title: High-throughput lipophilicity measurement with immobilized artificial membranes.
abstract: We report on a new, high-throughput assay designed to measure octanol/water partition coefficients in early drug discovery. The assay is carried out in 96-well microtiterplates and measures the diffusion of compounds between two aqueous compartments separated by a thin octanol liquid layer. Octanol/water partition coefficients are derived from the apparent permeability (P(a)) values using a calibration curve. The assay can measure partition coefficients within the range -2 to + 8; thus, a dynamic range of 10 log units can be covered in one single run. Unlike chromatographic methods, the technology is not restricted to neutral and weakly basic compounds, and, as no stationary phase is involved, the data can be strictly compared with values obtained from traditional methods such as shake-flask/HPLC or dual-phase potentiometric titration.
authors.affiliation: Novartis Institutes for BioMedical Research, WSJ-350.3.04, CH-4002 Basel, and GiMS mbH, Maulbeerstrasse 44, CH-4058 Basel. bernard.faller@pharma.novartis.com
authors.forename: Bernard
authors.initials: B
authors.lastname: Faller
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Grimm
authors.forename: Frédérique
authors.initials: F
authors.lastname: Loeuillet-Ritzler
authors.forename: Sabine
authors.initials: S
authors.lastname: Arnold
authors.forename: Xavier
authors.initials: X
authors.lastname: Briand
mesh_terms: D020003:1-Octanol; D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D015195:Drug Design; D007700:Kinetics; D008567:Membranes, Artificial; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D016062:Porosity; D013329:Structure-Activity Relationship; D014867:Water
chemical_list: D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D014867:Water; D020003:1-Octanol