Peak distortions arising from large-volume injections in supercritical fluid chromatography

• Experimental comparison of mixed- and modifier stream injections in SFC.
• Modelling based analysis of peak-distortions in large-volume injections.
• Possible effect of viscous fingering owing to the introduction of modifier plug.

Preparative separations in supercritical fluid chromatography (SFC) involve the injection of large volumes of the solute. In SFC, the mobile phase is typically high pressure CO2 + modifier and the solute to be injected is usually dissolved in the modifier. Two-types of injection methods, modifier-stream and mixed-stream, are common in commercial preparative SFC systems. In modifier-stream injection, the injection is made in the modifier stream which is later mixed with the CO2 stream, while in the mixed-stream injection, the injection is made in a mixed CO2 + modifier stream. In this work a systematic experimental and modelling study of the two techniques is reported using single-enantiomers of flurbiprofen on Chiralpak AD-H with CO2 + methanol as the mobile phase. While modifier-stream injection shows non-distorted peaks, mixed-stream injection results in severe peak-distortion. By comparing the modelling and experimental results, it is shown that the modifier “plug” introduced in the mixed-stream injection is the primary cause of the peak distortions. The experimental results also point to the possible existence of viscous fingering which contributes to further peak distortion.