Log in

A Systematic Review on Distribution and Ecological Risk Assessment for Chiral Pharmaceuticals in Environmental Compartments

  • Review
  • Published:
Reviews of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Chiral pharmaceuticals are an important class of environmental pollutants. Monitoring studies have shown the non-racemic presence of these contaminants in wastewater, sludge and the receiving environment. This review describes the role of chirality in the environment, especially the distribution and toxicities of enantiomers of chiral pharmaceuticals. In the first part, a systematic overview of their distribution in various environmental matrices and the main application of chiral signatures as chemical markers of water contamination are discussed. Available studies mainly focus on four drug groups including NSAIDs, β-blockers, antidepressants and illicit drugs due to their environmental pseudopersistence and ecotoxicological effects. In the second part, a summary of the enantiospecific toxicity data reported for chiral pharmaceuticals is provided. These data are of high value to improve the accuracy of environmental risk assessments in future works. Enantioselective toxicity towards aquatic organisms have been established for ten out of 36 chiral pharmaceuticals measured and detected in wastewater or surface water samples. Their enantioselective biodegradation and ecotoxicity make the risk assessment process highly recommended. The results provided in this review work support the need for new approaches to more accurately determine the toxicological risks associated to the stereochemistry of environmental contaminants.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Andres-Costa MJ, Kathryn P, Sabatini MT, Gee AP, Lewis SE, Pico Y, Kasprzyk-Hordern B (2017) Enantioselective transformation of fluoxetine in water and its ecotoxicological relevance. Sci Rep 7:1–13

    Article  CAS  Google Scholar 

  • Arenas M, Martín J, Santos JL, Aparicio I, Alonso E (2021) Enantioselective behavior of environmental chiral pollutants: a comprehensive review. Crit Rev Environ Sci Technol. https://doi.org/10.1080/10643389.2021.1900764

    Article  Google Scholar 

  • Bagnall JP, Evans SE, Wort MT, Lubben AT, 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 

  • Bagnall J, Malia L, Lubben A, Kasprzyk-Hordern B (2013) Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms. Water Res 47:5708–5718

    Article  CAS  Google Scholar 

  • Baker DR, Kasprzyk-Hordern B (2013) Spatial and temporal occurrence of pharmaceuticals and illicit drugs in the aqueous environment and during wastewater treatment: New developments. Sci Total Environ 454:442–456

    Article  Google Scholar 

  • Bertin S, Yates K, Petrie B (2020) Enantiospecific behaviour of chiral drugs in soil. Environ Pollut 1:1–26

    Google Scholar 

  • 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 

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

    Article  CAS  Google Scholar 

  • Calcaterra A, D’acquarica I (2018) The market of chiral drugs: chiral switches versus de novo enantiomerically pure compounds. J Pharm Biomed Anal 147:323–340

    Article  CAS  Google Scholar 

  • Camacho-Muñoz D, Petrie B, Leopardo L, Proctor K, Rice J, Youdan J, Barden R, Kasprzyk-Hordern B (2019) Stereoisomeric profiling of chiral pharmaceutically active compounds in wastewaters and the receiving environment—a catchment-scale and a laboratory study. Environ Int 127:558–572

    Article  Google Scholar 

  • Castrignanò E, Mardal M, Rydevik A, Miserez B, Ramsey J, Shine T, Panto GD, Meyer MR, Kasprzyk-Hordern B (2017) A new approach towards biomarker selection in estimation of human exposure to chiral chemicals: a case study of mephedrone. Sci Rep 7:13009

    Article  Google Scholar 

  • Castrignanò E, Kannan AM, Feil EJ, Kasprzyk-Hordern B (2018) Enantioselective fractionation of fluoroquinolones in the aqueous environment using chiral liquid chromatography coupled with tandem mass spectrometry. Chemosphere 206:376–386

    Article  Google Scholar 

  • Chai T, Cui F, Di S, Wu S, Zhang Y, Wang X (2021) New insights into cardiotoxicity induced by chiral fluoxetine at environmental-level: Enantioselective arrhythmia in developmental zebrafish (Danio rerio). Environ Pollut 270:116182

    Article  CAS  Google Scholar 

  • Coelho MM, Lado Ribeiro AR, Sousa JCG, Ribeiro C, Fernandes C, Silva AMT, Tiritan ME (2019) Dual enantioselective LC–MS/MS method to analyse chiral drugs in surface water: monitoring in Douro River estuary. J Pharm Biomed Anal 170:89–101

