Comparative assessment of achiral stationary phases for high throughput analysis in supercritical fluid chromatography

• Retention of bases on many silica based columns drifts over time in SFC when cationic additives are present in the mobile phase.
• Changing stationary phase silanophilicity over time was identified as a reason for the drift.
• A nontraditional, comprehensive column ranking system is presented.
• Ranking based on the long-term retention repeatability of basic drugs in ammonium acetate containing mobile phase.

Supercritical fluid chromatography (SFC) using open bed fraction collection is becoming more widely used for purification of diverse collections of compounds for drug discovery. This application requires predictable chromatography on scale up from analytical to preparative conditions. We have discovered that the selectivities of many columns used for SFC change over time when ammonium acetate additive is present in the mobile phase as a result of changes in silanophilic interactions. This makes scale up predictions difficult. To address this challenge we have developed a nontraditional comprehensive column ranking. Our system is based on the long-term retention repeatability of basic drugs in ammonium acetate containing mobile phase. The decreases in retention over time were used as a measure of changing silanophilicity of the stationary phases and became the basis for a column ranking system. This system, along with results for 24 commonly used silica-based columns, is presented in this paper.