Partition coefficient by high-pressure liquid chromatography

Mirrlees, M. S., Moulton, S. J., Murphy, C. T., Taylor, P. J., Direct measurement of octanol-water partition coefficients by high-pressure liquid chromatography, J. Med. Chem. 1976, 39, 615-619. 

Mirrlees MS, Moulton SJ, Murphy CT et al. (1976) Direct measurement of octanol-water partition coefficients by high-pressure liquid chromatography. J Med Chem 19 615-619 Pagliara A, Khamis E, Thrinh A et al. (1995) Structural properties governing retention mechanisms on RP-HPLC stationary phases used for lipophilicity measurements. J Liquid Chromatography 18 1721-1745 Slater B, McCormack A, Avdeef A et al. (1994) pH-Metric log P. 4. Comparison of Partition Coefficients Determined by Shake-Flask, HPLC and Potentiometric Methods. J Phar-maceut Sci 83 1280-1283... 

McCall, J., Liquid-Liquid Partition Coefficients by High Pressure Liquid Chromatography, V Med. Chem., 18, 549-52 (1975). 

Mirrlees, M., S. Moulton, C. Murphy and P. Taylor, Direct Measurement of Octanol-Water Partition Coefficients by High Pressure Liquid Chromatography," J. Med. Chem.,13, 615-19(1976). 

Yamana. T., Novel Method for Determination of Partition Coefficients of Penicillins and Cephalosporins by High Pressure Liquid Chromatography," J. Pharm. Sci., 66. 747-49 (1977). 

Unger, S. H. Cook, J. R. Hollenberg, J. S., Simple procedure for determining octanol-aqueous partition, distribution, and ionization coefficients by reverse-phase high-pressure liquid chromatography, J. Pharm. Sci. 67, 1364—1366 (1978). 

Mishra, D.S., Yalkowsky, S.H. (1991) Estimation of vapor pressure of some organic compounds. Ind. Eng. Chem. Res. 30,1609-1612. Miyake, K., Tereda, H. (1982) Determination of partition coefficients of very hydrophobic compounds by high-performance liquid chromatography on glyceryl-coated controlled-pore glass. J. Chromatogr. 240, 9-20. 

Miyake, K., Kitaura, R, Mizuno, N., Tereda, H. (1987) Determination of partition coefficient and acid dissociation constant by high-performance liquid chromatography on porous polymer gel as a stationary phase. Chem. Pharm. Bull. 35(1), 377-388. Moriyoshi, T., Kaneshina, S., Aihara, K., Yahumoto, K.(1975) Mutual soluhihty of 2-hutanol + water under high pressures. J Chem. Thermodyn. 6, 537-545. 

Unger, S.H., Cook, J.R. and Hollenberg, J.S. (1978). Simple Procedure for Determining Octanol-Aqueous Partition, Distribution, and Ionization Coefficients by Reversed-Phase High-Pressure Liquid Chromatography. J.Pharm.Sci., 67,1364-1367. 

Other molecular properties have been also proposed to model the hydrophobic interactions. The parachor, which is related to the surface tension of a compound (139, 140) represents mainly the intermolecular interactions in a liquid. The Hildebrand-Scott solubility parameter, 6, (141) is related to intermolecular van der Waals forces and the closely related molar attraction constant, F, is obtained by multiplying 6 by the molar volume (142). The partition coefficient between two solvents can be obtained from the solubility parameters and the molar volumes of the solute and the solvents (193). This relationship is based on regular solution theory (194) and the assumption that the partial molar volumes of the solute is not different from its molar volume. Recently this has been criticized and a new derivation was proposed (195) in which the partial molar volumes are taken into account. The molar refractivity, MR, is related to dispersion forces and can be obtained as a sum of the partial molar refractivi-ties assigned to atoms and bonds (140, 143). These parameters have been compared (144) to establish their relative applicability to correlations with biological activity. The conclusion was that logP and molecular refractivity were the best parameters. Parameters obtained from high pressure liquid chromatography (144,... 

The octanol-water-partition coefficient (Kow) is the most frequently cited measure of environmental partitioning behavior. Partition coefficients traditionally have been determined by some variation on the shake-flask method, however, over the past several years high-pressure liquid chromatography has been shown to measure octanol-water partition coefficients accurately over a wide range of values with greater ease. 

Column and high performance liquid chromatography (HPLC) methods for measurement of solubility, octanol-water partition coefficient, and vapor pressure which are replacing the older equilibrium methods tend to underestimate aqueous solubility and vapor pressure and tend to overestimate the octanol-water partition coefficient. The standard deviation for both the equilibrium and dynamic systems are similar, but calibration between systems is necessary to insure that they agree. The range of errors for both types of measurement as mentioned in the literature are well within the range predicted by the computer-simulated error distributions generated in this report. The measurement error... 

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