Skip to main content
SpringerLink
Log in

Multi-residue enantiomeric analysis of human and veterinary pharmaceuticals and their metabolites in environmental samples by chiral liquid chromatography coupled with tandem mass spectrometry detection

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

Abstract

Enantiomeric profiling of chiral pharmacologically active compounds (PACs) in the environment has hardly been investigated. This manuscript describes, for the first time, a multi-residue enantioselective method for the analysis of human and veterinary chiral PACs and their main metabolites from different therapeutic groups in complex environmental samples such as wastewater and river water. Several analytes targeted in this paper have not been analysed in the environment at enantiomeric level before. These are aminorex, carboxyibuprofen, carprofen, cephalexin, 3-N-dechloroethylifosfamide, 10,11-dihydro-10-hydroxycarbamazepine, dihydroketoprofen, fenoprofen, fexofenadine, flurbiprofen, 2-hydroxyibuprofen, ifosfamide, indoprofen, mandelic acid, 2-phenylpropionic acid, praziquantel and tetramisole. The method is based on chiral liquid chromatography utilising a chiral α1-acid glycoprotein column and tandem mass spectrometry detection. Excellent chromatographic separation of enantiomers (Rs≥1.0) was achieved for chloramphenicol, fexofenadine, ifosfamide, naproxen, tetramisole, ibuprofen and their metabolites: aminorex and dihydroketoprofen (three of four enantiomers), and partial separation (Rs = 0.7–1.0) was achieved for ketoprofen, praziquantel and the following metabolites: 3-N-dechloroethylifosfamide and 10,11-dihydro-10-hydroxycarbamazepine. The overall performance of the method was satisfactory for most of the compounds targeted. Method detection limits were at low nanogram per litre for surface water and effluent wastewater. Method intra-day precision was on average under 20 % and sample pre-concentration using solid phase extraction yielded recoveries >70 % for most of the analytes. This novel, selective and sensitive method has been applied for the quantification of chiral PACs in surface water and effluent wastewater providing excellent enantioresolution of multicomponent mixtures in complex environmental samples. It will help with better understanding of the role of individual enantiomers in the environment and will enable more accurate environmental risk assessment.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Santos LHMLM, Araújo AN, Fachini A, Pena A, Delerue-Matos C, Montenegro MCBSM (2010) Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment. J Hazard Mater 175:45–95

    Article  CAS  Google Scholar 

  2. Celiz MD, Tso J, Aga DS (2009) Pharmaceutical metabolites in the environment: analytical challenges and ecological risks. Environ Toxicol Chem 28:2473–2484

    Article  CAS  Google Scholar 

  3. Clarke BO, Smith SR (2011) Review of “emerging” organic contaminants in biosolids and assessment of international research priorities for the agricultural use of biosolids. Environ Int 37:226–247

    Article  CAS  Google Scholar 

  4. Camacho-Muñoz MD, Santos JL, Aparicio I, Alonso E (2010) Presence of pharmaceutically active compounds in Doñana Park (Spain) main watersheds. J Hazard Mater 177:1159–1162

    Article  Google Scholar 

  5. Martín J, Camacho-Muñoz D, Santos JL, Aparicio I, Alonso E (2012) Occurrence of pharmaceutical compounds in wastewater and sludge from wastewater treatment plants: removal and ecotoxicological impact of wastewater discharges and sludge disposal. J Hazard Mater 239–240:40–47

    Article  Google Scholar 

  6. Camacho-Muñoz D, Martín J, Santos JL, Aparicio I, Alonso E (2012) Effectiveness of conventional and low-cost wastewater treatments in the removal of pharmaceutically active compounds. Water Air Soil Pollut 223:2611–2621

    Article  Google Scholar 

  7. Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2009) The removal of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs during wastewater treatment and its impact on the quality of receiving waters. Water Res 43:363–380

    Article  CAS  Google Scholar 

  8. Carvalho PN, Pirra A, Basto MCP, Almeida CMR (2013) Activated sludge systems removal efficiency of veterinary pharmaceuticals from slaughterhouse wastewater. Environ Sci Pollut Res 20:8790–8800

