title: Analytical tools for the physicochemical profiling of drug candidates to predict absorption/distribution.
abstract: The measurement of physicochemical properties at an early phase of drug discovery and development is crucial to reduce attrition rates due to poor biopharmaceutical properties. Among these properties, ionization, lipophilicity, solubility and permeability are mandatory to predict the pharmacokinetic behavior of NCEs (new chemical entities). Due to the high number of NCEs, the analytical tools used to measure these properties are automated and progressively adapted to high-throughput technologies. The present review is dedicated to experimental methods applied in the early drug discovery process for the determination of solubility, ionization constants, lipophilicity and permeability of small molecules. The principles and experimental conditions of the different methods are described, and important enhancements in terms of throughput are highlighted.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai E-Ansermet 30, 1211, Geneva 4, Switzerland.
authors.forename: Yveline
authors.initials: Y
authors.lastname: Henchoz
authors.forename: Bruno
authors.initials: B
authors.lastname: Bard
authors.forename: Davy
authors.initials: D
authors.lastname: Guillarme
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Veuthey
authors.forename: Sophie
authors.initials: S
authors.lastname: Martel
mesh_terms: D002853:Chromatography, Liquid; D015195:Drug Design; D055808:Drug Discovery; D008055:Lipids / Q000737:chemistry; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*; D010599:Pharmacokinetics; D012995:Solubility
chemical_list: D008055:Lipids; D004364:Pharmaceutical Preparations