Lipophilicity of opioids determined by a novel micromethod.

The lipophilicity of various mu-selective opioids was determined by measuring their distribution between n-octanol and Tris.HCl buffer, pH 7.4, by a procedure requiring submicromolar concentrations (submilligram amounts) of the compounds. After partitioning at 25 degrees C, the concentrations of opioids in the aqueous phase was quantified by their displacement of bound [3H]Tyr-Ala-Gly-(Me)Phe-Gly-ol (DAMGO) from opioid receptor in brain membranes. The obtained distribution coefficients (log Papp) agreed well with respective values determined previously with other, less sensitive or more cumbersome, methods of quantitation. The procedure is precise and versatile, and offers the routine assessment of lipophilicity as part of the in vitro characterization of opioids frequently available in limited quantities. In principle, the method is applicable to any compound whose binding to its receptor is quantifiable.