Abstract: AimTo investigate the interaction between drugs and ordered phospholipid membrane using immobilized artificial membrane chromatography (IAMC). MethodsIAMC was used to determine the interaction drugs with phospholipid membrane, expressed as membrane affinity (lg K_IAM). An n-octanol/buffer system was also employed as the reference hydrophobicity (lg DO/W,7.4). ResultsWithin the range of used acetonitrile percentages (φ) 0～30% in mobile phase, retention index (lg K′_IAM) showed excellent correlation with φ. Intercepts of fitted straight lines between lg K′_IAM and φ were comparable but slopes were much different for the three organic modifiers (acetonitrile, ethanol and methanol). Effects by adding CH₂ substituent on lipophilicity difference (Δlg K_IAM and Δlg DO/W,7.4) were similar for P-hydroxyl benzoic methyl ester to butyl ester, whereas different for P-hydroxylbenzoic acid to methyl ester. ConclusionIAMC system is a convenient, efficient and rapid tool for determining membrane interaction.