Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis

Background:

• Accurate quantification of bupropion and its impurities is crucial for pharmaceutical quality control.
• Existing methods may require optimization for comprehensive impurity profiling.

Purpose of the Study:

• To develop and validate a novel chaotropic chromatography method for bupropion and impurity determination.
• To apply analytical quality-by-design (AQbD) principles for robust method development.

Main Methods:

• Development of a chaotropic chromatography method incorporating gradient elution.
• Utilized screening fractional factorial design and Box-Behnken design for parameter optimization.
• Employed Monte Carlo simulations to define the design space (DS).

Main Results:

• A robust method was established with optimized parameters: 37.5-70% acetonitrile gradient, 45 mM potassium hexafluorophosphate, and gradient start at 10 min.
• The method demonstrated efficient separation and reliable quantification of bupropion and five impurities.
• The validated method was successfully applied to Wellbutrin® tablets.

Conclusions:

• The developed chaotropic chromatography method, guided by AQbD, provides a reliable and efficient means for bupropion and impurity analysis.
• This approach ensures high probability of method success within the defined design space.
• The validated method meets regulatory requirements (ICH guidelines) for pharmaceutical analysis.