    Article  CAS  Google Scholar 

  9. Zhou LJ, Ying GG, Liu S, Zhao JL, Chen F, Zhang RQ, Peng FQ, Zhang QQ (2012) Simultaneous determination of human and veterinary antibiotics in various environmental matrices by rapid resolution liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr A 1244:123–138

    Article  CAS  Google Scholar 

  10. Martín J, Camacho-Muñoz MD, Santos JL, Aparicio I, Alonso E (2012) Distribution and temporal evolution of pharmaceutically active compounds alongside sewage sludge treatment. Risk assessment of sludge application onto soils. J Environ Manag 102:18–25

    Article  Google Scholar 

  11. Nguyen LA, He H, Pham-Huy C (2006) Chiral drugs: an overview. Int J Biomed Sci 2:85–100

    CAS  Google Scholar 

  12. Kasprzyk-Hordern B (2010) Pharmacologically active compounds in the environment and their chirality. Chem Soc Rev 39:4466–4503

    Article  CAS  Google Scholar 

  13. Petrie B, Camacho-Muñoz D, Castrignanò E, Evans S, Kasprzyk-Hordern B (2015) Spectrometry for environmental analysis of pharmacologically active compounds chiral liquid chromatography coupled with tandem mass. LC-GC Europe 28:151–160

    Google Scholar 

  14. López-Serna R, Kasprzyk-Hordern B, Petrović M, Barceló D (2013) Multi-residue enantiomeric analysis of pharmaceuticals and their active metabolites in the Guadalquivir River basin (South Spain) by chiral liquid chromatography coupled with tandem mass spectrometry. Anal Bioanal Chem 405:5859–5873

    Article  Google Scholar 

  15. Kasprzyk-Hordern B, Kondakal VVR, Baker DR (2010) Enantiomeric analysis of drugs of abuse in wastewater by chiral liquid chromatography coupled with tandem mass spectrometry. J Chromatogr A 1217:4575–4586

    Article  CAS  Google Scholar 

  16. Ribeiro AR, Santos LHMLM, Maia AS, Delerue-Matos C, Castro PML, Tiritan ME (2014) Enantiomeric fraction evaluation of pharmaceuticals in environmental matrices by liquid chromatography-tandem mass spectrometry. J Chromatogr A 1363:226–235

  17. Hashim NH, Khan SJ (2011) Enantioselective analysis of ibuprofen, ketoprofen and naproxen in wastewater and environmental water samples. J Chromatogr A 1218:4746–4754

    Article  CAS  Google Scholar 

  18. Bagnall JP, Evans SE, Wort MT, Lubbena T, Kasprzyk-Hordern B (2012) Using chiral liquid chromatography quadrupole time-of-flight mass spectrometry for the analysis of pharmaceuticals and illicit drugs in surface and wastewater at the enantiomeric level. J Chromatogr A 1249:115–129

    Article  CAS  Google Scholar 

  19. Nikolai LN, McClure EL, Macleod SL, Wong CS (2006) Stereoisomer quantification of the beta-blocker drugs atenolol, metoprolol, and propranolol in wastewaters by chiral high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 1131:103–109

    Article  CAS  Google Scholar 

  20. MacLeod SL, Sudhir P, Wong CS (2007) Stereoisomer analysis of wastewater-derived β-blockers, selective serotonin re-uptake inhibitors, and salbutamol by high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 1170:23–33

    Article  CAS  Google Scholar 

  21. Scriba GKE (2012) Chiral recognition mechanisms in analytical separation sciences. Chromatographia 75:815–838

    Article  CAS  Google Scholar 

  22. Wsol V, Skalova L, Szotakova B (2004) Chiral inversion of drugs: coincidence or principle? Curr Drug Metab 5:517–533

    Article  CAS  Google Scholar 

  23. Kasprzyk-Hordern B, Dinsdale RM, Guwya J (2007) Multi-residue method for the determination of basic/neutral pharmaceuticals and illicit drugs in surface water by solid-phase extraction and ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry. J Chromatogr A 1161:132–145

