In preparative chromatography the goal is to isolate a large quantity of organic target molecules during each run. A high sample mass per injection can be achieved by using a high sample concentration, a large injection volume, or a combination of both. Often preparative samples are dissolved in pure organic solvents. In contrast, the initial gradient start conditions usually contain a high percentage of water and a corresponding low percentage of organic solvent. Therefore the sample plug is often poorly compatible with the initial mobile phase. This reduces the mass loading capacity and causes chromatographic issues, e.g., sample precipitation, blocked capillaries and frits, disturbance of column equilibrium, and bad peak shapes.

Dionex demonstrates how the deficiency of a limited mass loading capacity can be overcome by using adaptable and sophisticated sample injection procedures. By using different combinations of organic solvents for sample dissolution and additional solvent and air plugs (sandwich injection) we increased the amount of sample per injection and reduced chromatography disturbances. Further benefits of this procedure are higher sample throughput and reduced cost of consumables, e.g., solvents and preparative columns.

Preparative LC Challenges

Preparative chemists face many demands in their day-to-day work. These include:

• Reliability and robustness of chromatography (e.g. peak drift)
• Ease of use (it can be difficult to define fraction collection parameters)
• Safety issues (handling of large solvent volumes)
• Sample and fraction storage formats
• Fractionation of unresolved peaks
• Optimized recovery and purity
• Large number of samples