title: A method for measuring the lipophilicity of compounds in mixtures of 10.
abstract: Lipophilicity is an important parameter for any potential drug candidate. Accurate and efficient lipophilicity measurements facilitate the development of high-quality predictive in silico models that support the design of future drugs. Lipophilicity estimates derived from the traditional 1-octanol/water shake flask techniques have been the most widely employed and are therefore the best understood. This technique can be considered to give a good measure of a compound's lipophilicity, albeit slower and more labor intensive to run compared with some other methodologies. Herein is described and validated an efficient 1-octanol/water shake flask technique that has sufficient capacity to be run as a primary screen within the drug discovery process. This is achieved by the simultaneous measurement of the distribution coefficients of mixtures of up to 10 compounds using high-performance liquid chromatography and tandem mass spectrometry. Concerns regarding ion pair partitioning that could result in erroneous results due to interactions between compounds within a mixture are discussed.
authors.affiliation: Department of Chemistry, AstraZeneca R&D Charnwood, Loughborough, Leicestershire, UK. mark.wenlock@astrazeneca.com
authors.forename: Mark C
authors.initials: MC
authors.lastname: Wenlock
authors.forename: Tim
authors.initials: T
authors.lastname: Potter
authors.forename: Patrick
authors.initials: P
authors.lastname: Barton
authors.forename: Rupert P
authors.initials: RP
authors.lastname: Austin
mesh_terms: D001681:Biological Assay / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D015203:Reproducibility of Results; D012995:Solubility
chemical_list: D008055:Lipids