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 eit her 1-octanol/water partition coefficients or chromatographic retentio n parameters. Bulk phases may not be appropriate, however, for modelin g 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 dens ity of the grafted stationary-phase chains in commercially available s tationary phases is much too low to provide a suitable model. We have previously developed a new scheme for derivatizing silica surfaces tha t produces stationary phases of significantly higher chain density tha n traditional methods, investigation of the molecular mechanism and th ermodynamics of solute partitioning into the different phases has show n that densely bonded reversed-phase stationary phases mimic partition ing to a biomembrane better than does bulk-phase octanol. Here we repo rt chromatographic retention for pesticides, PAHs, and barbiturates us ing a C-18 column with high alkyl chain density, and in all cases, cor relations of log k'(w) with bioavailability are equivalent to or bette r than correlations of bioavailability with the octanol/water partitio n coefficient.