title: Evaluation of sphingomyelin, cholester, and phosphatidylcholine-based immobilized artificial membrane liquid chromatography to predict drug penetration across the blood-brain barrier.
abstract: Over the past decades, several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier. So far, in high-performance liquid chromatography, most attention has been paid to micellar liquid chromatography and immobilized artificial membrane (IAM) LC. IAMLC has been described as a viable approach, since the stationary phase emulates the lipid environment of a cell membrane. However, research in IAMLC has almost exclusively been limited to phosphatidylcholine (PC)-based stationary phases, even though PC is only one of the lipids present in cell membranes. In this article, sphingomyelin and cholester stationary phases have been tested for the first time towards their ability to predict drug penetration across the blood-brain barrier. Upon comparison with the PC stationary phase, the sphingomyelin- and cholester-based columns depict similar predictive performance. Combining data from the different stationary phases did not lead to improvements of the models.
authors.affiliation: Separation Science Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4bis, 9000, Ghent, Belgium.
authors.forename: Mike
authors.initials: M
authors.lastname: De Vrieze
authors.forename: Dieter
authors.initials: D
authors.lastname: Verzele
authors.forename: Roman
authors.initials: R
authors.lastname: Szucs
authors.forename: Pat
authors.initials: P
authors.lastname: Sandra
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lynen
mesh_terms: D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000737:chemistry* / Q000378:metabolism; D002783:Cholestenones / Q000737:chemistry* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007700:Kinetics; D008567:Membranes, Artificial; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010599:Pharmacokinetics; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D013109:Sphingomyelins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002783:Cholestenones; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D013109:Sphingomyelins