In Vitro modeling of angiotensin-converting enzyme inhibitor's absorption with chromatographic retention data and selected molecular descriptors

•In Vitro modeling of ACE inhibitor's absorption by MLR analysis.•MLR analysis with hydrophobicity data and selected molecular descriptors.•Retention data were obtained by SOTLC as environmentally friendly technique.•The selection of topological polar surface area as independent variable.•Proposed model checking with zofenopril, trandolapril and captoril.

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 (RM0 or C0) obtained by ascending technique applying four different salts, (NH4)2SO4, NH4NO3, NH4Cl and NaCl as mobile phases. The best correlations between KOWWIN log P   and both hydrophobicity parameters, RM0 and C0, (R2 > 0.850) were observed for NaCl (1.0–3.0 M) while the lowest R2 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 R2 = 0.823 for RM0 or R2 = 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.

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