Immobilized-artificial-membrane chromatography: Measurements of membrane partition coefficient and predicting drug membrane permeability

Immobilized artificial membranes (IAMs) are chromatographic surfaces prepared by covalently immobilizing cell membrane phospholipids to solid surfaces at monolayer densities. IAM surfaces mimic fluid cell membranes. For 23 structurally unrelated compounds, solute capacity factors [log (k'(IAM))] measured on IAM columns correlate very well with the solute equilibrium partition coefficients [log (K-m)] measured in fluid liposome systems (r = 0.907), This indicates that solute partitioning between the IAM bonded phase and the aqueous mobile phase is similar to the solute partitioning between liposomes and the aqueous phase. IAMs also predicted oral drug absorption in mice and drug permeability through Caco-2 cells. IAM chromatography is experimentally simple and large volume screening of experimental compounds for drug absorption is possible. Solute retention on IAMs was found to be dominated by a partitioning mechanism. The structural requirements for HPLC bonded phases to predict solute-membrane partitioning are briefly discussed.