| METHOD |
Another group has developed a set of techniques that make it easier to use LC-MS to purify parallel-synthesis libraries. Effective LC-MS purification conditions can be hard to work out, and generic LC-MS system settings are frequently problematic. This is particularly evident in labs where synthetic chemists carry out their own separations without assistance from chromatographic specialists. Authors have now developed an LC sample-loading technique called "at-column dilution" that aids preparative LC of parallel libraries and a method-optimization protocol that facilitates LC-MS analysis of the library compounds. The at-column dilution technique was adapted in part from an approach reported earlier by Thomas E. Wheat of Waters Corp., Milford, Mass. The two techniques establish specific LC conditions and MS fraction collection parameters for each sample in an automated way, using customized software. Together, they improve chromatographic resolution by about a factor of three, compared to generic or universal prep LC methods, and increase the reliability and effectiveness of the MS analyses.
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