Projects / Programmes
Development of Molecularly Imprinted Polymers and their application in environmental and bio-analysis
| Code |
Science |
Field |
Subfield |
| 1.08.00 |
Natural sciences and mathematics |
Control and care of the environment |
|
| Code |
Science |
Field |
| P305 |
Natural sciences and mathematics |
Environmental chemistry |
| Code |
Science |
Field |
| 1.05 |
Natural Sciences |
Earth and related Environmental sciences |
Molecularly Imprinted Polymers; pharmaceuticals; transformation products; metabolites; environment; biological samples; solid phase extraction;
Researchers (18)
Organisations (4)
Abstract
The proposed project aims to investigate the occurrence and fate of pharmaceutical residues, defined as parent compounds, metabolites and transformation products (TPs) in the aqueous environment. In contrast with parent pharmaceuticals and metabolites, TPs formed during water treatment and environmental breakdown are mainly unknowns with little published data concerning their fate and effects on humans and other living organisms. Since the quantitative analysis of pharmaceuticals in complex matrices is limited to a group of predetermined analytes, TPs are often overlooked, and as they occur in trace levels, the analytical method sensitivity is often insufficient to detect them.
This project will overcome these limitations by using novel Molecularly Imprinted sorbents for Solid Phase Extraction (MISPE sorbents) to improve determination of pharmaceutical residues in complex matrices. Fundamentally, the cross-selectivity provided by MISPE sorbents will be exploited for extraction of structurally related compounds, specifically pharmaceutical residues, which goes beyond what is possible using the state-of-the-art analytical methods.
The project will investigate two groups of pharmaceutical residues, which were in our previous research recognised as important environmental microcontaminants: benzodiazepine tranquilizers (e.g. diazepam, oxazepam, bromazepam) and capecitabine. Benzodiazepine tranquilizers pose a threat to the environment due to their high consumption, environmental persistence and proved toxic effect on aquatic organisms. Capecitabine is the active substance in an oral anticancer drug, which is during metabolism transformed into cytotoxic, genotoxic and mutagenic fluorouracil and into several other TPs, which may show similar effects in the aqueous environment. Having developed the MISPE sorbents with good recognition for benzodiazepine or capecitabine residues in aqueous matrices our findings will not remain limited to the environmental analysis (waste- and surface waters), but will be during the course of the project extended to bioanalysis. For this purpose, plasma, faeces and tumour samples (in case of capecitabine), or liver and brain (in case of benzodiazepines) of test animals that have been administered the selected pharmaceutical will be screened for the parent pharmaceuticals and their metabolites. Finally, to broaden the impact of the project results and to demonstrate its interdisciplinarity, the developed MISPE sorbents will be investigated for the following applications: (i) assessment of the environmental occurrence of pharmaceutical residues, (ii) solid phase microextraction, and (iii) passive sampling. These breakthrough achievements will open new horizons in understanding the risks that pharmaceutical residues pose to the environment and human health, and will reveal the applicability of MISPE sorbents beyond the environmental analysis, e.g. in environmental technologies, forensics, pharmacy and food technology.
