The pKa and log P values of morphine-6-â-D-glucuronide (M6G) and morphine-3-â-D-glucuronide (M3G) and a range of structurally-related opiates (morphine, normorphine, codeine, norcodeine, 6-acetylmorphine, diacetylmorphine, and buprenorphine) were accurately measured using a potentiometric approach. The measured lipophilicity profiles (pH 2-11, 0.15 M KCl matrix) of M3G and M6G were compared using a proton donor solvent (chloroform) and a proton acceptor solvent (propylene glycol dipelargonate, PGDP), in addition to octanol. The log P values and lipophilicity profiles of M6G and M3G determined in octanol-water have confirmed the unexpectedly high lipophilicity of the two glucuronides. These results show the importance of measuring the effect of pH on lipophilicity, since log D (pH 7.4) values gave a notably different order of lipophilicity for the opiates compared with log P. M6G, but not M3G, showed significant differences in log P between different types of partitioning solvents. The observed order of lipophilicities (log D, pH 7.4) was buprenorphine (3.93), diacetylmorphine (0.85), 6-acetylmorphine (0.61), codeine (0.22), morphine (-0.07), M6G (-0.79), M3G (-1.12), norcodeine (-1.26), and normorphine (-1.56).