| Abstract
| - An automated high-throughput liquid−liquid extraction(LLE) methodology has been developed and utilized forthe initial purification of the combinatorial library samplescontaining unreacted amines and other water-solublebyproducts or impurities. Various extraction solvents wereevaluated along with different extraction devices. The LLEmethod was automated using 96-well-format plates anda robotic liquid-handling workstation. In the optimizedLLE method, crude combinatorial library samples weredissolved in a water-immiscible organic solvent, butylacetate, and added to each well in a 96-well-format platepacked with an inert support material coated with hydrochloric acid. Separation occurs based on the partitioningof the compounds between two liquid phases. Productrecovery, purity, and amine removal efficiency weredetermined by HPLC with and without precolumn derivatization. The automated method was successfully appliedto the cleanup of some representative combinatoriallibrary samples with greater than 98% amine removal andan average product purity of 90%. The application of theautomated high-throughput LLE method should greatlyreduce the labor, time, and cost associated with thepurification of combinatorial libraries.
|
