Chiral separation of alkylamine antihistamines in pharmaceuticals by capillary isotachophoresis with charged cyclodextrin.

Peter Kubacák, Peter Mikus, Iva Valásková, Emil Havránek

Index: Drug Dev. Ind. Pharm. 33(11) , 1199-204, (2007)

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Abstract

Cyclodextrin-mediated capillary isotachophoresis (ITP) in cationic regime of the separation was developed for the separation and quantitation of alkylamine antihistamine dimethindene (DIM) and pheniramine (PHM) enantiomers in various pharmaceutical preparations (capsules, oral drops, gel, granulated powder). Several electrolyte systems of different compositions and pH were examined. The optimized chiral ITP electrolyte system was consisted of 10 mmol/L potassium acetate adjusted to pH 4.8 with acetic acid, containing 4 mmol/L negatively charged CE-beta-CD (chiral selector) as the leading electrolyte with electroosmotic flow (EOF) suppressing additive, 0.2% (w/v) methylhydroxyethylcellulose (m-HEC), and 5 mmol/L beta-alanine as the terminating electrolyte. The proposed electrophoretic method was successfully validated. It was convenient for the sensitive, simple, rapid, and highly reproducible assay of these antihistamine enantiomers. The calibration graphs relating the ITP zone length to the concentration of DIM and PHM enantiomers were rectilinear (r = 0.999) in the range 40.0-200.0 mg/L of each enantiomer. The relative standard deviations (RSD) were 0.75% for DIM(1), 0.63% for DIM(2), 1.05% for PHM(1), and 0.83% for PHM(2) (n = 6) when determining 100 mg/L DIM and PHM, respectively, standard solutions. According to the validation procedure based on the standard addition technique the recoveries were 97.66-98.34%. Good quantitation was obtained in short analysis time (a single analysis took about 12 min). The minimal sample pretreatment and low running costs make the proposed ITP method a good alternative to commonly used analytical methods (CZE, HPLC). The obtained results suggest that the proposed method is suitable for routine assay of dimethindene and pheniramine enantiomers in various pharmaceuticals.