High-throughput lipophilicity measurement with immobilized artificial membranes.
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.
Faller
Bernard
B
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
Grimm
Hans Peter
HP
Loeuillet-Ritzler
Frédérique
F
Arnold
Sabine
S
Briand
Xavier
X
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
D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D014867:Water; D020003:1-Octanol