Enantiomeric impurity determination in capillary electrophoresis using a highly-sulfated cyclodextrins-based method

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis

Background:

• Ensuring chiral purity is critical for pharmaceutical efficacy and safety.
• Existing methods for chiral separation may not be sensitive enough for trace impurity detection.

Purpose of the Study:

• To develop and validate capillary electrophoresis (CE) methods for determining chiral purity of pharmaceutical compounds.
• To achieve sensitive detection of trace enantiomeric impurities (0.1%) in drug substances.

Main Methods:

• Utilized capillary electrophoresis (CE) with highly-sulfated cyclodextrins as chiral selectors.
• Applied a chiral separation strategy to four basic drugs: propranolol, atenolol, chlorpheniramine, and tryptophan methylester.
• Determined method linearity, quantification limits for trace enantiomers, and measurement precision.

Main Results:

• Validated CE methods capable of determining 0.1% impurity levels of the distomer in the presence of 99.9% eutomer.
• Simulations revealed that a baseline resolution of 1.5 is insufficient for accurate impurity determination.
• Two alternative methods were proposed to improve impurity separation and quantification.

Conclusions:

• Highly-sulfated cyclodextrins in CE provide a robust platform for sensitive chiral purity assessment.
• Standard resolution criteria may need adjustment for accurate trace impurity analysis in pharmaceuticals.
• The developed methods offer a reliable approach for quality control of enantiomerically pure drugs.