The accurate determination of compound purity is crucial for characterizing library purity, monitoring the stability of storage compounds, and obtaining meaningful high-throughput screening results. However, current high-throughput techniques for the determination of compound purity are inadequate. We evaluated on-line chromatography detectors, including UVTWC, UV214, and ELSD detectors, in a series of studies of 233 compound mixtures prepared with known compositions. Results indicate that both UVTWC and UV 214 overestimate the minor component in a mixture whereas ELSD underestimates the minor component. An average of UVTWC and ELSD purities gives a more accurate measure of the relative purity for a wide range of compounds in various purity ranges. This technique was applied to 959 compounds from our compound collection to more accurately determine their relative purity.
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