Chiral separations by nonaqueous capillary electrophoresis

Area of Science:

• Analytical Chemistry
• Separation Science
• Pharmaceutical Analysis

Background:

• Chiral separation of pharmaceutical compounds is crucial for drug safety and efficacy.
• Nonaqueous capillary electrophoresis (NACE) offers an alternative to aqueous methods for separating chiral molecules.
• Cyclodextrins (CDs) are widely used chiral selectors in separation techniques.

Purpose of the Study:

• To investigate the chiral separation of pharmaceutical racemic amines using NACE.
• To evaluate the influence of different organic solvents (formamide, N-methylformamide, N,N-dimethylformamide) on chiral separations compared to aqueous systems.
• To determine the binding constants of model drugs with beta-cyclodextrin in various solvent systems.

Main Methods:

• Nonaqueous capillary electrophoresis (NACE) was employed for chiral separations.
• Beta- and gamma-cyclodextrins (CDs) and their derivatives were used as chiral selectors.
• Binding constants were determined for trimipramine, mianserin, and thioridazine with beta-CD in water, 6 M urea, formamide, N-methylformamide, and N,N-dimethylformamide.

Main Results:

• Binding constants of trimipramine, mianserin, and thioridazine with beta-CD decreased significantly from water to organic solvents (approx. 10^4 in water to 10^-2 in DMF).
• Optimal cyclodextrin concentrations varied greatly, from micromolar in aqueous media to millimolar in formamide.
• Acceptable resolutions were achieved even at non-optimum concentrations by adjusting parameters like ionic strength, tetraalkylammonium addition, and temperature, albeit with longer analysis times.

Conclusions:

• Solvent choice profoundly impacts cyclodextrin binding and chiral separation efficiency in NACE.
• NACE with CDs in organic solvents provides a viable alternative for chiral amine separations.
• Understanding solvent effects and binding constants is key for developing robust chiral separation methods.