for steroids, β2-agonists, stimulants, diuretics, and phosphodiesterase type V inhibitors (PDE type V inhibitors), which are “dual-use-drugs” applied either as anabolic, doping, and lifestyle drugs or for treatment of diverse diseases. To identify their origin, fitness centre discharges under suspicion of being point sources and sewage-treatment plant feed and effluents were sampled and concentrations determined. Sensitive and selective methods for determination and quantification based on solid-phase extraction (SPE) followed by high-performance liquid chromatography–high resolution mass and tandem mass spectrometry (HPLC–(HR)MS and HPLC–MS–MS) were developed and established for analysis of these compounds in wastewater and to assess their effect on the environment. The methods developed enabled quantification at trace concentrations (limit of quantification (LOQ): 5 ng L−1). Of the steroids and stimulants under investigation, testosterone, methyltestosterone, and boldenone or ephedrine, amphetamine, and MDMA (3,4-methylendioxy-N-methylamphetamine) were observed at up to 5 μg L−1 (ephedrine). Of the β2-agonists salbutamol only, and of the diuretics furosemide and hydrochlorothiazide were confirmed in the extracts. Quite high concentrations of the PDE type V inhibitors sildenafil, tadalafil, and vardenafil and their metabolites were confirmed in fitness centre discharges (sildenafil: 1,945 ng L−1) whereas their concentrations in municipal wastewater did not exceed 35 ng L−1. This study identified anabolic and doping drugs in wastewater for the first time. Results obtained from wastewater treatment plant effluents proved that these “dual-use-drugs”, with the exception of hydrochlorothiazide, were mostly eliminated.

Figure

Anabolic, doping and lifestyle drugs on their ways into the environment

Keywords

Anabolic Doping Lifestyle drugs Wastewater LC–MS LC–MSn Elimination Degradation 

Notes

Acknowledgements

The authors thank the employees of the workshop of the Institute of Environmental Engineering for their fruitful support during wastewater sample collection.

Supplementary material

216_2010_3958_MOESM1_ESM.pdf (480 kb)
ESM 1 (PDF 479 kb)