    Article  CAS  Google Scholar 

  • Commission Implementing Decision (EU) 2018/840 of 5 June 2018 establishing a watch list of substances for Union-wide monitoring in the field of water policy pursuant to Directive 2008/105/EC of the European Parliament and of the Council and repealing Commission Implementing Decision (EU) 2015/495 (notified under document C (2018) 3362)

  • Connors KA, Du B, Fitzsimmons PN, Chambliss CK, Nichols JW, Brooks BW (2013) Enantiomer-specific in vitro biotransformation of select pharmaceuticals in rainbow trout (Oncorhynchus mykiss). Chirality 25:763–767

    Article  CAS  Google Scholar 

  • De Andrés F, Castañeda G, Ríos Á (2009) Use of toxicity assays for enantiomeric discrimination of pharmaceutical substances. Chirality 21(8):751–759

    Article  Google Scholar 

  • Dogan A, Płotka-Wasylka J, Kempinska-Kupczyk D, Namie-snik J, Kot-Wasik A (2020) Detection, identification and determination of chiral pharmaceutical residues in wastewater: problems and challenges. Tr Anal Chem 122:115710

    Article  CAS  Google Scholar 

  • Duan L, Zhang Y, Wang B, Deng S, Huang J, Wang Y, Yu G (2018) Occurrence, elimination, enantiomeric distribution and intra-day variations of chiral pharmaceuticals in major wastewater treatment plants in Bei**g, China. Environ Pollut 239:473–482

    Article  CAS  Google Scholar 

  • Eaglesham A, Scott A, Petrie B (2020) Multi-residue enantioselective analysis of chiral drugs in freshwater sediments. Environ Chem Lett 18:2119–2126

    Article  CAS  Google Scholar 

  • European Medicines Agency (EMEA) (2006) Guideline on the environmental risk assessment of medicinal products for human use, C.f.M.P.f.H. use. Editor, London

  • Evans SE, Kasprzyk-Hordern B (2014) Applications of chiral chromatography coupled with mass spectrometry in the analysis of chiral pharmaceuticals in the environment. Tr Environ Anal Chem 1:34–51

    Article  Google Scholar 

  • Evans S, Bagnall J, Kasprzyk-Hordern B (2017) Enantiomeric profiling of a chemically diverse mixture of chiral pharmaceuticals in urban water. Environ Pollut 230:368–377

    Article  CAS  Google Scholar 

  • Fantegrossi WE (2008) In vivo pharmacology of MDMA and its enantiomers in rhesus monkeys. Exp Clin Psychopharmacol 16(1):1–12

    Article  CAS  Google Scholar 

  • Fono LJ, Sedlak DL (2005) Use of the chiral pharmaceutical propranolol to identify sewage discharges into surface waters. Environ Sci Technol 39:9244–9252

    Article  CAS  Google Scholar 

  • Gasser G, Pankratov I, Elhanany S, Werner P, Gun J, Gelman F, Lev O (2012) Field and laboratory studies of the fate and enantiomeric enrichment of venlafaxine and O-desmethylvenlafaxine under aerobic and anaerobic conditions. Chemosphere 88:98–105

    Article  CAS  Google Scholar 

  • Gonçalves R, Ribeiro C, Cravo S, Cunha CS, Pereira JA, Fernandes JO, Afonso C, Tiritan ME (2019) Multi-residue method for enantioseparation of psychoactive substances and beta blockers by gas chromatography–mass spectrometry. J Chromatogr B 1125:121731

    Article  Google Scholar 

  • 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 

  • Hashim NH, Nghiem LD, Stuetz RM, Khan SL (2011) Enantiospecific fate of ibuprofen, ketoprofen and naproxen in a laboratory-scale membrane bioreactor. Water Res 45:6249–6258

    Article  CAS  Google Scholar 

  • Hernando MD, Mezcua M, Fernandez-Alba AR, Barcelo D (2006) Environmental risk assessment of pharmaceutical residues in wastewater effluents, surface waters and sediments. Talanta 69:334–342

    Article  CAS  Google Scholar 

  • Hurtado C, Domínguez C, Pérez-Babace L, Cañameras N, Comas J, Bayona JM (2016) Estimate of uptake and translocation of emerging organic contaminants from irrigation wáter concentration in lettuce grown under controlled conditions. J Hazard Mater 305:139–148

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Kasprzyk-Hordern B, Baker DR (2012) Enantiomeric profiling of chiral drugs in wastewater and receiving waters. Environ Sci Technol 46:1681–1691

    Article  CAS  Google Scholar 

  • 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 

  • Kunkel U, Radke M (2012) Fate of pharmaceuticals in rivers: deriving a benchmark dataset at favorable attenuation conditions. Water Res 46:5551–5565

