ANYL 407 |
| The separation of chiral molecules is an extensively studied field in pharmaceutical analysis because enantiomers can exhibit different properties in human systems. Regulatory requirements demand the development of separation methods to assure the enantiomeric purity and stability of chiral drugs. Because the separation of these drug molecules often requires extensive method development, the definition of generic separation strategies, i.e. applicable on large sets of structurally diverse compounds and giving separation for most of them, can be very useful. Capillary electrophoresis (CE) and capillary electrochromatography (CEC) were evaluated for their potential as analytical separation techniques to define such separation strategies. CEC combines the properties of both high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Both techniques are characterized by their relative miniaturization, high efficiencies, fast separations, and a high sensitivity when a mass spectrometer is used as detector. The chiral selectors applied were selected because of their broad enantioselectivity, i.e. highly-sulphated cyclodextrins (HS-CD) for CE and polysaccharides for CEC. Three HS-CDs, α, β and γ, and four polysaccharide stationary phases, Chiralcel OD-RH and OJ-RH, Chiralpak AD-RH and AS-RH, were finally selected to define the strategies. The strategies were constructed as decision trees: first a general screening experiment is executed, and depending on the obtained separation, occasional optimizations are performed. The proposed strategies were tested on larger series of acidic, basic, bifunctional and neutral compounds. Enantioselectivity was observed in CEC for more than 80 % of the test set compounds after application of the strategies, while in CE this was more than 90%, indicating their potential in chiral method development. |
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Chiral Separations Made Easy
1:30 PM-5:00 PM, Wednesday, August 22, 2007 BCEC -- 104C, Oral
Division of Analytical Chemistry |