title: Comparison of ultra-high performance methods in liquid and supercritical fluid chromatography coupled to electrospray ionization - mass spectrometry for impurity profiling of drug candidates.
abstract: Impurity profiling of organic products synthesized as possible drug candidates represents a major analytical challenge. Complementary analytical methods are required to ensure that all impurities are detected. Both high-performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) can be used for this purpose. In this study, we compared ultra-high performance HPLC (UHPLC) and ultra-high performance SFC (UHPSFC) using a large dataset of 140 pharmaceutical compounds. Four previously optimized methods (two on each technique) were selected to ensure fast high-resolution separations. The four methods were evaluated based on response rate, peak capacity, peak shape and capability to detect impurities (UV). The orthogonality between all methods was also assessed. The best UHPLC method and UHPSFC methods provided comparable quality for the 140 compounds included in this study. Moreover, they were found to be highly orthogonal. At last, the potential of the combined use of UHPLC and UHPSFC for impurity profiling is illustrated with practical examples.
authors: Univ Orléans, Institut de Chimie Organique et Analytique (ICOA), CNRS UMR 7311, Pôle de Chimie, rue de Chartres, B.P. 6759, 45067 Orléans, Cedex 2, France.
authors: Elise
authors: E
authors: Lemasson
authors: Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France.
authors: Sophie
authors: S
authors: Bertin
authors: Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France.
authors: Philippe
authors: P
authors: Hennig
authors: Univ Orléans, Institut de Chimie Organique et Analytique (ICOA), CNRS UMR 7311, Pôle de Chimie, rue de Chartres, B.P. 6759, 45067 Orléans, Cedex 2, France.
authors: Eric
authors: E
authors: Lesellier
authors: Univ Orléans, Institut de Chimie Organique et Analytique (ICOA), CNRS UMR 7311, Pôle de Chimie, rue de Chartres, B.P. 6759, 45067 Orléans, Cedex 2, France. Electronic address: caroline.west@univ-orleans.fr.
authors: Caroline
authors: C
authors: West
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D066264:Datasets as Topic; D004340:Drug Contamination; D004364:Pharmaceutical Preparations / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004364:Pharmaceutical Preparations
keywords: High-resolution separations; Impurity profiling; Orthogonal methods; Performance comparison; Pharmaceutical ingredients