ABSTRACT
Organic impurities in active pharmaceutical ingredients (APIs) are derived from many different sources during manufacturing and storage. They can be starting materials,1 intermediates,2 reagents, side-reaction products,3 packaging extractables, degradants,4 etc. The presence of such impurities could pose risks to the safety of the general public, and thus their levels need to be controlled according to International Conference on Harmonization (ICH) guidelines.5-8 Impurity analysis and control are the key activities in process analytical development, and thus adequate analytical methods are needed for the accurate determination of those impurities.9 Some API impurities, however, are so polar that they cannot be retained on the conventional reversed-phase high-performance liquid chromatographic (RP-HPLC) columns; therefore their analyses constitute a real challenge to the analytical community. Research has been devoted to the development of general strategies for the accurate analysis of very polar analytes. For instance, some polar compounds containing reactive functional groups such as hydroxyl and amino can be analyzed after chemical derivatization to reduce the polarity.10 Some polar analytes are charged, therefore ion chromatography or capillary electrophoresis has been used for their analysis. Nonetheless, the application of these methods has been limited because of the relatively poor reproducibility, complexity in method development, and the limitation in choosing detection methodologies.
