A multiplexed liquid chromatography/mass spectrometry system for early candidate profiling in drug discovery

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Jackson, M.R;Balogh, M.P
AAPS; Toronto; 10th-14th November 2002
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Characterization of the physiochemical properties of drug candidates is an important aspect of determining the future potential of new chemical entities. Recent developments in the use of liquid chromatography to correlate specific physiochemical properties in the drug discovery process. By performing several diverse chromatographic separations simultaneously, a more complete profile of the properties of a new chemical entity can be achieved and used to evaluate the potential of the drug. Methods and Instrumentation: Physiochemical characteristics of a variety of pharmaceutical compounds are measured under several different separation conditions simultaneously using four chromatographic systems each with UV diode array detection and a single mass spectrometer. Three basic parameter are measured. Sample hydrophobicity (Chromatographic Hydrophobicity Index, CHI), partitioning coefficient using immobilized artificial membrane columns(KIAM), and affinity to bonded active sites are correlated to retention on HPLC columns. Preliminary Data: Experiments were performed with drug mixtures and reversed phase columns for determination of hydrophobicity measurements in basic, neutral, and acidic mobile phase conditions. Retention times were correlated to give CHI values for compounds. The analysis was done on a multiplexed system simultaneously and the data was correlated through a software program. The data demonstrates the ability to gather disparate compound properties in a multiplexed high speed fashion suitable for prescreening in a drug discovery environment.

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