The development of a semi-preparatory scale supercritical-fluid chromatograph for high-throughput purification of 'combi-chem' libraries.
A unique separator was developed which allowed automatic separation and peak collection using semi-preparative supercritical fluid chromatography (SFC). A peak detector switched the effluent between waste and special collection cassettes. Up to 50 mg of various solutes were injected onto a 21-mm I.D. Cyano column. The entire flow path was contained and no aerosols were generated. Collection efficiency was as high as 95%. Peak purity was often greater than 99. 9%. Typical run times were less than 10 min. An analytical SFC was used to screen the performance of a wide range of mobile and stationary phases for the elution of more than 60 miscellaneous small drug compounds. The best 'universal' gradient employed 0.4% isobutyl or isopropylamine dissolved in methanol, then mixed from 5 to 55% into carbon dioxide at 10%/min. Flow rate was 50 ml/min. The analytical SFC was shown to be a good predictor of the semi-prep instrumental performance.
Berger
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Berger Instruments, 123A Sandy Drive, Newark, DE 19713, USA.
Fogleman
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K
Staats
T
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Bente
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P
Crocket
I
I
Farrell
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W
Osonubi
M
M
D010129:4-Aminobenzoic Acid / Q000737:chemistry; D000983:Antipyrine / Q000302:isolation & purification; D001549:Benzamides / Q000737:chemistry; D002082:Butylamines / Q000737:chemistry; D002245:Carbon Dioxide / Q000737:chemistry; D002845:Chromatography / Q000295:instrumentation* / Q000379:methods*; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D007099:Imipramine / Q000302:isolation & purification; D000432:Methanol / Q000737:chemistry; D019151:Peptide Library; D011343:Procaine / Q000302:isolation & purification; D011437:Propylamines / Q000737:chemistry; D013997:Time Factors; D062366:para-Aminobenzoates
D001549:Benzamides; D002082:Butylamines; D019151:Peptide Library; D011437:Propylamines; D062366:para-Aminobenzoates; D002245:Carbon Dioxide; C053521:isobutylamine; D011343:Procaine; C037689:benzamide; C041338:4-aminobenzamide; D007099:Imipramine; C035263:2-propylamine; D000983:Antipyrine; D010129:4-Aminobenzoic Acid; D000432:Methanol