Determination of the hydrophobicity of local anesthetic agents

Hydrophobicity, a term used to describe a fundamental physicochemical prope rty of local anesthetics, was in the past obtained by octanol/buffer partit ioning. It has been suggested that the octanol method, despite its obvious advantages, also has some drawbacks. HPLC has become an attractive alternat ive for the measurement of hydrophobicity and has been applied to local ane sthetics recently, However, the methods in current use for measuring the hy drophobicity of local anesthetics suffer from a number of limitations and r emain obscure, This study introduces a new HPLC method for measuring the hy drophobicity of eight local anesthetics in current clinical use. Using a C- 18 derivatized polystyrene-divinylbenzene stationary phase HPLC column, the log k(w)' values of local anesthetics were determined by measuring the cap acity factor k(i)' in the process of chromatographic separation using a hyd rophobic stationary phase and a hydrophilic mobile phase. A rapid reversed- phase HPLC method was developed to directly measure log k(w)' of eight loca l anesthetics. A high correlation between log k(w)' and hydrophobicity (log P-oet) from the traditional shake-flask method was obtained for the local anesthetics, demonstrating the reliability of the method. The results revea l an improved method for measuring the hydrophobicity of the local anesthet ic agents in the unionized form, This simple, sensitive and reproducible ap proach may serve as a valuable tool for describing the physicochemical prop erties of novel local anesthetics. (C) 2001 Academic Press.