Determination of Residual Solvents in Pharmaceuticals by Static Headspace Gas Chromatography Using Natural Deep Eutectic Solvents as Mediums: A Partition Coefficients Study

A relatively new application of natural deep eutectic solvents (NADESs) as eco-friendly dilution mediums in static headspace gas chromatography (SHS-GC) was further studied. The partition coefficients of twelve organic solvents in NADESs were determined by SHS-GC. Eight NADESs were prepared with choline chloride and carboxylic acids, polyols and urea in different molar ratios. The twelve organic solvents included four haloalkanes, four aprotic solvents, two alcohols, and two alkanes. The partition coefficients ( K ) of each solvent in different NADESs were determined and discussed. The log K values of alkanes and aprotic solvents in NADESs were low, while the log K of haloalkanes and alcohols was high. That is, alkanes and aprotic solvents in NADESs had better headspace efficiency, indicating that the interaction between the solvents and the NADESs played an important role. The relationship between the log K and the properties of NADESs and organic solvents was further discussed. As an example, the method was applied to determine the residual solvents in paroxetine by SHS-GC with appropriate NADES. This study is beneficial for the selection of suitable NADESs as green mediums for the detection of residual solvents in pharmaceuticals.