Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development
Апстракт
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 en...d 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.
Кључне речи:
bupropion / chaotropic chromatography / experimental design / impurities / quality-by-designИзвор:
Pharmaceuticals, 2022, 15, 10Издавач:
- MDPI
Институција/група
PharmacyTY - JOUR AU - Gkountanas, Kostas AU - Malenović, Anđelija AU - Dotsikas, Yannis PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4312 AB - 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. PB - MDPI T2 - Pharmaceuticals T1 - Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development VL - 15 IS - 10 DO - 10.3390/ph15101196 ER -
@article{ author = "Gkountanas, Kostas and Malenović, Anđelija and Dotsikas, Yannis", year = "2022", 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.", publisher = "MDPI", journal = "Pharmaceuticals", title = "Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development", volume = "15", number = "10", doi = "10.3390/ph15101196" }
Gkountanas, K., Malenović, A.,& Dotsikas, Y.. (2022). Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development. in Pharmaceuticals MDPI., 15(10). https://doi.org/10.3390/ph15101196
Gkountanas K, Malenović A, Dotsikas Y. Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development. in Pharmaceuticals. 2022;15(10). doi:10.3390/ph15101196 .
Gkountanas, Kostas, Malenović, Anđelija, Dotsikas, Yannis, "Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development" in Pharmaceuticals, 15, no. 10 (2022), https://doi.org/10.3390/ph15101196 . .