Varying the concentrations of mobile phase solvents during  flash purification chromatography enhances the ability of the technique to effectively isolate the desired compound from reaction by-products and unconsumed reagents.  Choosing how these concentrations will be varied over time has a significant effect on the purity and recovery of desired compounds.

What is the best starting strong solvent %?   What is the ending strong solvent %?  Should the mobile phase concentrations vary gradually in a linear manner or should they vary step-wise or something else altogether?  Most separations are performed once, occasionally a handful of times.  Because of this, spending effort optimizing a gradient is just not very productive unless there are aids in choosing the gradient profile that provides an effective purification with minimum effort.

Software in flash chromatography instruments, makes it simple to create a gradient.  Now, what should that gradient look like?

In this post I compare isocratic, step, and linear gradients and provide some sage advice on choosing among them.

For most synthesis and natural product chemists, flash chromatography is the primary tool for purification and isolation of compounds of interest. Purification methods include flash system defaulted linear gradients (e.g. 0-100%), active gradient modification (on-the-fly) during purification, and unique method creation based one either the chemist’s experience or TLC data (typically a linear gradient). Rarely do chemists work to optimize the purification to maximize target compound purity by employing a step gradient. In this post, I discuss the value optimized step gradients provide chemists.