title: Development and validation of a separation method for the diastereomers and enantiomers of aziridine-type protease inhibitors.
abstract: Aziridine derivatives are attracting pharmacological interest as protease inhibitors. Due to their two centers of chirality, the aziridines studied here are mixtures of two diastereomers and corresponding enantiomers. Applying cyclodextrin-modified capillary electrophoresis resulted in a baseline separation of the four isomers. The most robust separation was obtained by means of 2 mM sulfated beta-cyclodextrin in 50 mM phosphate buffer of pH 2.5. Using this method, 0.25% of the trans-diastereomers aziridine could be precisely and accurately quantified in the presence of 99.75% of the cis-isomers. The corrected peak-area ratios, migration times, and resolutions were found to be robust with respect to small variations of voltage, buffer concentrations, pH, temperature, chiral selector concentration, and different lots.
authors.affiliation: Institute of Pharmacy and Food Chemistry, University of Würzburg, Würzburg, Germany.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Bitar
authors.forename: Björn
authors.initials: B
authors.lastname: Degel
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
mesh_terms: D001388:Aziridines / Q000302:isolation & purification*; D019075:Electrophoresis, Capillary / Q000379:methods*; D011480:Protease Inhibitors / Q000302:isolation & purification*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D001388:Aziridines; D011480:Protease Inhibitors