References

  1. 1.
    Ternes TA (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32:3245–3260CrossRefGoogle Scholar
  2. 2.
    Körner W, Bolz U, Süßmuth W, Hiller G, Schuller W, Hanf V, Hagenmaier H (2000) Input/output balance of estrogenic active compounds in a major municipal sewage plant in Germany. Chemosphere 40:1131–1142CrossRefGoogle Scholar
  3. 3.
    Ternes TA (2001) Analytical methods for the determination of pharmaceuticals in aqueous environmental samples. Trends Anal Chem 20:419–434CrossRefGoogle Scholar
  4. 4.
    Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: a national reconnaissance. Environ Sci Technol 36:1202–1211CrossRefGoogle Scholar
  5. 5.
    Calamari D, Zuccato E, Castiglioni S, Bagnati R, Fanelli R (2003) Strategic survey of therapeutic drugs in the Rivers Po and Lambro in Northern Italy. Environ Sci Technol 37:1241–1248CrossRefGoogle Scholar
  6. 6.
    Rodriguez-Mozaz S, Lopes de Alda MJ, Barceló D (2004) Picogram per liter level determination of estrogens in natural waters and waterworks by a fully automated on-line solid-phase extraction–liquid chromatography–electrospray tandem mass spectrometry method. Anal Chem 76:6998–7006CrossRefGoogle Scholar
  7. 7.
    Zuccato E, Chiabrando C, Castiglioni S, Calamari D, Bagnati R, Schiarea S, Fanelli R (2005) Cocaine in surface waters: a new evidence-based tool to monitor community drug abuse. Environ Health 4:14. doi: 10.1186/1476-069X-4-14 CrossRefGoogle Scholar
  8. 8.
    Castiglioni S, Zuccato E, Crisci E, Chiabrando Ch, Fanelli R, Bagnati R (2006) Identification and measurement of illicit drugs their metabolites in urban wastewater by liquid chromatography–tandem mass spectrometry. Anal Chem 78:8421–8429CrossRefGoogle Scholar
  9. 9.
    Hummel D, Löffler D, Fink G, Ternes TA (2006) Simultaneous determination of psychoactive drugs and their metabolites in aqueous matrices by liquid chromatography mass spectrometry. Environ Sci Technol 40:7321–7328CrossRefGoogle Scholar
  10. 10.
    Huerta-Fontela M, Galceran MT, Ventura F (2007) Ultraperformance liquid chromatography–tandem mass spectrometry analysis of stimulatory drugs of abuse in wastewater and surface waters. Anal Chem 79:3821–3829CrossRefGoogle Scholar
  11. 11.
    Boleda R, Galceran T, Ventura F (2007) Trace determination of cannabinoids and opiates in wastewater and surface waters by ultra-performance liquid chromatography–tandem mass spectrometry. J Chromatogr A 1175:38–48CrossRefGoogle Scholar
  12. 12.
    Bones J, Thomas KV, Paull B (2007) Using environmental analytical data to estimate levels of community consumption of illicit drugs and abused pharmaceuticals. J Environ Monit 9:701–707CrossRefGoogle Scholar
  13. 13.
    Nieto A, Peschka M, Borrull F, Pocurull E, Marcé RM, Knepper TP (2009) Phosphodiesterase type V inhibitors: occurrence and fate in wastewater and sewage sludge. Water Res 44:1607–1615CrossRefGoogle Scholar
  14. 14.
    Gebhardt W, Thevis M, Schröder HFr (2008) Occurrence and follow-up of anabolic and doping drugs during wastewater treatment by means of high resolution liquid chromatography–mass spectrometry (LC–MS and –MSn). Oral presentation during “25th Montreux Symposium on LC–MS–MS”; 12.–14.11.2008 in Montreux (Switzerland), Proceedings p 17Google Scholar
  15. 15.
    Hemmersbach P, de la Torre R (1996) Stimulants, narcotics and β-blockers: 25 years of development in analytical techniques for doping control. J Chromatogr B 687:221–238CrossRefGoogle Scholar
  16. 16.
    Holt RIG, Erotokritou-Mulligan I, Sonksen PH (2009) The history of doping and growth hormone abuse in sport. Growth Horm IGF Res 19:320–326CrossRefGoogle Scholar
  17. 17.
    Hemmersbach P (2008) History of mass spectrometry at the Olympic Games. J Mass Spectrom 43:839–853CrossRefGoogle Scholar
  18. 18.
    Guermouche MH, Bensalah K (2006) Solid phase extraction and liquid chromatographic determination of sildenafil and N-demethylsidenafil in rat serum with basic mobile phase. J Pharmceut Biomed 40:952–957CrossRefGoogle Scholar
  19. 19.
    Thevis M, Schänzer W (2005) Examples of doping control analysis by liquid chromatography–tandem mass spectrometry: ephedrines, beta-receptor blocking agents, diuretics, sympathomimetics, and cross-linked hemoglobins. J Chromatogr Sci 43:22–31Google Scholar
  20. 20.
    Gergov M, Ojanperä I, Vuori E (2003) Simultaneous screening for 238 drugs in blood by liquid chromatography–ionspray tandem mass spectrometry with multiple-reaction monitoring. J Chromatogr B 795:41–53CrossRefGoogle Scholar
  21. 21.
    Weinmann W, Goerner M, Vogt S, Goerke R, Pollak S (2001) Fast confirmation of 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in urine by LC–MS–MS using negative atmospheric-pressure chemical ionisation (APCI). Forensic Sci Int 121:103–107CrossRefGoogle Scholar
  22. 22.
    Concheiro M, de Castro A, Quintela O, Cruz A, Lopez-Rivadulla M (2004) Development and validation of a method for the quantitation of Δ9tetrahydrocannabinol in oral fluid by liquid chromatography electrospray–mass-spectrometry. J Chromatogr B 810:319–324Google Scholar
