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

• Published in: Journal of Chromatography A 2018-09, Vol.1568, p.214-221
• Main Authors: Kanizsová, Lívia, Ansorge, Martin, Zusková, Iva, Dubský, Pavel
• Format: Article
• Language: English
• Subjects: Capillary electrophoresis; Enantioseparation; Method validation; Pindolol; Single-isomer cyclodextrin; β-blockers
• ISSN: 0021-9673
• DOI: 10.1016/j.chroma.2018.07.020

•Fast enantioseparation of pindolol by means of capillary elect rophoresis.•Single-isomer OS-γ-CD cyclodextrin used as a selector.•Complexation parameters used for method optimization with newly available software.•Validation in low (tens μg/mL) and high (hundreds μg/mL) concentration ranges.•Quantitative enantioseparation in Visken® pharmaceutical formulations. 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 μg/mL and 4 μg/mL (0.6 μg/mL and 2 μg/mL per enantiomer), respectively. The calibration curves showed good linearity, with a coefficient of determination R2 ≥ 0.999 over a 5 – 55 μg/mL concentration range and over a 50 – 300 μg/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 μg/mL level and lower than 1.5% at 300 μg/mL 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.