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Comprehensive information package – 4 publications on reactive metabolites

17 March 2016

During the last year our team members have contributed in 4 high-quality peer-reviewed scientific articles on chemically reactive drug metabolites. The first article focuses on investigating the applicability of biomimetic metalloporphyrin catalysts for producing and further glutathione trapping of reactive metabolites, and it was observed that in selected cases the production of GSH-conjugates was on the scale relevant for purification and subsequent identification by NMR. In the second article various in vitro liver derived subcellular and cellular incubation systems were com pared for the formation of GSH-trapped reactive metabolites. Based on the test set of 10 compounds significant differences were observed between cell based and subcellular assays, as HepaRG cells and hepatocytes produced clearly lower number and lower abundances of GSH-conjugates. Hence the different enzyme systems are only comparable qualitatively.

The role of acyl migration and CoA conjugation to toxicity of carboxylic acid-containing drugs was examined in the third article. As an outcome, the high acyl migration rate, high daily dose of the drug and detection of acyl CoA conjugates or any further metabolites from CoA, were found to correlate with DILI, while neither cytotoxicity nor mitochondrial toxicity were showing any correlation. The fourth and latest paper utilised menthofuran as an example to provide information for setting up LC/MS/MS method for detecting both N-linked and S-linked GSH-conjugates.

These articles make a great addition to our list of peer-reviewed scientific papers. Please contact us how the new information can be applied to advance your research project!

Admescope welcomes a new team member

Admescope continues solid growth! We are happy to welcome Toni Lassila as a research scientist to our team. Toni is a talented chemist and the main author in all four above mentioned reactive metabolite publications. He will shortly defend his doctorate thesis, co-supervised by Admescope and University of Oulu, Chemistry Department. Welcome Toni!