Advanced LC-analysis of human plasma for metallodrug metabolites

Publication date: September 2015 Source:Drug Discovery Today: Technologies, Volume 16 Author(s): Melani Sooriyaarachchi, Thomas T. Morris, Jürgen Gailer Understanding the fate of metallodrugs in the bloodstream is critical to assess if the parent drug has a reasonable probability to reach the intended target tissue and to predict toxic side-effects. To gain insight into these processes, we have added pharmacologically relevant doses of metallodrugs to blood plasma and applied an LC-method to directly analyze the latter for metallodrug metabolites. Using human or rabbit plasma, this LC-method was employed to gain insight into the metabolism of clinically used as well as emerging anticancer metallodrugs and to unravel the mechanisms by which small molecular weight compounds that – when co-administered with a metallodrug – decrease the toxic side-effects of the metallodrug by modulating its metabolism. The results suggest that the developed LC-method is useful to probe the fate of biologically active novel metal-complexes in plasma to help select those which may be advanced to animal/clinical studies to ultimately develop safer metallodrugs. Graphical abstract
Source: Drug Discovery Today: Technologies - Category: Drugs & Pharmacology Source Type: research