[en] A new method to optimize liquid chromatography (LC) methods using a Quality by Design (QbD) approach is presented. This method is based on the use of design of experiments (DOE) and independent component analysis (ICA) to accurately estimate the modelled responses (that is, the retention times at the beginning, the apex, and the end) of each peak, even for coeluted peaks. The modelling of these responses usesmultiple linear regressions, while the propagation of the error affecting the responses and coming from the models is carried out by Monte Carlo simulation. The design space is determined as the region of assay factors where the probability to reach baseline-resolved peaks is higher than the desired level of quality. This
method was applied to the optimization of the separation of nine compounds in a mixture, yielding the design space and the demonstration of robustness of the method. Finally, the method was validated.
Research Center/Unit :
Centre Interfacultaire de Recherche du Médicament - CIRM - Département de Pharmacie
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Debrus, Benjamin ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique
Lebrun, Pierre ; Université de Liège - ULiège > HEC - École de gestion de l'ULiège > HEC-Ecole de gestion
Rozet, Eric ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique