Theoretical evaluation of the advantages and limitations of constant pressure versus constant flow rate gradient elution separation in supercritical fluid chromatography

• A simplified model is given to describe gradient elution in an adiabatic SFC system.
• Constant pressure gradient elution is compared with the classical constant flow rate.
• Switching to a constant pressure gradient elution offers time gains up to 40%.
• Constant pressure gradient elution offers nearly the same selectivity.

This study reports on the possible advantages of switching from constant flow (cF) based gradient elution separations to constant pressure (cP) based ones in Supercritical fluid chromatography (SFC) by means of mathematical models. All the important parameters (e.g. viscosity) were fitted as a function of pressure and mol% methanol in CO2. It is shown that when switching towards a cP approach in SFC, a time gain of 34% at the end of a 0 to 50% methanol in CO2 gradient is expected. Actual analysis time gains depend on the point at which it is evaluated (e.g. up to 41% after the equilibration step). Due to the dependence of retention on density, cF- and cP-mode do not yield the same selectivity even if the same volumetric-based gradient program is used. Because the components experience a higher average pressure in the cP-mode, the apparent retention factor is slightly lower.