|Reference : Implementation of a Design Space Approach for Enantiomeric Separations in Polar Organ...|
|Scientific journals : Article|
|Human health sciences : Pharmacy, pharmacology & toxicology|
|Implementation of a Design Space Approach for Enantiomeric Separations in Polar Organic Solvent Chromatography|
|Nistor, Iolanda |
|Lebrun, Pierre [Université de Liège - ULg > Département de pharmacie > Chimie analytique >]|
|Ceccato, Attilio [Université de Liège - ULg > Département de pharmacie > Analyse des médicaments >]|
|Lecomte, Frédéric [Université de Liège - ULg > Département de pharmacie > Chimie analytique >]|
|Slama, I |
|Oprean, R |
|Badarau, E |
|Dufour, F |
|Dossou, K.S.S. |
|Fillet, M |
|Liégeois, Jean-François [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]|
|Hubert, Philippe [Université de Liège - ULg > Département de pharmacie > Chimie analytique >]|
|Rozet, Eric [Université de Liège - ULg > Département de pharmacie > Chimie analytique >]|
|Journal of Pharmaceutical & Biomedical Analysis|
|Yes (verified by ORBi)|
|[en] Design Space ; design of experiment ; Enantioseparation ; HPLC-UV ; polar organic solvent chromatography ; SK channels modulators|
|[en] This paper focuses on implementing a Design Space approach and on the critical process parameters (CPPs) to consider when applying the Quality by Design (QbD) concepts outlined in ICH Q8(R2), Q9 and Q10 to analytical method development and optimization for three chiral compounds developed as modulators of small conductance calcium-activated potassium (SK) channels. In this sense, an HPLC method using a polysaccharide-based stationary phase containing a cellulose tris (4-chloro-3-methylphenylcarbamate) chiral selector in polar organic solvent chromatography mode was considered. The effects of trifluoroacetic acid (TFA) and n-hexane concentration in an acetonitrile (MeCN) mobile phase were investigated under a wide range of column temperatures.
Good correlations were found between the observed data obtained after using a central composite design and the expected chromatographic behaviours predicted by applying the design of experiments-design space (DoE-DS) methodology. The critical quality attribute represented here by the separation criterion (Scrit) allowed assessing the quality of the enantioseparation. Baseline separation for the compounds of interest in an analysis time of less than 20 minutes was possible due to the original and powerful tools applied which facilitated an enhanced method comprehension.
Finally, the advantage of the DoE-DS approach resides in granting the possibility to concurrently assess robustness and identify the optimal conditions which are compound dependent.
|Researchers ; Professionals ; Students|
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