    Article  CAS  Google Scholar 

  24. Michishita T, Franco P, Zhang T (2010) New approaches of LC-MS compatible method development on α1-acid glycoprotein-based stationary phase for resolution of enantiomers by HPLC. J Sep Sci 33:3627–3637

    Article  CAS  Google Scholar 

  25. Barclay VKH, Tyrefors NL, Johansson IM, Pettersson CE (2012) Chiral analysis of metoprolol and two of its metabolites, α-hydroxymetoprolol and deaminated metoprolol, in wastewater using liquid chromatography-tandem mass spectrometry. J Chromatogr A 1269:208–217

    Article  CAS  Google Scholar 

  26. Berendsen BJA, Zuidema T, de Jong J, Stolker LAAM, Nielen MWF (2011) Discrimination of eight chloramphenicol isomers by liquid chromatography tandem mass spectrometry in order to investigate the natural occurrence of chloramphenicol. Anal Chim Acta 700:78–85

    Article  CAS  Google Scholar 

  27. Huang Q, Zhang K, Wang Z, Wang C, Peng X (2012) Enantiomeric determination of azole antifungals in wastewater and sludge by liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem 403:1751–1760

    Article  CAS  Google Scholar 

  28. Narayanan SR (1992) Immobilized proteins as chromatographic supports for chiral resolution. J Pharm Biomed Anal 10:251–262

    Article  CAS  Google Scholar 

  29. Hermansson J, Hermansson I (1994) Dynamic modification of the chiral bonding properties of a CHIRAL-AGP column by organic and inorganic additives: separation of enantiomers of anti-inflammatory drugs. J Chromatogr A 666:181–191

  30. Lavén M, Alsberg T, Yu Y, Adolfsson-Erici M, Sun H (2009) Serial mixed-mode cation- and anion-exchange solid-phase extraction for separation of basic, neutral and acidic pharmaceuticals in wastewater and analysis by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. J Chromatogr A 1216:49–62

    Article  Google Scholar 

  31. Mallet CR, Lu Z, Mazzeo JR (2004) A study of ion suppression effects in electrospray ionization from mobile phase additives and solid-phase extracts. Rapid Commun Mass Spectrom 18:49–58

    Article  CAS  Google Scholar 

  32. Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC−MS/MS. Anal Chem 75:3019–3030

    Article  CAS  Google Scholar 

  33. Cappiello A, Famiglini G, Palma P, Pierini E, Termopoli V, Trufelli H (2008) Overcoming matrix effects in liquid chromatography-mass spectrometry. Anal Chem 80:9343–9348

    Article  CAS  Google Scholar 

  34. Barclay VKH, Tyrefors NL, Johansson IM, Pettersson CE (2012) Trace analysis of fluoxetine and its metabolite norfluoxetine. Part II: enantioselective quantification and studies of matrix effects in raw and treated wastewater by solid phase extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr A 1227:105–114

    Article  CAS  Google Scholar 

  35. Caballo C, Sicilia MD, Rubio S (2015) Enantioselective determination of representative profens in wastewater by a single-step sample treatment and chiral liquid chromatography–tandem mass spectrometry. Talanta 134:325–332

    Article  CAS  Google Scholar 

  36. Buser H-R, Poiger T, Müller MD (1999) Occurrence and environmental behavior of the chiral pharmaceutical drug ibuprofen in surface waters and in wastewater. Environ Sci Technol 33:2529–2535

    Article  CAS  Google Scholar 

  37. Matamoros V, Hijosa M, Bayona JM (2009) Assessment of the pharmaceutical active compounds removal in wastewater treatment systems at enantiomeric level. Ibuprofen and naproxen. Chemosphere 75:200–205

    Article  CAS  Google Scholar 

  38. Wang Z, Huang Q, Yu Y, Wang C, Ou W, Peng X (2013) Stereoisomeric profiling of pharmaceuticals ibuprofen and iopromide in wastewater and river water, China. Environ Geochem Health 35:683–691

