Practical Guidelines to Chiral HPLC Separations of Pharmaceuticals

PRACTICAL GUIDELINES TO CHIRAL HPLC SEPARATIONS OF PHARMACEUTICALS 

Rapid Screening Strategies in Normal- and Reversed-Phase Liquid Chromatography 

More than 100 CSPs are commercially available nowadays, which should make the separation of any pair of enantiomers feasible. However, the enantiorecognition mechanisms involved in the chiral recognition between the analytes and the CSPs are complex and therefore the selection of the appropriate CSPs, depending on the structure of the analyte, is a difficult task. A common approach to develop a new enantioseparation is the stepwise trial-and-error approach based on detailed consideration of the enantiorecognition mechanisms between the chiral selector and the analyte, or on the analyst s experience, or on the consultation of literature or databases. However, this approach is time-consuming and often unsuccessful owing to the fact that achieving enantioresolution is often purely empirical 

Another screening strategy using the same type of columns but with normal-phase gradient elution has been proposed by the pharmaceutical group Lilly.In this strategy, each compound is screened on four columns, i.e., Chiralcel OD-H, Chiralpak AD, Chiralpak AS and Chiralcel OJ. An n-hexane/2-propanol and an n-hexane/EtOH gradient elution system are 

FIGURE 8 Separation of fenoprofen and mianserin enantiomers on three different polysaccharide CSPs. Mobile phase 50 mM phosphate buffer pH 2.0 with lOOmM KPF /ACN (60/40), except for mianserin on Chiralcel OJ-R 20mM borate buffer pH 9.0/ACN (60/40). 

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V. PRACTICAL GUIDELINES TO CHIRAL HPLC SEPARATIONS OF PHARMACEUTICALS... 

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