Use of the three-phase model and headspace analysis for the facile determination of all partition/association constants for highly volatile solute-cyclodextrin-water systems.

A versatile method for measuring the partition coefficients of volatile analytes with an aqueous pseudophase using headspace gas chromatography is reported. A "three-phase" model accounts for all equilibria present in the system, including the partitioning of the analyte in the gas and aqueous phases to the pseudophase. This method is applicable to a wide variety of volatile analytes and aqueous pseudophases, providing that sufficient pseudophase may be used to reduce the analyte partial pressure. Generally, the method offers good reproducibility and high sensitivity. The associations of five volatile analytes (hydrogen sulfide, methanethiol, dimethyl sulfide, dichloromethane, and ethyl ether) with various cyclodextrins were examined. All analytes were found to partition preferentially to the cyclodextrin pseudophase compared to the aqueous phase. In addition, several analyte-cyclodextrin combinations formed insoluble complexes in solution that enhanced the extraction of the analyte from the gas and aqueous phases. Derivatization of the cyclodextrins generally decreased the extent of analyte-cyclodextrin interaction.