title: Chemometric quality control of chromatographic purity.
abstract: It is common practice in chromatographic purity analysis of pharmaceutical manufacturing processes to assess the quality of peak integration combined by visual investigation of the chromatogram. This traditional method of visual chromatographic comparison is simple, but is very subjective, laborious and seldom very quantitative. For high-purity drugs it would be particularly difficult to detect the occurrence of an unknown impurity co-eluting with the target compound, which is present in excess compared to any impurity. We hypothesize that this can be achieved through Multivariate Statistical Process Control (MSPC) based on principal component analysis (PCA) modeling. In order to obtain the lowest detection limit, different chromatographic data preprocessing methods such as time alignment, baseline correction and scaling are applied. Historical high performance liquid chromatography (HPLC) chromatograms from a biopharmaceutical in-process analysis are used to build a normal operation condition (NOC) PCA model. Chromatograms added simulated 0.1% impurities with varied resolutions are exposed to the NOC model and monitored with MSPC charts. This study demonstrates that MSPC based on PCA applied on chromatographic purity analysis is a powerful tool for monitoring subtle changes in the chromatographic pattern, providing clear diagnostics of subtly deviating chromatograms. The procedure described in this study can be implemented and operated as the HPLC analysis runs according to the process analytical technology (PAT) concept aiming for real-time release.
authors.affiliation: Quality & Technology, Department of Food Science, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark; Novo Nordisk A/S, 2880 Bagsvaerd, Denmark. krfl@novonordisk.com
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Laursen
authors.forename: Søren Søndergaard
authors.initials: SS
authors.lastname: Frederiksen
authors.forename: Casper
authors.initials: C
authors.lastname: Leuenhagen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Bro
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003198:Computer Simulation; D004340:Drug Contamination / Q000517:prevention & control; D008962:Models, Theoretical; D015999:Multivariate Analysis; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000592:standards; D025341:Principal Component Analysis; D012815:Signal Processing, Computer-Assisted
chemical_list: D004364:Pharmaceutical Preparations