IMMOBILIZED ARTIFICIAL MEMBRANE CHROMATOGRAPHY: A USEFUL TOOL FOR PREDICTING MEMBRANE PERMEABILITY
Ahmed El Gendy* and Adeboye Adejare*
The potential of immobilized artificial membrane (IAM) chromatography to predict intestinal and blood brain barrier (BBB) permeability was investigated utilizing retention indices and other permeability factors compiled from literatures such as the lipophilicity factor, logarithms of octanol/water partition coefficient (log P) and blood/brain partition coefficient (log BB). For this purpose, the separation of a diverse structures and functions set of 21 compounds was studied on stationary immobilized artificial membrane and their chromatographic retention factors; namely aqueous capacity factor (log KIAMW) were determined. The aqueous capacity factors of the compounds were correlated with their log P and log BB. Linear correlation was obtained between log KIAMW and log P of the compounds (r > 0.95). Log KIAMW values of the compounds also showed an acceptable correlation with log BB (r > 0.76). Inclusion of the molecular size of the compounds with log KIAMW data had negative effect on correlations when the data plotted vs. log BB values. For a subset of 8 compounds, log KIAMW showed better correlation with log % of human absorption than did log P. These results show that the aqueous capacity factor, log KIAMW seems to provide a valuable assessment of drug permeability through biological membranes.
Keywords: IAM Chromatography; log KIAMW, intestinal permeability; blood brain barrier permeability.
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