title: Simple procedure for determining octanol--aqueous partition, distribution, and ionization coefficients by reversed-phase high-pressure liquid chromatography.
abstract: The described simple, accurate, and precise reversed-phase high-pressure liquid chromatographic procedure is in excellent agreement with 1-octanol shake-flask partition or distribution coefficients over a 3.5 log range. A chemically bonded octadecylsilane support is persilated and coated with 1-octanol. With 1-octanol-saturated buffers as mobile phases, a stable baseline (compared to 1-octanol adsorbed on silica) is obtained rapidly, and the log relative retention times are highly correlated with unit slope to log distribution or partition coefficients obtained from the classical shake-flask procedures. Only relatively basic, unhindered pyridines deviate, probably because of binding with residual silinol sites. In addition, if the apparent pKa or pKab of an ionizable compound lies within the pH operating range of the column support, the apparent pKa or pKab usually can be determined simultaneously with log P by measuring the log distribution coefficient at several pH values. The procedure gives rapid results, requires little material, and can tolerate impurities.
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D007477:Ions; D008433:Mathematics; D000442:Octanols; D012995:Solubility; D014867:Water
chemical_list: D007477:Ions; D000442:Octanols; D014867:Water