Name: Daniel Melles
Diploma / M.Sc degree: Westfälische Wilhelms-Universität Münster, Germany
(November 2010)

PhD Project: Simulation of the oxidative degradation of skin sensitizers by coupling of electrochemistry, liquid chromatography and mass spectrometry

Abstract of Research Project

A secure use of pharmaceutical and cosmetic substances requires the investigation of metabolic stability and resulting interactions. Generally, these studies are conducted in ethically questionable in vivo or in vitro experiments. Regarding possible skin sensitizers and their use in cosmetics, the search for alternatives is of special interest, since animal tests for substances in cosmetic use are banned from 2013 according to European Commission regulation No 1223/2009.

Therefore, the application of a purely instrumental approach may provide a part of the solution to this problem. As metabolic reactions usually go along with the oxidation of the parent substance in the first place, electrochemistry is able to mimick most of these oxidation reactions. Resulting products are then characterized by mass spectrometry. Furthermore, adverse effects related to these oxidation products are mostly a result of their attack to molecules, which are inherent to the body. In particular, skin sensitization is a process, which is initiated by the modification of skin proteins, normally by an oxidized and therefore activated agent. Thus, trapping experiments are a significant part of this work. After the electrochemical oxidation, the products are trapped by selected agents such glutathione, proteins or model peptides. Subsequent adducts are analyzed by liquid chromatography and mass spectrometry. Hereby, the reactivity of the oxidation product can be assessed and potential adverse reactions are clarified.

The electrochemical approach does not only offer the opportunity of a complete non animal investigation, but it also provides the opportunity to synthesize oxidative metabolites, which are difficult to prepare by alternative methods.



Publications

D. Melles, T. Vielhaber, A. Baumann, R. Zazzeroni, U. Karst
In chemico evaluation of skin metabolism: Investigation of eugenol and isoeugenol by electrochemistry coupled to liquid chromatography and mass spectrometry
J. Chromatogr. B 913– 914 (2013), 106–112.

D. Melles, T. Vielhaber, A. Baumann, R. Zazzeroni, U. Karst
Electrochemical oxidation and protein adduct formation of aniline: a liquid chromatography/mass spectrometry study
Anal. Bioanal. Chem., 403(2) (2012), 377-384.