STUDY OF THE LIPOPHILICITY OF ARYLPROPIONIC NON-STEROIDAL ANTI-INFLAMMATORY DRUGS. A COMPARISON BETWEEN LC RETENTION DATA ON A POLYMER-BASED COLUMN AND OCTANOL-WATER PARTITION COEFFICIENTS

Abstract

Molecular lipophilicity can be expressed by log Pow or, more conveniently, by log kw, i.e., determined by the traditional shake-flask technique, or by reversed-phase high performance liquid chromatography (RP-HPLC). Moreover, the unionized form of solutes is usually taken as the reference state for the measurement of lipophilicity. This can be problematic for the RP-HPLC determination of lipophilicity of acidic compounds due to the limited pH operating range of silica bonded phases. The measured dissociation constant values (pKa) of the twelve arylpropionic non steroidal antiinflammatory drugs (NSAIDs) are comprised between 3.80 and 5.70; consequently, the lipophilicities of the unionized forms must be measured at pH below 2. Accordingly, their capacity factors (log kw) were determined on a column packed with a hydrophilic polymethacrylate gel having octadecyl groups. This RP-column allows separations at low pH values of the mobile phase. In practice, the values of log kw are obtained by a series of isocratic measurements at various compositions of binary acetonitrile-water eluents and extrapolation of the relationship between log k and volume fraction of organic solvent, φ, to 100% water. The 1-octanol-water partition coefficients (log Pow) of these NSAIDs were determined by the shake-flask technique using a conventional methodology. A significant linear relationship was obtained between log Pow and log kw with a slope close to unity, indicating similar intrinsic thermodynamic behaviour of these drugs for the two partitioning processes. This excellent correlation prompted us to validate this polymer-based column, to be useful for the determination of other acidic drug lipophilicity.