title: Accurate automated logPo/w measurement by gradient-flow liquid-liquid partition chromatography. Part 1. Neutral compounds.
abstract: There is a continuing need for a method which can measure logPoctanol/water accurately and precisely. Liquid-liquid partition chromatography is ideally suited for this as the retention time is a direct function of the partition or distribution coefficient. However, the range of measurements using isocratic-flow conditions is limited by the log-linear relation between run time and logPo/w. The use of gradient-flow programming and short columns gives a more versatile procedure, so that appropriate data points can be collected at both the low and high ends of the chromatographic run, corresponding to logPo/w values between 1 and 4. At the same time the precision, accuracy and versatility of the method are kept. This study is a validation of the procedure and measures the logPo/w on 23 representative pharmaceuticals, comprising a mixed set of neutral compounds. The linear plot fitting micropartition logPo/w and those found in literature shows a slope close to unity and a residuum close to zero. This indicates that gradient-flow micropartition chromatography is ruled by partitioning between octanol and the aqueous phase.
authors.affiliation: Oroxcell SAS, 102 Route de Noisy, 93230 Romainville, France. sandrine.demare@oroxcell.com
authors.forename: Sandrine
authors.initials: S
authors.lastname: Demare
authors.forename: Bryan
authors.initials: B
authors.lastname: Slater
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Lacombe
authors.forename: Delphine
authors.initials: D
authors.lastname: Breuzin
authors.forename: Christophe
authors.initials: C
authors.lastname: Dini
mesh_terms: D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D006854:Hydrocortisone / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D000442:Octanols / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D015203:Reproducibility of Results; D013739:Testosterone / Q000032:analysis; D014867:Water / Q000737:chemistry*
chemical_list: D000442:Octanols; D004364:Pharmaceutical Preparations; D014867:Water; D013739:Testosterone; D006854:Hydrocortisone