    Article  CAS  Google Scholar 

  • Li Z, Gomez E, Fenet H, Chiron S (2013) Chiral signature of venlafaxine as a marker of biological attenuation processes. Chemosphere 90:1933–1938

    Article  CAS  Google Scholar 

  • 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 

  • Ma R, Wang B, Lu S, Zhang Y, Yin L, Huang J, Deng S, Wang Y, Yu G (2016) Characterization of pharmaceutically active compounds in Dongting Lake, China: occurrence, chiral profiling and environmental risk. Sci Total Environ 557:268–275

    Article  Google Scholar 

  • Ma R, Qu H, Wang B, Wang F, Yu Y, Yu G (2019) Simultaneous enantiomeric analysis of non-steroidal anti-inflammatory drugs in environment by chiral LC-MS/MS: a pilot study in Bei**g, China. Ecotoxicol Environ Saf 174:83–91

    Article  CAS  Google Scholar 

  • Ma R, Qu H, Wang B, Wang F, Yu G (2020) Widespread monitoring of chiral pharmaceuticals in urban rivers reveals stereospecific occurrence and transformation. Environ Int 178:105657

    Article  Google Scholar 

  • MacLeod SL, Wong CS (2010) Loadings, trends, comparisons, and fate of achiral and chiral pharmaceuticals in wastewaters from urban tertiary and rural aerated lagoon treatments. Water Res 44:533–544

    Article  CAS  Google Scholar 

  • 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—andem mass spectrometry. J Chromatogr A 1170:23–33

    Article  CAS  Google Scholar 

  • Maia AS, Ribeiro AR, Castro PML, Tiritan ME (2017) Chiral analysis of pesticides and drugs of environmental concern: biodegradation and enantiomeric fraction. Symmetry 9:196–225

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Mennillo E, Arukwe A, Monni G, Meucci V, Intorre L, Pretti C (2018) Ecotoxicological properties of ketoprofen and the S(+)-enantiomer (dexketoprofen): bioassays in freshwater model species and biomarkers in fish PLHC-1 cell line. Environ Toxicol Chem 37:201–212

    Article  CAS  Google Scholar 

  • Neale PA, Branch A, Khan SJ, Leusch FDL (2020) Evaluating the enantiospecific differences of non-steroidal anti-inflammatory drugs (NSAIDs) using an ecotoxicity bioassay test battery. Sci Total Environ 694:133659

    Article  Google Scholar 

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

    CAS  Google Scholar 

  • Nikolai LN, McClure EL, MacLeod SL, Wong CS (2006) Stereoisomer quantification of the β-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 

  • Petrie B, Camacho-Muñoz D (2021) Analysis, fate and toxicity of chiral non-steroidal anti-in ammatory drugs in wastewaters and the environment: a review. Environ Chem Lett 19:43–75

    Article  CAS  Google Scholar 

  • Petrie B, Proctor K, Youdan J, Barden R, Kasprzyk-Hordern B (2017) Critical evaluation of monitoring strategy for the multi-residue determination of 90 chiral and achiral micropollutants in effluent wastewater. Sci Total Environ 579:569–578

    Article  CAS  Google Scholar 

  • Qu H, Ma R, Wang B, Yang J, Duan L, Yu G (2019) Enantiospecific toxicity, distribution and bioaccumulation of chiral antidepressant venlafaxine and its metabolite in loach (Misgurnus anguillicaudatus) co-exposed to microplastic and the drugs. J Hazard Mater 370:203–211

    Article  CAS  Google Scholar 

  • Ribeiro AR, Castro PML, Tiritan ME (2012) Chiral pharmaceuticals in the environment. Environ Chem Lett 10:239–253

    Article  CAS  Google Scholar 

  • Ribeiro C, Ribeiro AR, Maia AS, Tiritan ME (2017) Occurrence of chiral bioactive compounds in the aquatic environment: a review. Symmetry 9:215

    Article  CAS  Google Scholar 

  • Ribeiro AR, Maia AS, Tiritan ME (2020) Analysis of chiral drugs in environmental matrices: current knowledge and trends in environmental, biodegradation and forensic fields. Trans Anal Chem 124:115783

    Article  CAS  Google Scholar 

  • Rice J, Proctor K, Lopardo L, Evans S, Kasprzyk-Hordern B (2018) Stereochemistry of ephedrine and its environmental significance: exposure and effects directed approach. J Hazard Mater 348:39–46

