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Simulated moving columns technique for enantioselective supercritical fluid chromatography
Authors:Zhang Yingru  Dai Jun  Wang-Iverson David B  Tymiak Adrienne A
Institution:Bioanalytical and Discovery Analytical Science, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Princeton, NJ 08648, USA. yingru.zhang@bms.com
Abstract:This article describes a very useful extension of an unique column switching technique called "Simulated Moving Columns" (SMC) that was previously reported for chiral high performance liquid chromatography (HPLC) (Zhang and McConnell, Journal of Chromatography A 2004;1028:227-238). SMC uses two or three short chiral columns connected in series, and enables the unresolved enantiomers to separate repeatedly and exclusively through each of the columns until sufficient resolution is attained. The technique is significantly enhanced through the use of supercritical fluid chromatography (SFC). The supercritical or near critical carbon dioxide (CO(2)) used in the mobile phase of SFC possesses the properties of a liquid as well as a gas, and usually results in much sharper peaks compared to HPLC. Consequently, by combining SMC with SFC (SMC-SFC), we were able to dramatically increase the number of SMC cycles with significantly less band broadening compared to HPLC. For the first time, an enantioselective SFC separation was demonstrated by increasing the column from the actual 20 cm length to reach a half meter virtual length with remarkably enhanced efficiency. Off-column band broadening resulting from a two-column SMC system was measured, and its impact on the enantioselectivity of SMC-SFC was found to be much less than in SMC-HPLC.
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