Comparative Lipophilicity of Morphine Derivatives

Lipophilicity is an important physicochemical characteristic of compounds having potential use in the treatment of humans and animals. Morphine and its semisynthetic derivatives have effects on mu (mu), kappa (kappa), and delta (delta) opioid receptors, and their physiological, pharmacological, and therapeutic effects mainly depend on their distribution in the body. The progress in separation techniques has made it possible to use modern methods to determine lipophilic/hydrophilic character of small amounts of organic compounds in just a few minutes. In addition to the classical determination of lipophilicity (shaken-flask method), other experimental methods (such as reversed-phase thin-layer chromatography, distribution-pH profile, etc.) and calculations based on the molecular composition are widely used. The lipophilic character of several morphine derivatives was determined using reversed-phase thin-layer chromatography and also high-performance liquid chromatography (HPLC) method. The results are graphically compared. Lipophilicity (log P) calculation using Pallas 3.8 program was successful only for certain morphine derivatives. Parameters derived from the experimental results of reversed-phase thin-layer chromatography and those of a special HPLC column were well comparable.