The aim of the study was to investigate the immobilized artificial membrane (IAM) retention mechanism for a set of flavonoids and to evaluate the potential of IAM chromatography to model Caco-2 permeability. For this purpose, the retention behavior of 41 flavonoid analogs on two IAM stationary phases, IAM.PC.MG and IAM.PC.DD2, was investigated. Correlations between retention factors, logkw(IAM) and octanol-water partitioning (logP) were established and the role of hydroxyl groups of flavonoids to the underlying retention mechanism was explored. IAM retention and logP values were used to establish sound linear models with Caco-2 permeability (logPapp ) taken from the literature. Both stepwise regression and multivariate analysis confirmed the contribution of hydrogen bond descriptors, as additional parameters in the either logkw(IAM) or logP models. Retention factors on both IAM stationary phases showed comparable performance with n-octanol-water partitioning towards Caco-2 permeability.
Keywords: Caco-2 permeability assay; flavonoids; immobilized artificial membrane (IAM) chromatography; intestinal permeability; lipophilicity; phospholipophilicity.
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