    Article  Google Scholar 

  39. Larsson E, Al-Hamimi S, Jönsson JÅ (2014) Behaviour of nonsteroidal anti-inflammatory drugs and eight of their metabolites during wastewater treatment studied by hollow fibre liquid phase microextraction and liquid chromatography mass spectrometry. Sci Total Environ 485-486C:300–308

    Article  Google Scholar 

  40. Khan SJ, Wang L, Hashim NH, Mcdonald JA (2014) Distinct enantiomeric signals of ibuprofen and naproxen in treated wastewater and sewer overflow. Chirality 26:739–746

    Article  CAS  Google Scholar 

  41. Hashim NH, Stuetz RM, Khan SJ (2013) Enantiomeric fraction determination of 2-arylpropionic acids in a package plant membrane bioreactor. Chirality 25:301–307

    Article  CAS  Google Scholar 

  42. Selke S, Scheurell M, Shah MR, Hühnerfuss H (2010) Identification and enantioselective gas chromatographic mass-spectrometric separation of O-desmethylnaproxen, the main metabolite of the drug naproxen, as a new environmental contaminant. J Chromatogr A 1217:419–423

    Article  CAS  Google Scholar 

  43. Golovko O, Kumar V, Fedorova G, Randak T, Grabic R (2014) Seasonal changes in antibiotics, antidepressants/psychiatric drugs, antihistamines and lipid regulators in a wastewater treatment plant. Chemosphere 111:418–426

    Article  CAS  Google Scholar 

  44. Loos R, Carvalho R, António DC, Comero S, Locoro G, Tavazzi S, Paracchini B, Ghiani M, Lettieri T, Blaha L, Jarosova B, Voorspoels S, Servaes K, Haglund P, Fick J, Lindberg RH, Schwesig D, Gawlik BM (2013) EU-wide monitoring survey on emerging polar organic contaminants in wastewater treatment plant effluents. Water Res 47:6475–6487

    Article  CAS  Google Scholar 

  45. Zrnčić M, Gros M, Babić S, Kaštelan-Macan M, Barceló D, Petrović M (2014) Analysis of anthelmintics in surface water by ultra high performance liquid chromatography coupled to quadrupole linear ion trap tandem mass spectrometry. Chemosphere 99:224–232

    Article  Google Scholar 

  46. Thienpont D, Brugmans J, Abadi K, Tanamal S (1969) Tetramisole in the treatment of nematode infections in man. Am J Trop Med Hyg 18:520–525

    CAS  Google Scholar 

  47. Bertucci C, Tedesco D, Fabini E, Di Pietra AM, Rossi F, Garagnani M, Del Borrello E, Andrisano V (2014) Determination of levamisole and tetramisole in seized cocaine samples by enantioselective high-performance liquid chromatography and circular dichroism detection. J Chromatogr A 1363:150–154

    Article  CAS  Google Scholar 

  48. Casale JF, Colley VL, Legatt DF (2012) Determination of phenyltetrahydroimidazothiazole enantiomers (levamisole/dexamisole) in illicit cocaine seizures and in the urine of cocaine abusers via chiral capillary gas chromatography-flame-ionization detection: clinical and forensic perspectives. J Anal Toxicol 36:130–135

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration [Grant agreement 629015, the MC IEF project ‘Chiral veterinary medicines in the environment’]. The support from Wessex Water is also greatly appreciated.

Conflict of interest

The authors declare no conflict of interests.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Bath, Bath, BA2 7AY, UK

    Dolores Camacho-Muñoz & Barbara Kasprzyk-Hordern

Authors
  1. Dolores Camacho-Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Kasprzyk-Hordern
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barbara Kasprzyk-Hordern.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 559 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Camacho-Muñoz, D., Kasprzyk-Hordern, B. Multi-residue enantiomeric analysis of human and veterinary pharmaceuticals and their metabolites in environmental samples by chiral liquid chromatography coupled with tandem mass spectrometry detection. Anal Bioanal Chem 407, 9085–9104 (2015). https://doi.org/10.1007/s00216-015-9075-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-015-9075-6

Keywords

Search

Navigation