Using single-isomer octa(6-O-sulfo)-γ-cyclodextrin for fast capillary zone electrophoretic enantioseparation of pindolol: Determination of complexation constants, software-assisted optimization, and method validation

Abstract The present study describes a rapid and effective capillary electrophoresis (CE) method for the enantioseparation of pindolol using single-isomer octa(6-O-sulfo)-γ-cyclodextrin. The complexation parameters were determined under neutral and high pH conditions to identify optimal separation conditions using a theoretical model. Baseline separation of pindolol enantiomers was achieved within 6 min in a sodium/MOPS buffer, pH 7.2, with a selector concentration of 6 mM. The method was validated according to the ICH guidelines using imidazole as an internal standard. Low limits of detection and quantification were found, specifically 1.2 μ g / m L and 4 μ g / m L (0.6 μ g / m L and 2 μ g / m L per enantiomer), respectively. The calibration curves showed good linearity, with a coefficient of determination R 2 ≥ 0.999 over a 5 – 55 μ g / m L concentration range and over a 50 – 300 μ g / m L concentration range of the racemic mixture. The relative standard deviations (%RSD) of intra-day and inter-day precision were lower than 8% at LOQ level, lower than 3% at 50 μ g / m L level and lower than 1.5% at 300 μ g / m L level. Accuracy ranged from 95 to 103% (106% at LOQ level). The proposed method was successfully tested on a medical formulation of Visken® Sandoz intravenous solution and Visken® Teofarma pills for oral use.