Significance for science
The project is based on the fact that today a lot of attention is devoted to the development of new selective and sensitive analytical methods that enable the extraction, isolation, purification and concentration of trace compounds from complex matrices. Aiming to increase the selectivity and sensitivity of the methods, molecularly imprinted polymers (MIPs) have been developed, which have potential applications in chromatography, catalysis, chemical sensors. Molecular Imprinted Solid Phase Extraction (MISPE) is considered one of the most promising MIP applications, either in the fields of environmental, clinical or food analysis. MISPE sorbents have been established among researchers, and even on the market, but in the framework of this project we tested their application, which has to our knowledge not yet been investigated. Namely, the active pharmaceutical substances are transformed into metabolites during the course of metabolism, as well as into transformation products (TPs) after they enter the environment. In contrast with the parent compounds and their metabolites, TPs are predominantly unknown compounds, having unexplained fate and effects on environmental organisms and humans. This is because the quantitative analysis of active substances in complex matrices is limited to a predefined group of target analytes and therefore it does not include TPs. This area is, to a certain extent, tackled by a "nontarget analysis", which is a state-of-the-art approach and is currently being implemented only in the best-equipped European laboratories for organic analysis. In this type of analysis, the composition of the sample is unknown, and the number of analytes is - in view of their number and source - unlimited, while an additional challenge represents the complexity of the sample matrix. Our goal was to limit the theoretically unlimited number of analytes treated by "nontarget analysis" using MISPE sorbents. The idea is that the current analytes, in this case the residues of the active pharmaceutical substances with an emphasis on metabolites and unknown TPs, can be isolated and concentrated from the complex sample in the sample preparation phase, and then analyzed using methodological approaches used in the nontarget analysis. As the result of the project we confirmed the fundamental research hypothesis: The properties of MISPE sorbents to selectively bind not only the target analyte, but also its structural analogues, can be exploited for simultaneous isolation of the parent compound, its metabolites and TPs. Below we list some examples where the project has fundamentally contributed to the development of science: - Development and implementation of nontarget analysis as the fundamental tool for detection, identification and monitoring of key risk parameters in the fields of food, health and the environment; - New scientific findings on which further development will be based in the field of applications of MIP technology; - Application of polymers in several fields, such as environmental technologies, environmental chemistry, medicine, forensics, etc., which significantly increased the applicability of MIPs and extended the impact of results.
Significance for the country
The most recognised impact of the project is in the field of environmental protection and consequently human wellbeing. Yet, the proposed research project is interdisciplinary and combines different research fields, including environmental analytical chemistry, organic and polymeric chemistry, and bioanalysis. Based on its interdisciplinarity the impacts in several fields can be expected, the most appealing are environment, health and forensics. The main impacts of the project are: A) Improved environmental quality control With development of novel tools for environmental quality assessment, we gained an integrated picture on the pollution of Slovene environment with selected pharmaceutical residues. We showed that wastewaters have a direct impact on surface water quality. This brings an improvement in comparison to previous environmental pollution studies and monitoring actions, which have been until now limited only to the parent compounds and possibly their metabolites. B) Application of MIPs in wastewater reuse The developed polymers are potentially useful for wastewater reuse, which represents a contribution to the circular economy, one of the strategic goals of development of Slovenia. C) Contribution of project results to the relevant EU policies/strategies By having chemical information on mixture composition of parent compounds, their metabolites and TPs, the grounds have been established for the toxicological characterisation and assessment of the risk related to the presence of pharmaceutical residues in the environment. In particular the results of the studies on combined exposure to the mixtures of pharmaceutical residues will render the overall assessment of their impact to human health and environment, and by disseminating these results the project is expected to contribute to the improvement of current EU legislative on environmental control, safety and mitigation strategies. D) Publicly available data for environmental risk assessment According to EMEA (Guideline on environmental risk assessment of medicinal products for human use, 2006), environmental risk should be assessed for all veterinary pharmaceuticals and new human medicinal products brought to the market since 2006. The valuable information on the environmental occurrence of TPs provided by this project will be available to the public to conduct the risk assessments for pharmaceutical residues in the environment. E) Improvement of pharmacotherapy in oncological patients The analytical method for the determination of bleomycin in serum and tumor samples, which was developed within the framework of this project, enabled the study of pharmacokinetics and thus the acquisition of data on the therapeutic window, the elimination rate and the half-life of this anticancer drug. Based on these data we proposed improvements in the course of treatment of head and neck cancer with electrochemotherapy aiming to improve the treatment efficiency and quality of life of the oncological patients.
Most important scientific results
Annual report
2014,
2015,
final report
Most important socioeconomically and culturally relevant results
Annual report
2014,
2015,
final report
