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Partition coefficient for physical chemistry testing
Most commonly, drugs are absorbed by passive diffusion across a lipophilic cell membrane into the blood. Therefore, lipophilicity is an important property of a drug that influences passive transport across cell membranes.
Partition coefficients are useful in estimating the distribution of drugs within the body, as it gives a measure of a solute’s hydrophobicity and a proxy for its membrane permeability.
The partition coefficient (P) is defined as the ratio of the equilibrium concentrations of a dissolved substance in a two-phase system consisting of two largely immiscible solvents. In drug development, lipophilicity is usually expressed by the partition between water and octan-1-ol using the shake flask method and measuring the distribution of the solute by UV/VIS spectroscopy.
Most drugs, however, are weak acids or weak bases that partially ionise when dissolved in water, therefore the distribution coefficient must be used. A faster method of log P can be determined using reverse phase high-performance liquid chromatography (HPLC).
