Application of new methodologies based on design of experiments, independent component analysis and design space for robust optimization in liquid chromatography

作者：Debrus Benjamin^*; Lebrun Pierre; Ceccato Attilio; Caliaro Gabriel; Rozet Eric; Nistor Iolanda; Oprean Radu; Ruperez Francisco J; Barbas Coral; Boulanger Bruno; Hubert Philippe

来源：Analytica Chimica Acta, 2011, 691(1-2): 33-42.

DOI：10.1016/j.aca.2011.02.035

• High-performance liquid chromatography
• Method development
• Separation optimization
• Experimental design
• Design space
• Independent component analysis

HPLC separations of an unknown sample mixture and a pharmaceutical formulation have been optimized using a recently developed chemometric methodology proposed by W. Dewe et al. in 2004 and improved by P. Lebrun et al. in 2008. This methodology is based on experimental designs which are used to model retention times of compounds of interest. Then, the prediction accuracy and the optimal separation robustness, including the uncertainty study, were evaluated. Finally, the design space (ICH Q8(R1) guideline) was computed as the probability for a criterion to lie in a selected range of acceptance. Furthermore, the chromatograms were automatically read. Peak detection and peak matching were carried out with a previously developed methodology using independent component analysis published by B. Debrus et al. in 2009. The present successful applications strengthen the high potential of these methodologies for the automated development of chromatographic methods.

• 出版日期2011-4-8