    Article  CAS  Google Scholar 

  • Ruan Y, Wu R, Lam JCW, Zhang K, Lam PKS (2019) Seasonal occurrence and fate of chiral pharmaceuticals in different sewage treatment systems in Hong Kong: mass balance, enantiomeric profiling, and risk assessment. Water Res 149:607–616

    Article  CAS  Google Scholar 

  • Ruan Y, Lin H, Zhang X, Wu R, Zhang K, Leung KMY, Lam JCW, Lam PKS (2020) Enantiomer-specific bioaccumulation and distribution of chiral pharmaceuticals in a subtropical marine food web. J Hazard Mater 394:122589

    Article  CAS  Google Scholar 

  • Sanganyado E, Fu Q, Gan J (2016) Enantiomeric selectivity in adsorption of chiral b-blockers on sludge. Environ Pollut 214:787–794

    Article  CAS  Google Scholar 

  • Sanganyado E, Lu Z, Fu Q, Schlenk D, Gan J (2017) Chiral pharmaceuticals: a review on their environmental occurrence and fate processes. Water Res 124:527–542

    Article  CAS  Google Scholar 

  • Santos LH, Araújo AN, Fachini A, Pena A, Delerue-Matos C, Montenegro MS (2010) Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment. J Hazard Mater 175(1–3):45–95

    Article  CAS  Google Scholar 

  • 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 

  • Smith EM, Chu S, Paterson G, Metcalfe CD, Wilson JY (2010) Cross-species comparison of fluoxetine metabolism with fish liver microsomes. Chemosphere 79:26–32

    Article  CAS  Google Scholar 

  • Song Y, Chai T, Yin Z, Zhang X, Zhang X, Qian Y, Qiu J (2018) Stereoselective effects of ibuprofen in adult zebrafish (Danio rerio) using UPLC-TOF/MS-based metabolomics. Environ Pollut 241:730–739

    Article  CAS  Google Scholar 

  • Souchier M, Benali-Raclot D, Casellas C, Ingrand V, Chiron S (2016) Enantiomeric fractionation as a tool for quantitative assessment of biodegradation: the case of metoprolol. Water Res 95:19–26

    Article  CAS  Google Scholar 

  • Stanley JK, Brooks BW (2009) Perspectives on ecological risk assessment of chiral compounds. Integr Environ Assess Manag 5:364–373

    Article  CAS  Google Scholar 

  • Stanley JK, Ramirez AJ, Mottaleb M, Chambliss CK, Brooks BW (2006) Enantiospecific toxicity of the β-blocker propranolol to Daphnia magna and Pimephales promelas. Environ Toxicol Chem 25:1780–1786

    Article  CAS  Google Scholar 

  • Stanley JK, Ramirez AJ, Chambliss CK, Brooks BW (2007) Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate. Chemosphere 69(1):9–16

    Article  CAS  Google Scholar 

  • Sun L, **n L, Peng Z, ** R, ** Y, Qian H, Fu Z (2014) Toxicity and enantiospecific differences of two b-blockers, propranolol and metoprolol, in the embryos and larvae of zebrafish (Danio rerio). Environ Toxicol 29(12):1367–1378

    Article  CAS  Google Scholar 

  • Suzuki T, Kosugi Y, Hosaka M, Nishimura T, Nakaey D (2014) Occurrence and behaviour of the chiral anti-inflammatory drug naproxen in an aquatic environment. Environ Toxicol Chem 33:2671–2678

    Article  CAS  Google Scholar 

  • Wang F, Wang B, Qu H, Zhao W, Duan L, Zhang Y, Zhou Y, Yu G (2020) The influence of nanoplastics on the toxic effects, bio-accumulation, biodegradation and enantioselectivity of ibuprofen in freshwater algae Chlorella pyrenoidosa. Environ Pollut 263:114593

    Article  CAS  Google Scholar 

  • Zhang W, Song Y, Chai T, Liao G, Zhang L, Jia Q, Qian Y, Qiu J (2020) Lipidomics perturbations in the brain of adult zebrafish (Danio rerio) after exposure to chiral ibuprofen. Sci Total Environ 713:136565

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the Ministerio de Ciencia e Innovación (Project No. PID2020-117641RB-I00) and the Junta de Andalucía, Consejería de Economía y Conocimiento (Project No. US-1254283).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Julia Martín.

Ethics declarations

Conflict of interest

Authors declare that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mejías, C., Arenas, M., Martín, J. et al. A Systematic Review on Distribution and Ecological Risk Assessment for Chiral Pharmaceuticals in Environmental Compartments. Reviews Env.Contamination (formerly:Residue Reviews) 260, 3 (2022). https://doi.org/10.1007/s44169-021-00003-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s44169-021-00003-5

Navigation