title: Predicting drug penetration across the blood-brain barrier: comparison of micellar liquid chromatography and immobilized artificial membrane liquid chromatography.
abstract: Several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier (BBB) into the central nervous system (CNS). In this article, the performance of a variety of micellar liquid chromatographic (MLC) methods and immobilized artificial membrane (IAM) liquid chromatographic approaches were compared for a set of 45 solutes. MLC measurements were performed on a C18 column with sodium dodecyl sulfate (SDS), polyoxyethylene (23) lauryl ether (Brij35), or sodium deoxycholate (SDC) as surfactant in the micellar mobile phase. IAM liquid chromatography measurements were performed with Dulbecco's phosphate-buffered saline (DPBS) and methanol as organic modifier in the mobile phase. The corresponding retention and computed descriptor data for each solute were used for construction of models to predict transport across the blood-brain barrier (log BB). All data were correlated with experimental log BB values and the relative performance of the models was studied. SDS-based models proved most suitable for prediction of log BB values, followed closely by a simplified IAM method, in which it could be observed that extrapolation of retention data to 0% modifier in the mobile phase was unnecessary.
authors.affiliation: Separation Science Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4bis, 9000, Ghent, Belgium.
authors.forename: Mike
authors.initials: M
authors.lastname: De Vrieze
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lynen
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Roman
authors.initials: R
authors.lastname: Szucs
authors.forename: Pat
authors.initials: P
authors.lastname: Sandra
mesh_terms: D001812:Blood-Brain Barrier; D002021:Buffers; D002853:Chromatography, Liquid / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D016018:Least-Squares Analysis; D008567:Membranes, Artificial; D008823:Micelles; D008962:Models, Theoretical; D000069437:Pharmacological Phenomena; D011092:Polyethylene Glycols / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate; D012984:Software; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D002021:Buffers; D008567:Membranes, Artificial; D008823:Micelles; D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols