Integration of supercritical fluid chromatography into drug discovery as a routine support tool: II. Investigation and evaluation of supercritical fluid chromatography for achiral batch purification

Supercritical fluid chromatography (SFC) has recently been implemented within our analytical technologies department as a purity assessment and purification tool to complement HPLC for isomer and chiral separations. This report extends the previous work to achiral analysis and purification. This internal evaluation explores the potential impact SFC can have on high throughput, batch purification. Achiral methods have been optimised and batches of compounds purified using a retention time mapping strategy. Here the preparative retention time is predicted from a standard calibration curve and fraction windows set to ensure the peak of interest is collected in one of the four available fraction positions. In this contribution, a completely indirect scale up strategy is applied using totally independent analytical and preparative methods. This novel approach allows for fast analytical purity analysis without compromising the ability to scale up to the preparative system. The benefits and limitations of SFC for batch purification are described in comparison to HPLC across a set of standard compounds and a set of 90 research compounds.