In this study, “Rapid Isolation of a Minor API Impurity Using SFC, HPLC/MS, and SFC/MS“, we present the process of isolating impurities and degradants from batch lots of drug substance using different chromatographic technologies.

Small amounts of any unknown component having a relative abundance in the batch of greater than 0.1% must be isolated for structure elucidation. If synthesis of the compound is intractable, chromatography is often employed to isolate larger amounts for use as reference standard or for in vivo testing.

SFC is a viable and valuable technology for efficient separation of minor components from complex mixtures. However, to do this process efficiently one must have a way to definitively identify the desired minor peak(s). We have found that complex mixtures are most frequently assayed using RP-HPLC, and that a system that couples MS detection to not only the HPLC analysis but also to analytical SFC is a key tool that makes this work possible.