Simultaneous on-line characterization of small organic molecules derived from combinatorial libraries for identity, quantity, and purity by reversed-phase HPLC with chemiluminescent nitrogen, UV, and mass spectrometric detection

被引:94
作者
Taylor, EW [1 ]
Qian, MG [1 ]
Dollinger, GD [1 ]
机构
[1] Chiron Corp, Chiron Technol, Small Mol Drug Dis, Emeryville, CA 94608 USA
关键词
D O I
10.1021/ac980402d
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
In the ongoing quest for ever more rapid techniques to quantify small organic molecules, we have evaluated a chemiluminescent nitrogen detector (CLND) as a universal quantitation tool for nitrogen-containing molecules. By how injection analysis (FIA) and in conjunction with reversed-phase (RP) chromatography using gradient elution, the CLND produced a linear response from 25 to 6400 pmol of nitrogen that was equivalent for a set of chemically and structurally diverse compounds. Over the entire linear range, the absolute response exhibited an average error of approximately +/-10% among the compounds. In addition, the response was independent of mobile-phase composition. These results demonstrate that the CLND can be used with FIA or on-line with RP-HPLC for rapid and accurate quantitation down to low-picomole levels, using a single external standard. We also used the CLND in combination with a UV detector and a mass spectrometer (MS) during RP-HPLC (LC/UV/N/MS) to characterize several samples containing small organic compounds synthesized by both standard and combinatorial methods, The identity, quantity, and purity of compounds of interest:were assessed from a single HPLC injection of each sample. These results show this technique (LC/UV/N/MS) to be a widely applicable, generic method for the pharmaceutical industry to rapidly identify, quantify, and determine the purity of small organic compounds.
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收藏
页码:3339 / 3347
页数:9
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