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 phosphatidylcholine's 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 logK(mbm) values were correlationed with the absorbed fraction of drugs orally administered in humans (%F(a)) and a hyperbolic relationship was obtained. Meanwhile, the relationship between the logK(mbm) values and hydrophobic parameters (logP(oct) and logD(oct)) 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 logK(mbm) values have good relationship with logK(W)(IAM), logK(BMC) and have moderate to fair relationship with logK(s) determined on four different ILC column (EPL, PC, PC-PE, PC-PS). Therefore, the logK(mbm) 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.
Hu
Zhi-Xiong
ZX
Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Zhang
Wei-Nong
WN
He
Hai-Bo
HB
Feng
Yu-Qi
YQ
Da
Shi-Lu
SL
D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008277:Magnesium Oxide / Q000737:chemistry; D008567:Membranes, Artificial; D010599:Pharmacokinetics; D015203:Reproducibility of Results; D015040:Zirconium / Q000737:chemistry
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D008277:Magnesium Oxide; D015040:Zirconium; C028541:zirconium oxide