Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development

Abstract

A novel chaotropic chromatography method for the quantitative determination of bupropion and its impurities, following analytical quality-by-design (AQbD) principles, is presented. The analytical target profile (ATP) was defined on the basis of the efficient separation and reliable determination of bupropion and its five impurities in tablets. Preliminary experiments revealed the need for the addition of a gradient elution part. A screening fractional factorial experimental design was employed to select the critical method parameters (CMPs) and a Box–Behnken design (BBD) was utilized to investigate their influence on predefined critical method attributes (CMAs). In order to compute the design space (DS), where CMPs meet predefined acceptance limits with a high level of probability (π ≥ 85%), Monte Carlo simulations were performed. The working point selected from the DS corresponded to the following conditions: 37.5% acetonitrile at the start of the gradient program (up to 70% at the end of the gradient program), 45 mM of potassium hexafluorophosphate in the water phase, and the start of the linear gradient step in the gradient program at 10 min. The method was validated according to ICH guidelines and applied to the analysis of Wellbutrin® tablets containing bupropion hydrochloride.

Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination

“…ZPS and its five impurities are substances with basic character. Based on our previous experience with such solutes [ 18 , 20 , 21 ], we decided to add column friendly chaotropic reagents to the mobile phase to achieve appropriate peak shape and retention. Anions, which are commonly part of the mobile phase in chaotropic chromatography, are hexafluorophosphate, perchlorate, or trifluoroacetate.…”