Lipophilicity influences absorption, and tissue distribution of a molecule. Hydrophobic molecules exhibit high propensity to non specifically binding to plasma proteins and to become metabolized by cytochromes P450.

The partition coefficient between octanol and water is the most widely used physicochemical determination of lipophilicity.

This test consists in measuring the octanol/water partition coefficient of a compound. The value determined informs about the lipophilicity of the molecule. The log D is a function of the pH. Its value must be indicated at a given pH.

Protocol

Matrix

PBS pH 7.4 and octanol
Volume ratios 970/20 ; 790/200 ; 330/660
ControlsRifampicin, Ketoconazole, Metoprolol
Analysis methodQuantitation in aqueous phase by HPLC-UV
Data deliveryLog D7.4
Replicate2

Note

A chromophore group on the molecule is required for detection.

Partition coefficients will be reported if comprised between -1.5 et 4. Upper limit depends on analysis sensitivity.

Chromatographic Hydrophobicity Index (CHI) method allows higher lipophilicities to be determined.

Advice

For optimal oral absorption, log D should be comprised between 0.5 and 2.

The difference log Doctanol