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Publication

Drug impurity profiling in supercritical fluid chromatography

Book - Dissertation

Subtitle:Understanding the influence of the parameters required for method development
Drug impurity profiling is regulated by stringent drug registration procedures established by regulatory authorities. Currently high performance liquid chromatography (HPLC) is the mainstay technique used in the pharmaceutical industry for this purpose. However, the quest for complementary, faster, cheaper, greener and more efficient techniques will always be strong. Supercritical fluid chromatography (SFC) fulfils these needs and because of the recent instrumental improvements, it is now being explored for drug impurity profiling. The aim of this thesis was to investigate different experimental parameters, mainly the stationary phase, modifier composition, column temperature and back-pressure, and their effect on separation in SFC, within the context of method development for drug impurity profiling. Initially a database of stationary phases was characterized using retention profiles of a representative set of pharmaceutical compounds. Several chemometric techniques and an adapted linear solvation energy relationship (LSER) model were used to cluster the columns in sub-groups of similar properties and subsequently select a small set of dissimilar phase to be used for further method development. In the second phase, the influence of binary organic solvent blends as modifier on the retention and separation of achiral components was investigated. This was followed by a method optimization study to fine-tune the column temperature and back-pressure using a response surface approach. Finally the complete methodology was tested on a pharmaceutical drug and its impurities from the industry. The main knowledge obtained from the different phases of the thesis was brought together in a generic strategy.
Publication year:2017
Keywords:drug impurity