Defining a system suitability limit to decide on column deterioration and to facilitate column transfers in chiral...

The separation of enantiomers is an important requirement during the entire drug life cycle in the pharmaceutical industry. High-performance liquid chromatography and supercritical fluid chromatography (SFC) are the main chromatographic techniques used to separate enantiomers. Since chiral stationary phases are often extensively used once a method has been developed, columns will age and must be replaced after a certain period. However, no practical guidelines exist to determine when a column is deteriorated or to decide whether a transfer to another column (with the same chiral selector) is successful. In this study, a system suitability limit for resolution was defined, based on an intermediate (time-different) precision study in SFC on four immobilized polysaccharide-based columns that only differed in manufacturer or particle size. This system suitability limit could be used to decide on column deterioration or as a requirement to evaluate whether a separation transfer was successful. Some method adaptations may be necessary to obtain successful transfers. An approach was proposed, which helped the analyst to make successful transfers. Graphical abstract.