Think of orthogonal flash chromatography as 2D-chromatography where a reaction mixture or natural product extract is purified first with one methodology or solvent gradient then re-purified with a different method or solvent pair in order to remove co-eluting impurities. This is a technique practiced in medicinal chemistry, especially for final compound purification, when the final product is purified first with normal-phase flash followed by reversed-phase prep HPLC.

There are two general flash chromatography techniques...