Generic fast gradient liquid chromatography/tandem mass spectrometry techniques for the assessment of the in vitro permeability across the blood-brain barrier in drug discovery.
Rapid, generic gradient liquid chromatography/tandem mass spectrometry (LC/MS/MS) assays, designed to accelerate sample analyses, have been developed to keep pace with the productivity of advanced synthetic procedures. In this study, LC/MS/MS was combined with an in vitro, cell-based, blood-brain barrier (BBB) model to evaluate the potential of new chemical entities (NCEs) to cross the BBB. This in vitro assay provides the permeability of discovery compounds across a monolayer of a primary culture of bovine brain microvessel endothelial cells in a fraction of the time that is required for in vivo studies (brain/plasma concentrations), using only 2 mg of the compound. The results are consistent with in vivo brain/plasma concentration ratio data.
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Inhou
I
Chu
Fei
F
Liu
Anthony
A
Soares
Pramila
P
Kumari
Amin A
AA
Nomeir
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002138:Calibration; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D013058:Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000378:metabolism*; D015203:Reproducibility of Results
D004364:Pharmaceutical Preparations