Simultaneous enantioseparation of antiparkinsonian medication Rotigotine and related chiral impurities by capillary zone electrophoresis using dual cyclodextrin system.

摘要

A dual cyclodextrin (CD) system consisting of sulfated beta-CD (S-beta-CD) and methyl-beta-CD (M-beta-CD) modified capillary zone electrophoresis (CZE) method was proposed to separate the antiparkinsonian drug Rotigotine ((-)-(S)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin) and related chiral impurities (2-(N-propylamino)-5-hydroxytetralin, 2-(N-propylamino)-5-methoxytetralin). The method was optimized by varying the CD type, the buffer pH, individual CD concentration of the dual system and the ionic strength of background electrolyte. Under the optimum conditions, i.e. 2% (w/v) S-beta-CD and 2% (w/v) M-beta-CD in 100mM sodium phosphate (pH 2.5) as the running buffer, separation voltage -20 kV, detected at 200 nm and temperature controlled at 20 degrees C, a satisfactory separation of the six analytes was accomplished. The optimized method was validated for specificity, precision, linearity, accuracy and stability using sodium benzenesulfonate as the internal standard. The relative standard deviation for migration time was less than 0.58%, and 3.78% for peak area ratio. The linearity ranged from 0.005 to 0.25 mM. The recovery ranged from 95.9% to 108.3%. The limits of detection and limits of quantification for each enantiomer were 0.003 and 0.01 mM, respectively. This method was utilized for evaluating the chiral purity of five batches of Rotigotine.