Increasing Production Rate of Basic Compounds by Performing Preparative Chromatography at High pH

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Cecilia Mazza, Jeff Mazzeo, Ziling Lu, Tom Sirard, Uwe Neue
HPLC 2002; Montreal; 3-4 June 2002
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Reversed-phase chromatography of basic compounds has traditionally been performed at acidic pH to minimize secondary interactions and improve peak shape. In the last decade, the advent of higher purity silica and improved bonding technology has permitted the use of more neutral pH for basic compounds. The latest advance has been the development of hybrid particle packings that allow chromatography at high pH with good column lifetime. We have recently found that running preparative chromatography of basic compounds at high pH leads to substantial gains in loadability compared to running at neutral or acidic pH. In particular, converting the solutes to neutral species permits at least 50 times higher loadability, such that 500 mg can be loaded on a 19 X 50 mm column. The implications of these results are addressed.

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