Lemasson Elise, Bertin Sophie, Hennig Philippe, Lesellier Eric, West Caroline
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.
Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France.
J Chromatogr A. 2016 Nov 11;1472:117-128. doi: 10.1016/j.chroma.2016.10.045. Epub 2016 Oct 18.
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.
对作为潜在候选药物合成的有机产物进行杂质分析是一项重大的分析挑战。需要采用互补的分析方法以确保检测到所有杂质。高效液相色谱法（HPLC）和超临界流体色谱法（SFC）均可用于此目的。在本研究中，我们使用包含140种药物化合物的大型数据集对超高效液相色谱法（UHPLC）和超高效超临界流体色谱法（UHPSFC）进行了比较。选择了四种先前优化的方法（每种技术两种）以确保实现快速的高分辨率分离。基于响应率、峰容量、峰形和杂质检测能力（紫外检测）对这四种方法进行了评估。还评估了所有方法之间的正交性。对于本研究中包含的140种化合物，最佳的UHPLC方法和UHPSFC方法提供了相当的质量。此外，发现它们具有高度的正交性。最后，通过实际示例说明了UHPLC和UHPSFC联合用于杂质分析的潜力。
