Amylose-based Columns Research Articles

Direct resolution of a new antifungal agent, voriconazole (UK-109,496) and its potential impurities, by use of coupled achiral-chiral high-performance liquid chromatography

Coupled achiral-chiral high-performance liquid chromatography (HPLC) with an achiral amino-based column coupled with a chiral amylose-based column has been used for qualitative and quantitative determination of the potential chiral and achiral impurities of Voriconazole (UK-109,496), a new antifungal agent with two stereogenic centres. The effect of the organic mobile-phase modifier, ethanol, was studied. The assay response was linearly dependent on concentration over the range 1.2–40.4 μg for Voriconazole and 2.5–104.0 ng for the impurities. The limit of detection was 2.5 ng for each analyte.

Chiral HPLC Separations of 1-Azabicyclo[2.2.1]Heptan-3-One and 1-Alkoxycarbonylalkyl-Pyrrolidine-3-Carboxylic Acid Alkyl Ester Enantiomers on Polysaccharide-Based Stationary Phases

Chiralcel OD-H, OJ, Chiralpak AD and AS columns were screened for the enantiomeric separation of 1-azabicyclo-[2.2.1]heptan-3-one (5) and 1-alkoxycarbonylalkyl-pyrrolidine-3-carboxylic acid alkyl ester intermediates (1, 2, 3 & 4, see Figure 1 for structures) during the large-scale synthesis of PD 151832. PD 151832 is a highly potent ml subtype selective muscarinic agonist expected to be useful for patients with Alzheimer's disease. Cellulose-based columns such as Chiralcel OD-H and OJ are in general less efficient than amylose-based columns such as Chiralpak AD and AS for separation of these types of compounds. The optimal column for separation of compounds 3 and 5 is a Chiralpak AD column using hexane/2-propanol/diethylamine as mobile phase, while a Chiralpak AS column works the best for compounds 1, 2 and 4 using the same solvent mixture.