LC/electrochemistry/mass spectrometry in (bio)analytical chemistry, drug metabolism and proteomics
Final Report Abstract
This project has focused on the development of new methods for the on-line investigation of electrogenerated products. The development of a fully automated method for unattended recording of mass voltammograms (mass spectra recorded in dependency of the applied potential) is an important step to transfer EC/MS into an approach that may find larger use in academia and industry. Another important aspect is a new approach for differential protein labelling based on electrogenerated stable isotope labels. This has been shown to be applicable for several proteins of physiological significance. Quantification of electrogenerated species is another important issue, and in this project, it has been shown that they can be quantified by electrochemistry coupled to liquid chromatography and ICP-MS, while using a countergradient to eliminate signal deviations due to different solvent composition. This was demonstrated for the quantification of thyroid hormones. The reductive electrochemical activation of platinum(IV) complexes to the respective platinum(II)-based cytostatics has also been investigated successfully within this project. Finally, trapped ion mobility spectrometry has been implemented as a new, extremely fast way to separate electrogenerated compounds of interest prior to mass spectrometric analysis.
Publications
- Comparison of in silico, electrochemical, in vitro and in vivo metabolism of a homologous series of (radio)fluorinated sigma(1) receptor ligands designed for positron emission tomography. ChemMedChem 11 2445-2458 (2016)
Wiese, C.; Grosse Maestrup, E.; Galla, F.; Schepmann, D.; Hiller, A.; Fischer, S.; Ludwig, F.-A.; Deuther-Conrad, W.; Donat, C.K.; Brust, P.; Büter, L.; Karst, U.; Wünsch, B.
(See online at https://doi.org/10.1002/cmdc.201600366) - Structure elucidation and quantification of the reduction products of anticancer Pt(IV) prodrugs by electrochemistry/mass spectrometry (EC/MS). Analyst 143 1997-2001 (2018)
Frensemeier, L.M.; Mayr, J.; Koellensperger, G.; Keppler, B.K.; Kowol, C.R.; Karst, U.
(See online at https://doi.org/10.1039/c8an00258d) - Fast online separation and identification of electrochemically generated isomeric oxidation products by trapped ion mobility-mass spectrometry. Anal. Chem. 92 1205-1210 (2020)
Fangmeyer, J.; Scheeren, S.G.; Schmid, R.; Karst, U.
(See online at https://doi.org/10.1021/acs.analchem.9b04337)
