Just-in-time purification: an effective solution for cherry-picking and purifying active compounds from large legacy libraries.

Many companies possess a compound collection consisting of purified compounds and of unpurified products from combinatorial libraries. Using commercial and proprietary compounds as examples, this report provides clear examples of the significant impact purification can have on the activity observed for a compound and highlights the need to retest the purified compounds prior to creating structure-activity relationships. Crude mixtures made with commercial compounds led to an increase in the number of false positives in the SXR-GAL4 assay as compared with their pure and purified counterparts.

A novel method for immediate post-purification purity determination of fractions collected during high-throughput purification.

Following purification, the fractions of purified samples typically are analyzed to determine the relative purities of each fraction. We report a novel technique for performing post-purification analysis immediately after each preparative LC/MS run. The Single Pass Compound Purification and Analysis System (SPACPASS) samples and stores a representative aliquot from the fraction while it is being collected.

Purifying the masses: integrating prepurification quality control, high-throughput LC/MS purification, and compound plating to feed high-throughput screening.

In this paper we report using a parallel, four-channel HPLC/MUX/MS purification system, the Purification Factory, to purify thousands of compounds destined for high-throughput screening in a single month. The maximum sample throughput during this 20-workday month was 704 samples/day. Since this purification throughput exceeded the postpurification sample and data handling capabilities provided by commercial solutions, a custom-integrated solution was designed to address these shortcomings.