Using single-isomer octa(6-O-sulfo)-gamma-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)-gamma-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 mu g/mL and 4 mu g/mL (0.6 mu g/mL and 2 mu g/mL per enantiomer), respectively. The calibration curves showed good linearity, with a coefficient of determination R-2 >= 0.999 over a 5 - 55 mu g/mL concentration range and over a 50 - 300 mu g/mL 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 mu g/mL level and lower than 1.5% at 300 mu g/mL level. Accuracy ranged from 95 to 103% (106% at LOQ level).
The proposed method was successfully tested on a medical formulation of Visken (R) Sandoz intravenous solution and Visken (R) Teofarma pills for oral use.