Lipophilicity refers to the affinity of a drug for a lipid environment and is a key parameter related to its adequate drug-like properties and off-target effects. It is measured through the tendency of a compound to partition between a lipophilic organic phase and a polar aqueous phase to give logPo/w values. Depending on the compound characteristics different approaches may be applied for its calculation

Methodology

• Shake-flask: classical partition method generally applicable, also performed under OECD107 or OECD123 guidelines (under GLP). Under OECD107, the partition experiments in n-octanol/water are performed from the solid compound at three values of pH (logDpH).
• Chromatography: applicable to unionized compounds, is an approach combining the chromatographic retention of a compound with its hydrogen bond donor properties.
• Potentiometric titration: applicable to substances with acid-base properties, is performed in a T3 instrument. logPo/w values are obtained from the difference between the aqueous pKa of the species and the apparent pKa determined from dual phase titrations.

Turnaround time: 3 days for logPo/w and 3 weeks for logKow under OECD107 (GLP).