title: Evaluation of angiotensin-converting enzyme inhibitor's absorption with retention data of micellar thin-layer chromatography and suitable molecular descriptor.
abstract: Twelve angiotensin-converting enzyme (ACE) inhibitors were studied to evaluate correlation between their absorption (ABS) data available in the literature (22-96%) and hydrophobicity parameters (km and Pm/w) obtained in micellar thin-layer chromatography (MTLC) using Brij 35. The theoretical considerations showed that the geometric molecular descriptor-volume value (Vol) should be considered as an independent variable simultaneously with calculated hydrophobicity parameters in multiple linear regression analysis to obtain reliable correlation between ACE inhibitor's absorption and lipophilicity (calculated KOWWINlog P) and that captopril should be excluded from further correlations. The results of MTLC confirmed that between the two hydrophobicity parameters km and Pm/w, for absorption prediction of 11 ACE inhibitors, the micelle-water partition coefficient Pm/w provided higher correlation (R(2) = 0.756), while for the km parameter R(2) = 0.612 was obtained. The micelle-water partition coefficient Pm/w could be considered as analogous to hydrophobicity parameter C0 from reversed-phase thin-layer chromatography. Dissimilar retention behavior of lisinopril indicated its lowest non-polar interaction with micelle, because of its di-acid form. The proposed model which included ACE inhibitors on the opposite site of lipophilicity-lisinopril and fosinopril (KOWWINlog P = -0.96 and KOWWINlog P = 6.61, respectively), both with similar absorption values (25 and 36%, respectively), could indicate that absorption of investigated compounds occurs via two different mechanisms: active and passive transport.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade 11221, Serbia jodovic@pharmacy.bg.ac.rs.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Odovic
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade 11221, Serbia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Markovic
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade 11221, Serbia.
authors.forename: Sote
authors.initials: S
authors.lastname: Vladimirov
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade 11221, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Karljikovic-Rajic
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002855:Chromatography, Thin Layer / Q000379:methods*; D008823:Micelles
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D008823:Micelles