Analysing toxicity of ionic liquids based on combined targeted amino acid analysis and untargeted metabolic profiling as well as lipidomic profiling of stressed mammalian cell extracts

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Dokumentart: Dissertation
Date: 2023-04-30
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Pharmazie
Advisor: Lämmerhofer, Michael (Prof. Dr.)
Day of Oral Examination: 2021-04-30
License: Publishing license excluding print on demand
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Ionic Liquids are characterised by their modifiable unique properties and are used today in many different industrial processes. Their composition similar to a salt consists of an organic cation and an organic or inorganic anion. The large number of cations and anions, that can be combined with each other, makes a detailed characterisation difficult, especially with regard to their toxic effects on the environment. For this reason, a rapid analytical method was developed in the present work, which determines the toxicity of various ionic liquids based on their half maximal effective concentration (EC50) and analyses their effect on the environment. The initial focus was placed on the development of a targeted analysis of amino acids of a cell extract after exposure to ionic liquids, as they are very important metabolites of an organism. The use of hydrophilic interaction liquid chromatography (HILIC) coupled to a quadrupole time-of-flight mass spectrometer (QTOF) and the data-independent SWATH acquisition method (sequential window acquisition of all theoretical fragment-ion spectra) enabled the combination of a targeted amino acid analysis with an untargeted analysis of all other metabolites. The analysis of the cell extracts after exposure to the ionic liquids showed that the concentration profiles are strongly dependent on the toxicity or EC50 value of the respective ionic liquid. Already during the EC50 determination, it turned out that some ionic liquids trigger the cells to build lipid droplets as a reaction. Therefore, the last project of the present work dealt with the analysis of the lipidome (lipidomics) of a cell after exposure to ionic liquids. Finally, the ionic liquid-mixed cell extracts were compared with untreated cell extracts (control) for first hypotheses generation. It could be shown in this work that metabolomics and lipidomics profiling methods are suitable means to obtain information about the potential toxicity of ionic liquids, possibly also giving some insight which metabolic subnetworks are involved in toxic effects. It is becoming an established powerful tool in the field of exposomics.

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