title: Advanced LC-analysis of human plasma for metallodrug metabolites.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada.
authors.forename: Melani
authors.initials: M
authors.lastname: Sooriyaarachchi
authors.affiliation: Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Morris
authors.affiliation: Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada. Electronic address: jgailer@ucalgary.ca.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gailer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D056831:Coordination Complexes / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D011817:Rabbits
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes