Enantioseparation of five racemic N-alkyl drugs by reverse phase HPLC using sulfobutylether-β-cyclodextrin as a chiral mobile phase additive

Analytical enantioseparations of five N-alkyl drugs, fluoxetine hydrochloride, labetalol, venlafaxine hydrochloride, trans-paroxol, and atropine sulfate, were investigated by reverse phase high-performance liquid chromatography with sulfobutylether-beta-cyclodextrin as chiral mobile phase additive. Effects of various factors such as composition of mobile phase, concentration of cyclodextrins, and column temperature on retention and enantioselectivity were studied. Apparent formation constant between methanol, acetonitrile, and sulfobutylether-beta-cyclodextrin were determined to be 2.90 x 10(-3) and 1.00 x 10(-4) L mmol(-1) under 25 degrees C using UV-spectrophotometry. Van't Hoff plots were used to investigate thermodynamic parameters for enantiomers-stationary phase interaction and formation of inclusion complex. Two retention models were employed individually for evaluation of inclusion complexation between five racemates and sulfobutylether-beta-cyclodextrin. The second model with complex adsorption was more accord with the retention behavior of fluoxetine hydrochloride, labetalol, and venlafaxine hydrochloride enantiomers, while the first model was more consistent with the retention behaviors of trans-paroxol and atropine sulfate. In the selected mobile phase, stoichiometric ratio for both of inclusion complex was found to be 1:1.

Automated summary

In this study, reverse phase high-performance liquid chromatography with sulfobutylether-beta-cyclodextrin as chiral mobile phase additive was used to analytically separate five N-alkyl drugs enantiomers. Various factors affecting retention and enantioselectivity were investigated. The results showed that sulfobutylether-beta-cyclodextrin can effectively enhance the separation of enantiomers.