A new predictive method development tool to quickly generate optimized preparative gradients for normal or reverse phase flash chromatography is described, allowing rapid method development while alleviating the need for thin layer chromatography (TLC) plates. In the same time it takes to run a single TLC plate, the Flash Focused Gradient Generator tool, a function of PeakTrak® software, on the CombiFlash® NextGen provides added information to propose better preparative method conditions compared to traditional method development using TLC. The resulting optimized Preparative flash column purifications are complete in as little as 6 minutes.

Scouting gradients completed using the Flash Focused Gradient Generator tool can be run on the CombiFlash NextGen using flash columns (in either normal or reverse phase solvent systems and using either bare silica or functionalized stationary phases. Alternatively, results from analytical HPLC (high performance liquid chromatography) scouting gradients can be used as inputs into the tool.

The advantages of this technique include:
- Providing information by quickly exploring the entire polarity range of the solvent system
- Eliminating the need to run multiple single-solvent mixture TLC conditions
- Allowing convenient method development for columns lacking corresponding TLC plates
- Allowing a chemist to predict and confirm whether a compound can successfully be purified using a particular column and a solvent system, or whether higher-resolution preparative HPLC or SFC (supercritical fluid chromatography) is needed.

Examples showing both normal and reverse-phase purification of peptides and small molecules using the Flash Focused Gradient Generator on the CombiFlash NextGen flash purification system using a variety of stationary phases and solvent systems are shown.

Jack Silver

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