Stereoselective degradation of chiral drugs during wastewater treatment

Pharmacologically active compounds (PACs) constitute a vast and diverse group of chemicals. Despite low ppt concentrations of these compounds in environmental matrices, PACs pose considerable environmental concern as many of them are active at very low concentrations. Additionally, PACs are present in the environment as multi-residue mixtures, and therefore synergistic effects of PACs should also be considered. Due to the non-volatile nature of the majority of PACs, and their continuous introduction into the environment, their environmental impact cannot be underestimated. PACs have also been detected in drinking water, which poses a direct risk to humans and raises the issue of contaminated water sources and especially water reuse.

Water is a limited resource in an expanding global economy and population. In the future its accessibility will be significantly impacted by changing climate. Reclaiming water for non-potable (irrigation, urban, industrial) or potable purposes is therefore considered to be an important element of sustainable water resource management. There are, however, certain risks associated with water reuse including microbiological and chemical risks (e.g. the presence of PACs in reclaimed water). They have to be verified before water reuse is to be implemented on a wider scale.
Several groups of PACs such as beta-blockers, antibiotics or analgesics have been studied before in the environment but surprisingly their chiral character, despite its great importance in the pharmaceutical industry, has been overlooked by environmental researchers.

More than half of the drugs currently in use are chiral compounds and many of those are distributed as racemates consisting of an equimolar mixture of two enantiomers. Enantiomers of the same drug have the same chemical formula and physicochemical properties but they differ in interactions with chiral environments such as enzymes. Therefore in biological systems they have to be recognised as two different substances that elicit different responses: one enantiomer of the same drug may produce the desired therapeutic activity, while the other may be inactive or even toxic. The ratio of active/inactive enantiomer of the chiral drug can change significantly after its administration, metabolism in and excretion from the body. It can be subsequently altered during wastewater treatment and when the drug is already present in the environment. This is because degradation of enantiomers can be stereo-specific and can in some cases lead to an increase in the drug's toxicity. As a result chiral PACs might reveal different environmental persistence, fate and toxicity. Currently, the environmental fate and toxicity of chiral drugs are assessed without taking into consideration their enantiomeric form. This might lead to a significant under or overestimation of toxicity of chiral drugs and to inaccurate environmental risk assessment.

As a consequence there is an urgent need to identify chiral drugs, which are resistant to currently used wastewater treatment technologies, are characterised by stereoselective degradation during wastewater treatment and can as a result be released into the environment or remain in reclaimed water in the form of non-racemic mixtures. This project will tackle this issue as it aims to test the hypothesis that degradation of chiral drugs during wastewater treatment and in receiving waters is stereoselective and will be undertaken at the laboratory scale with the usage of microcosm protocol and in a full scale wastewater treatment plant.

This research project has the potential to provide significant advances in understanding of the mechanisms of the distribution and fate of chiral drugs during wastewater treatment and in receiving waters and open up a new area of research directed at the stereoselective behaviour of drugs in the environment. It will also be of vital importance for the verification of risks associated with water reclamation

The proposed research, due to its innovative and multidisciplinary nature has the potential to benefit a wide range of user groups:
1. The scientific community
This project will significantly advance knowledge and raise awareness of the importance of the phenomenon of chirality of drugs in the areas of water technology, ecotoxicity of drugs and their impact on the environment and human health. The outcomes of the project will be of vital importance to those researching into (waste)water treatment processes, water reuse and drinking water quality as it will provide an assessment of treatment technologies for the removal of chiral drugs and will give an indication of whether wastewater is sufficiently treated before it is released into receiving waters or is reclaimed for potable use. Environmental scientists with interests in environmental pollution will benefit considerably from the project as it will assess the impact a discharge of insufficiently treated wastewater can have on the aquatic environment. An understanding of the stereoselective pathways of microbial degradation of chiral drugs during wastewater treatment will give invaluable information about possible changes in overall toxicity of chiral drugs and therefore will be vital to ecotoxicologists.
2. Policy makers and government agencies
This research will provide an assessment of the efficiency of wastewater treatment in the context of stereoselective removal of chiral drugs and will break new ground in adding to the current body of knowledge. In the light of the research, statutory agencies and legislators such as DEFRA and Environment Agency will be in a better position to make judgments regarding the restriction of specific pharmaceuticals which may negatively impact on human health and the environment. There may be grounds for legislative, procedural or policy changes in the area of wastewater treatment which are likely to be of significant interest to regulators at an European and international level. This would include the European Commission and Parliament and WHO.
3. Commercial/private sector
The research will focus on the degradation of chiral drugs during wastewater treatment, and therefore will provide a valuable insight into key processes of interest to those working in water industry. Through estimation of process efficiency, the research will also provide environmental scientists in the commercial sector with a better understanding of the impact of wastewater treatment on the state of the environment. It should also indicate the necessity of new technological development to enhance existing treatment processes. The development of an analytical methodology will also be of use to the commercial sector including environmental and forensic scientists as well as pharmacists.
4. The general public
Water is a limited resource in an expanding global economy and population. In the future its accessibility will be significantly impacted by changing climate. As a consequence, reclaiming water for (non-)potable purposes is considered to be an important element of sustainable water resource management. There are, however, certain risks associated with water reuse including microbiological and chemical risks (e.g. the presence of drugs in reclaimed water). These have to be verified before water reuse is to be implemented on a wider scale. Through dissemination of the outcomes via appropriate media channels this research will enhance public knowledge of key water quality and environmental concerns and priorities for future research and monitoring activity.
5. Other
Finally, the research project will further develop expertise in environmental chemistry at the University of Bath through collaboration with other research staff to meet project objectives. A PhD student working on this project will benefit from acquiring expertise in a multidisciplinary field of water science including analytical and environmental science and water technolology.