  23. 23.
    Teixeira H, Proença P, Verstraete A, Corte-Real F, Vieira DN (2005) Analysis of Delta(9)-tetrahydrocannabinol in oral fluid samples using solid-phase extraction and high-performance liquid chromatography–electrospray ionization mass spectrometry. Forensic Sci Int 150:205–211CrossRefGoogle Scholar
  24. 24.
    Laloup M, del Mar Ramirez FM, Wood M, De Boeck G, Henquet C, Maes V, Samyn N (2005) Quantitative analysis of Δ9-tetrahydrocannabinol in preserved oral fluid by liquid chromatography–tandem mass spectrometry. J Chromatogr A 1082:15–24CrossRefGoogle Scholar
  25. 25.
    Maralikova B, Weinmann W (2004) Simultaneous determination of Delta(9)-tetrahydrocannabinol, 11-hydroxy-Delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol in human plasma by high-performance liquid chromatography/tandem mass spectrometry. J Mass Spectrom 39:526–531CrossRefGoogle Scholar
  26. 26.
    Maralikova B, Weinmann W (2004) Confirmatory analysis for drugs of abuse in plasma and urine by high-performance liquid chromatography–tandem mass spectrometry with respect to criteria for compound identification. J Chromatogr B 811:21–30Google Scholar
  27. 27.
    Choo RE, Murphy CM, Jones HE, Huestis MA (2005) (2005) Determination of methadone, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine, 2-ethyl-5-methyl-3, 3-diphenylpyraline and methadol in meconium by liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr B 814:369–373CrossRefGoogle Scholar
  28. 28.
    Wood M, Laloup M, del Mar Ramirez FM, Jenkins KM, Young MS, Ramaekers JG, De Boeck G, Samun N (2005) Quantitative analysis of multiple illicit drugs in preserved oral fluid by solid-phase extraction and liquid chromatography–tandem mass spectrometry. Forensic Sci Int 150:227–238CrossRefGoogle Scholar
  29. 29.
    Wood M, Laloup M, Samyn N, del Mar Ramirez FM, de Bruijin EA, Maes RAA, De Boeck G (2006) Recent applications of liquid chromatography–mass spectrometry in forensic science. J Chromatogr A 1130:3–15CrossRefGoogle Scholar
  30. 30.
    European Union Decision 2002/657/EC (2002) Commission decision of 12 August 2002 implementing Council Directive 96/23/EC concerning the performance of analytical methods and the interpretation of results. Off J Eur Commun 221(482):8–38Google Scholar
  31. 31.
    Rivier L (2003) Criteria for the identification of compounds by liquid chromatography–mass spectrometry and liquid chromatography–multiple mass spectrometry in forensic toxicology and doping analysis. Anal Chim Acta 492:69–82CrossRefGoogle Scholar
  32. 32.
    Gebhardt W, Schröder HFr (2007) LC–MS and –MS–MS for the Follow-Up of the Elimination of Persistent Pharmaceuticals During Wastewater Treatment Applying Biological Wastewater Treatment and Advanced Oxidation. J Chromatogr A 1160:34–43CrossRefGoogle Scholar
  33. 33.
    Hogenboom AC, van Leerdam JA, de Voogt P (2009) Accurate mass screening and identification of emerging contaminants in environmental samples by liquid chromatography–hybrid linear ion trap Orbitrap mass spectrometry. J Chromatogr A 1216:510–519CrossRefGoogle Scholar
  34. 34.
    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (2005) ICH harmonised tripartite guideline, validation of analytical procedures: methodology (Q2(R1). http://www.ich.org/LOB/media/MEDIA417.pdf, accessed 08.September 2008
  35. 35.
    Kromidas A (1999) Validierung in der Analytik. Wiley-VCH, WeinheimGoogle Scholar
  36. 36.
    Weinmann W, Bohnert M, Wiedemann A, Renz M, Lehmann N, Pollak S (2001) Post-mortem detection and identification of silenafil (viagra) and its metabolites by LC–MS and LC–MS–MS. Int J Leg Med 114:252–258CrossRefGoogle Scholar
  37. 37.
    Kim J, Ji HY, Kim SJ, Lee HW, Lee SS, Kim DS, Yoo M, Kim WB, Lee HS (2003) Simultaneous determination of sildenafil and its active metabolite UK-103, 320 in human plasma using liquid chromatography–tandem mass spectrometry. J Pharm Biomed Anal 32:317–322CrossRefGoogle Scholar
  38. 38.
    Ku HY, Shon JH, Liu KH, Shin JG, Bae SK (2009) Liquid chromatography/tandem mass spectrometry method for the simultaneous determination of vardenafil and its major metabolite, N-desethylvardenafil, in human plasma: application to a pharmacokinetic study. J Chromatogr B 877:95–100CrossRefGoogle Scholar
  39. 39.
    Radjenovic J, Petrovic M, Barceló D (2007) Analysis of pharmaceuticals in wastewater and removal using a membrane bioreactor. Anal Bioanal Chem 387:1365–1377CrossRefGoogle Scholar
  40. 40.
    Radjenovic J, Petrovic M, Barceló D (2009) Fate and distribution of pharmaceuticals in wastewater and sewage sludge of the conventional activated sludge (CAS) and advanced membrane bioreactor (MBR) treatment. Water Res 43:831–841CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Horst Fr. Schröder
    • 1
  • Wilhelm Gebhardt
    • 1
  • Mario Thevis
    • 2
  1. 1.RWTH Aachen UniversityAachenGermany
  2. 2.German Sports University CologneKölnGermany

Personalised recommendations