Abstract
The retention behavior of monosubstituted pyrazines was investigated by comparing the hydrophobic contribution of each substituent (κ) to the capacity factor obtaiend from reversed-phase high-performance liquid chromatography (HPLC), using a C18 capsule-type column and methanol-water eluents of various compositions. The mobile phase dependency of κ showed that the retention mechanism varied with the substituent, especially in mobile phases with very high water content, due to the intervention of the selective solute-solvent interactions. Under such circumstances, the capacity factor (log k') obtaiend from HPLC methods correlated very poorly with the octanol-water partition coefficient (log P). The log k' for pyrazines with only alkyl and/or alkoxy groups was measured and the correlation with log P was examined. An excellent linear correlation was obtained with the eluent containing about 30% methanol. However, at other methanol concentrations, the log k' values of the alkyl and alkoxy derivatives correlated with log P by two separated linear equations. The use of log kW (log k' at 100% water), which has so far been considered to be the best index of hydrophobicity, failed to simulate log P.
