Impact of Methanol Adsorption on the Robustness of Analytical Supercritical Fluid Chromatography in Transfer from SFC to UHPSFC

[Image: see text] In supercritical fluid chromatography (SFC), the retention of a solute depends on the temperature, density, pressure, and cosolvent fraction. Here, we investigate how the adsorption of the cosolvent MeOH changes with pressure and temperature and how this affects the retention of several solutes. The lower the pressure, the stronger the MeOH adsorption to the stationary phase; in addition, at low pressure, perturbing the pressure results in significant changes in the amounts of MeOH adsorbed to the stationary phase. The robustness of the solute retention was lowest when operating the systems at low pressures, high temperatures, and low cosolvent fractions in the eluent. Here, we found a clear relationship between the sensitivity of MeOH adsorption to the stationary phase and the robustness of the separation system. Finally, we show that going from classical SFC to ultrahigh-performance SFC (UHPSFC), that is, separations conducted with much smaller packing diameters, results in retention factors that are more sensitive to fluctuations in the flow rate than with traditional SFC. The calculated density profiles indicate only a slight density drop over the traditional SFC column (3%, visualized as lighter → darker blue in the TOC), whereas the drop for the UHPSFC one was considerably larger (20%, visualized as dark red → light green in the TOC). The corresponding temperature drops were calculated to be 0.8 and 6.5 °C for the SFC and UHPSFC systems, respectively. These increased density and temperature drops are the underlying reasons for the decreased robustness of UHPSFC.