title: High-throughput determination of octanol/water partition coefficients using a shake-flask method and novel two-phase solvent system.
abstract: A high-throughput method for determining the octanol/water partition coefficient (P(o/w)) of a large variety of compounds exhibiting a wide range in hydrophobicity was established. The method combines a simple shake-flask method with a novel two-phase solvent system comprising an acetonitrile-phosphate buffer (0.1 M, pH 7.4)-1-octanol (25:25:4, v/v/v; AN system). The AN system partition coefficients (K(AN)) of 51 standard compounds for which log P(o/w) (at pH 7.4; log D) values had been reported were determined by single two-phase partitioning in test tubes, followed by measurement of the solute concentration in both phases using an automatic flow injection-ultraviolet detection system. The log K(AN) values were closely related to reported log D values, and the relationship could be expressed by the following linear regression equation: log D=2.8630 log K(AN) -0.1497(n=51). The relationship reveals that log D values (+8 to -8) for a large variety of highly hydrophobic and/or hydrophilic compounds can be estimated indirectly from the narrow range of log K(AN) values (+3 to -3) determined using the present method. Furthermore, log K(AN) values for highly polar compounds for which no log D values have been reported, such as amino acids, peptides, proteins, nucleosides, and nucleotides, can be estimated using the present method. The wide-ranging log D values (+5.9 to -7.5) of these molecules were estimated for the first time from their log K(AN) values and the above regression equation.
authors.affiliation: Division of Pharmaceutical and Biomedical Analysis, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Morikawa
authors.affiliation: Division of Pharmaceutical and Biomedical Analysis, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Suzuka
authors.affiliation: Division of Pharmaceutical and Biomedical Analysis, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shoji
authors.affiliation: Division of Pharmaceutical and Biomedical Analysis, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shibusawa
authors.affiliation: Division of Pharmaceutical and Biomedical Analysis, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: yanagida@toyaku.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Yanagida
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods*; D000442:Octanols / Q000032:analysis* / Q000737:chemistry; D012997:Solvents / Q000032:analysis* / Q000737:chemistry; D014867:Water / Q000032:analysis* / Q000737:chemistry
chemical_list: D000442:Octanols; D012997:Solvents; D014867:Water
keywords: Amino acids; Nucleotides; Octanol/water partition coefficient; Peptides; Shake-flask method; Two-phase solvent system