Bioavailability estimation by reversed-phase liquid chromatography: high bonding density C-18 phases for modeling biopartitioning processes.

There have been many attempts to estimate biological activity with either 1-octanol/water partition coefficients or chromatographic retention parameters. Bulk phases may not be appropriate, however, for modeling a partitioning process in an interphase such as biological membranes. Chromatographic stationary phases can be argued as having structure similar to a membrane because of chain organization; however, the density of the grafted stationary-phase chains in commercially available stationary phases is much too low to provide a suitable model. We have previously developed a new scheme for derivatizing silica surfaces that produces stationary phases of significantly higher chain density than traditional methods. Investigation of the molecular mechanism and thermodynamics of solute partitioning into the different phases has shown that densely bonded reversed-phase stationary phases mimic partitioning to a biomembrane better than does bulk-phase octanol. Here we report chromatographic retention for pesticides, PAHs, and barbiturates using a C-18 column with high alkyl chain density, and in all cases, correlations of log k'w with bioavailability are equivalent to or better than correlations of bioavailability with the octanol/water partition coefficient.