Magnesia–zirconia based mimetic biomembrane chromatography for predicting human drug absorption

In this paper, a novel mimetic biomembrane chromatography stationary phase of magnesia–zirconia composite matrix were prepared with the Lewis acid–base interaction between phosphatidylcholineʹs residue phosphonate group and Lewis acid sites of magnesia–zirconia composite; the retention factors of a chemically diverse set of drugs on the new stationary phase were determined; the drugs log Kmbm values were correlationed with the absorbed fraction of drugs orally administered in humans (%Fa) and a hyperbolic relationship was obtained. Meanwhile, the relationship between the log Kmbm values and hydrophobic parameters (log Poct and log Doct) were discussed. The usefulness of the new column for predicting oral drug absorption in humans is demonstrated by comparing this model with IAM, ILC and BMC models. Results show that the log Kmbm values have good relationship with log K W IAM , log KBMC and have moderate to fair relationship with log Ks determined on four different ILC column (EPL, PC, PC-PE, PC-PS). Therefore, the log Kmbm values can provide key information about the transport properties of drugs and this chromatographic model may be applicable for prediction of drug uptake through epithelial cell membranes during the drug discovery process.