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

Area of Science:

• Chromatography
• Biophysical Chemistry
• Environmental Science

Background:

• Estimating biological activity often relies on 1-octanol/water partition coefficients or chromatographic retention parameters.
• Bulk phases may not accurately model partitioning in biological membranes.
• Existing chromatographic stationary phases lack the necessary chain density to mimic biomembranes effectively.

Purpose of the Study:

• To develop and evaluate a novel derivatization scheme for silica surfaces to create high-density stationary phases.
• To assess the suitability of these densely bonded reversed-phase stationary phases as models for biomembrane partitioning.
• To compare the predictive power of these new phases with traditional methods for estimating bioavailability.

Main Methods:

• Development of a new method for derivatizing silica surfaces to achieve high alkyl chain density.
• Utilizing a C-18 column with high alkyl chain density for chromatographic analysis.
• Measuring chromatographic retention for pesticides, polycyclic aromatic hydrocarbons (PAHs), and barbiturates.

Main Results:

• Densely bonded reversed-phase stationary phases were shown to mimic biomembrane partitioning more effectively than bulk-phase octanol.
• Correlations between the logarithm of the retention factor (log k'w) and bioavailability were equivalent or superior to those using the octanol/water partition coefficient.
• This improved correlation was observed across diverse chemical classes including pesticides, PAHs, and barbiturates.

Conclusions:

• High alkyl chain density stationary phases provide a superior model for biomembrane partitioning compared to traditional methods.
• Chromatographic retention on these phases offers a more accurate prediction of bioavailability.
• This advancement has significant implications for environmental risk assessment and drug discovery.