I'm once again curious on a broad topic, but with a specific application. I need to separate two compounds with very similar retention times (one which absorbs UV, one very weakly colored - ie, impossible to see until fractions concentrated) Eluting with 2% MeOH in CH2Cl2, by flash chromatography gave the products as a mixture across 5 mL fractions, #123-150 (UV active product slightly ahead of weakly colored impurity).
My first thought is to increase column length, decrease MeOH to 1% and not use an accelerated flow rate, but that will take forever and I'm impatient. I suppose I could also try a different solvent system, but without being able to visualize the impurity, it will be hard to guage the likely success of any variation. So I considered pHPLC, and prep TLC, (neither of which will see the impurity) and now I'm wondering about the relative resolution of these (and other) common chromatography methods. Since I didn't find a comprehensive list using google or the search function, does anyone have any additions or edits to this short list?
pHPLC >> column chrom. > reverse phase column > flash chromatography > pTLC