Practical purification of hydrophilic fragments and lead/drug-like molecules by reverse phase flash chromatography: tips, tricks and contemporary developments.

Practical purifications of hydrophilic fragments and lead/drug-like molecules are reviewed, focussing particularly on the rational use of C-18 reverse phase flash chromatography by exploiting the relationship between retention time and distribution coefficients. Logical process changes have been implemented to suit the particular physical properties of individual molecules, notably, various combinations of dry loading, methanol-buffer gradients, pH control and columns designed for 100% aqueous elution. These have been used to great effect; facilitating effective, predictable and scalable purifications of fragments and lead/drug-like molecules, for which other techniques sometimes fail.