title: In vitro modeling of angiotensin-converting enzyme inhibitor's absorption with chromatographic retention data and selected molecular descriptors.
abstract: Set of nine angiotensin-converting enzyme inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, benazepril, perindopril and moexipril) were studied to evaluate the correlation between their intestinal absorption and salting-out thin-layer chromatography hydrophobicity parameters (RM(0) or C0) obtained by ascending technique applying four different salts, (NH4)2SO4, NH4NO3, NH4Cl and NaCl as mobile phases. The best correlations between KOWWIN logP and both hydrophobicity parameters, RM(0) and C0, (R(2)>0.850) were observed for NaCl (1.0-3.0M) while the lowest R(2) was obtained for (NH4)2SO4 (0.649 and 0.427, respectively) due to highest salting-out effect of (NH4)2SO4. The effect of selected inorganic salts in the salting-out mobile phases, on the solutes solubility and retention was evaluated. The topological polar surface area should be selected as independent variable (only this molecular descriptor showed low correlation with chromatographic hydrophobicity parameters) for multiple linear regression analysis, to obtain reliable correlation between angiotensin-converting enzyme inhibitor's intestinal absorption data and salting-out thin-layer chromatograpic hydrophobicity parameters. These correlations provide R(2)=0.823 for RM(0) or R(2)=0.799 for C0 indicating good relationship between predicted and literature available intestinal absorption (ranged from 22% to 70%) of investigated angiotensin-converting enzyme inhibitors. The proposed in vitro model was checked with three in addition experimentally analyzed drugs, zofenopril, trandolapril and captoril. The satisfactory absorption prediction was obtained for zofenopril and trandolapril, while divergence established for captopril resulted from considerably different structure.
authors.affiliation: Department of Analytical Chemistry, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: jodovic@pharmacy.bg.ac.rs.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Odović
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Marković
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Sote
authors.initials: S
authors.lastname: Vladimirov
authors.affiliation: Department of Analytical Chemistry, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: kkrajic@pharmacy.bg.ac.rs.
authors.forename: Katarina
authors.initials: K
authors.lastname: Karljiković-Rajić
mesh_terms: D000042:Absorption; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D002855:Chromatography, Thin Layer / Q000379:methods*; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D012492:Salts
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012492:Salts
keywords: Absorption modeling; Angiotensin-converting enzyme inhibitors; Lipophilicity; Salting-out thin-layer chromatography