title: Applying quantitative structure-activity relationship (QSAR) methodology for modeling postmortem redistribution of benzodiazepines and tricyclic antidepressants.
abstract: Postmortem redistribution (PMR) constitutes a multifaceted process, which complicates the interpretation of drug concentrations by forensic toxicologists. The present study aimed to apply quantitative structure-activity relationship (QSAR) analysis for modeling PMR data of structurally related drugs, 10 benzodiazepines and 10 tricyclic antidepressants. For benzodiazepines, an adequate QSAR model was obtained (R(2) = 0.98, Q(2) = 0.88, RMSEE = 0.12), in which energy, ionization and molecular size exerted significant impact. For tricyclic antidepressants, an adequate QSAR model with slightly inferior statistics (R(2) = 0.95, Q(2) = 0.87, RMSEE = 0.29) was established after exclusion of maprotiline, in which energy parameters, basicity character and lipophilicity exerted significant contribution. Thus, QSAR analysis could be used as a complementary tool to provide an informative illustration of the contributing molecular, physicochemical and structural properties in PMR process. However, the complexity, non-static and time-dependent nature of PMR endpoints raises serious concerns whether QSAR methodology could predict the degree of redistribution, highlighting the need for animal-derived PMR data.
authors.affiliation: 1Department of Food Science and Nutrition, School of Environment, University of the Aegean, Mitropoliti Ioakeim 2 Street, Myrina, Lemnos GR 81400, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Giaginis
authors.forename: Anna
authors.initials: A
authors.lastname: Tsantili-Kakoulidou
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
mesh_terms: D000929:Antidepressive Agents, Tricyclic / Q000032:analysis* / Q000378:metabolism; D001569:Benzodiazepines / Q000032:analysis* / Q000378:metabolism; D053593:Forensic Toxicology; D006801:Humans; D008954:Models, Biological; D011180:Postmortem Changes; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000929:Antidepressive Agents, Tricyclic; D001569:Benzodiazepines