SPE Products For Combinatorial Chemistry

In recent years, advances in combinatorial chemistry (CombiChem) have made a tremendous impact on the pharmaceutical industry by dramatically accelerating the drug discovery process. However, for each synthesis a purification step is required to remove the target molecule from reaction by-products and excess reagents. Because many reactions contain polar to moderately polar reagents, by-products, and products that can be selectively extracted with normal phase SPE, modified flash techniques utilizing silica packed SPE hardware have become a routine procedure for purifying solution-phase combinatorial reactions.

Discovery® SPE products offer combinatorial chemists an excellent opportunity for developing a simple and standardized high throughput purification method for their combinatorial libraries.

In normal phase SPE, polar compounds are retained or adsorbed onto the sorbent via polar-polar interactions when loaded in the presence of an organic sample matrix. Provided that the products, by-products, and reagents display varying polarities, choosing solvents with increasing polarity will allow for sequential elution of key compounds. In most combinatorial flash purification techniques, compounds not of interest are retained on the stationary phase. The products are then collected for analysis in the load flow through, or if weakly adsorbed, they can be selectively removed with a subsequent wash step.

Many combinatorial chemistry labs are synthesizing and characterizing extensive drug libraries. Chemists are therefore employing modified flash chromatography techniques in a 96-well SPE format for the purpose of sample clean-up and baseline impurity removal. In many combinatorial chemistry labs, capacity is a primary concern for such applications. In our studies, we have determined the binding capacity of 4-Fluoro-3-nitrobenzoic acid when loaded into a DSC-Si SPE 96-well plate (100mg/well). Our results show that ~12.5mg of the Fluoro compound can be loaded onto 100mg DSC-Si before beakthrough occurs. Breakthrough determination was analyzed via HPLC analysis.