Chiral illicit drugs and pharmaceuticals – stereoselective degradation, and its implications for analysis, toxicology and regulatory frameworks

Pharmaceuticals are routinely found within aquatic ecosystems, entering, usually, via wastewater treatment plant (WWTP) effluent, however chirality is rarely considered. Many drugs, including pharmaceuticals and illicit drugs, are chiral i.e. the structures can be present in two or more non-superimposable mirror images, each of which is known as an enantiomer. Each enantiomer, due to its configuration, interacts with biological systems in a unique way. This often results in different adsorption, distribution, metabolic pathways and excretion rates (ADME). Consequently potencies, toxicities and even modes of action may differ between enantiomers. The ADME may also alter when the enantiomers are used in combination due to potential synergistic and/or competitive relationships between the two enantiomers.
Post administration, in vivo chiral inversion and preferential metabolism often result in an altered enantiomeric fraction being excreted. This new mix of enantiomers is then exposed to biological treatment at WWTPs and ad hoc degradation within aquatic ecosystems, which may continually change the enantiomeric fraction.

Chirality, and its implications, is well recognised in drug development and clinical studies with each enantiomer and the mixture being assessed separately. However this phenomenon is not taken into consideration within the European Medicines Agency Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use [1].


This presentation discusses:
1. New enantioselective methodology utilising chiral liquid chromatography coupled with tandem mass spectrometry for the analysis of chiral drugs (anti-depressants, beta-blockers, illicit drugs an analgesic and bronchodilator) in environmental matrices (incl. wastewater and sludge).
2. Stereoselective fate of chiral drugs in river microcosms. The presented results indicate changes in the enantiomeric fraction and highlight why assessing parent drugs in ecotoxicity risk assessments, as is the current practice, may not be appropriate.


[1]European Medicines Agency, Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use, 2006: London, available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500003978.pdf.