Rapid screening of blood-brain barrier penetration of drugs using the immobilized artificial membrane phosphatidylcholine column chromatography

Abstract

The chromatographic capacity factors (k(IAM)) of 23 structurally diverse drugs were measured by the immobilized artificial membrane (IAM) phosphatidylcholine chromatography for the prediction of blood-brain barrier (131313) penetration. The k(IAM), was determined using the mobile phase consisting of acetonitrile:DPBS (20:80 v/v) and corrected for die molar volume of the solutes (k(IAM)/MWn). The con-elation between k(IAM)/MWn and CNS penetration was highest when measured at pH 5.5 with the power function of n = 4. This in vitro prediction method was validated with 7 newly synthesized PDE-4 inhibitors. The relationship between in vivo plasma-to-brain concentration ratios and in vitro CNS penetration was excellent (r = 0.959). The developed in vitro prediction method may be used as a rapid screening tool for 131313 penetration of drugs with passive transport mechanism, with high success, low cost, and reproducibility.