Determination of salbutamol enantiomers by high-performance capillary electrophoresis and its application to dissolution assays

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 16; no. 2; pp. 357 - 366
• Main Authors: Esquisabel, Amaia, Hernández, Rosa M, Gascón, Alicia R, Igartua, Manoli, Calvo, Begoña, Pedraz, José Luis
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.10.1997; Elsevier Science
• Subjects: Adrenergic beta-Agonists - analysis; Albuterol - analysis; Analysis; Biological and medical sciences; Capillary electrophoresis; Chiral separation; Cyclodextrins; Cyclodextrins - chemistry; Electrophoresis, Capillary - methods; General pharmacology; Hydrogen-Ion Concentration; Medical sciences; Pharmacology. Drug treatments; Reproducibility of Results; Salbutamol; Validation; Validation; Cyclodextrins; Salbutamol; Capillary electrophoresis; Chiral separation; Capillary column; Zone electrophoresis; Enantioselectivity; Bronchodilator; Oligosaccharide; Dissolution; In vitro; Separation method; Cyclodextrin; Detector; Enantiomer; Dosage form; Active ingredient; Diode array; Tablet; Inclusion compound; Release; Quantitative analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/S0731-7085(97)00047-2

Capillary zone electrophoresis was successfully applied to the chiral separation of salbutamol after addition of a suitable cyclodextrin chiral selector to the electrophoresis buffer. Parameters important in achieving enantiomeric separation are cyclodextrin type, mobile phase pH and applied field strength. In our study, salbutamol enantiomeric separation was obtained with the following conditions: heptakis (2,6-di- O-methyl)- β-cyclodextrin in 40 mM Tris (pH 2.5) and at 15 kV, obtaining a 3.09 resolution with migration times of 13.74 min for ( R)-salbutamol and 13.98 min for ( S)-salbutamol. Linearity, limit of quantitation, precision and accuracy were established using this method. The calibration curve was linear in a range of 1–40 μg ml −1 of racemic salbutamol (0.5–20 μg ml −1 of each enantiomer). This method was applied to evaluate the enantioselective release of salbutamol and taking into account the hypothesis that one enantiomer of a chiral drug would be released faster than the other from a pharmaceutical dosage form containing a racemic drug and a chiral excipient. For this purpose, matrix tablets formed by chiral excipients such as hydroxypropylmethylcellulose (HPMC) were considered. The release of the enantiomers of salbutamol from the formulations containing HPMC was found to be equivalent, with constant dissolution values ( K) of 1.187±0.223% min − n for ( R)-salbutamol and 1.076±0.268% min − n for ( S)-salbutamol.