Corona-charged aerosol detection in supercritical fluid chromatography for pharmaceutical analysis

In this paper we describe the coupling of a corona-charged aerosol detector (CAD) to packed column supercritical fluid chromatography (pSFC). The CAD can be coupled to pSFC by connecting the outlet of the back pressure regulator (BPR) directly to the inlet of the detector. To reduce the noise and increase the reproducibility, the transfer line (1 m x 0.25 mm i.d. stainless steel) was placed in a thermostatic bath at 45 degrees C. Limits of detection (LODs) ranged from 3 to 11.5 ng loaded on column, with an average value of 4.5 ng (from 0.6 to 2.3 mg/L, with an average value of 0.9 mg/L for 5 mu L injection). To reduce differences in response at different mobile-phase compositions, mobile-phase flow compensation was performed by placing a T-piece before the BPR. In this way, the differences in response were significantly reduced from a factor of 2-3 to a factor of 1.2-1.7. Compared to CAD application without flow compensation, the average LOD was higher by a factor of similar to 1.8. However, the nearly uniform response in gradient analysis with mobile-phase flow compensation far outweighed the slight increase in the LOD. The performance of the pSFC-CAD combination was illustrated by the analysis of selected pharmaceutically related compounds. In addition, a comparison with UV detection was made. Measurement of analytes at a relative concentration of 0.05% versus the main component was demonstrated.