Chiral pharmaceuticals and illicit drugs stereoselective degradation in activated sludge: Methodology and results of quantification in microcosm study

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 illicits, are chiral i.e. the structures can be present in two or more nonsuperimposable 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 switching and preferential metabolism often results 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, are well recognised in drug development 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 introduces the detection of chiral drugs within the environment and details the
analytical technique, chiral LC-MS/MS, used to quantify a range of drugs, including anti-depressants, beta-blockers and illicits, at the enantiomeric level. In addition it will detail the sample preparation techniques used prior to analysis for liquid and solid matrices, e.g. microwave assisted extraction and SPE; illustrating the challenges associated with this, particularly combining the requirements of SPE with chiral-LC. The presented results indicate changes in the
enantiomeric fraction during activated sludge treatment.

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_gui
deline/2009/10/WC500003978.pdf.