Evaluation of Evaporative Light-Scattering Detector for Combinatorial Library Quantitation by Reversed Phase HPLC

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Abstract
A quantitation study using reversed phase HPLC with UV and evaporative light-scattering detector (ELSD) was conducted on 90 library standards selected from 15 small molecule combinatorial libraries (six standards from each library). This study assessed the quantitation errors using a single calibration curve for rapid purity analysis of combinatorial libraries. The average quantitation error of six standards from one library at 200 μM by UV was 13.4%, 20.6%, and 60.3%, at 214, 220, and 254 nm, respectively. By ELSD, the average quantitation error of these six standards at 200 μΜ was only 7.7%. Applying this ELSD calibration curve to 84 standards from 14 structurally diverse libraries, an average quantitation error of 16.4% was obtained. The average quantitation error of all 90 standards from 15 libraries using 15 calibration curves was 18.5%.