Separation and determination of donepezil hydrochloride enantiomers in plasma by capillary electrophoresis

AimTo establish chiral separation method for donepezil hydrochloride (E2020) enantiomers by capillary electrophoresis (CE) and determine the two enantiomers in plasma. Methods Alkalized plasma was extracted by isopropanol-n-hexane (3∶97) and L-butefeina was used as the internal standard. Enantioresolution was achieved using 2.5% sulfated-beta-cyclodextrin as chiral selector in 25 mmol·L^-1 triethylammonium phosphate solution (pH 2.5) on the uncoated fused-silica capillary column (70 cm×50 μm ID). The feasibility of the method to be used as quantitation of E2020 enantiomers in rabbit plasma was also investigated. ResultsE2020 enantiomers were separated at a baseline level under the above condition. The linearity of the response was evaluated in the concentration range from 0.1 to 5 mg·L^-1. The linear regression analysis obtained by plotting the peak area ratio (A_s/A_i) of the analyte to the internal standard versus the concentration (C) showed excellent correlation coefficient (r=0.999 2 for R(-)-E2020, r=0.999 7 for S(+)-E2020) and the equations were A_s/A_i=0.024 2+0.289 2C and A_s/A_i=0.010 8+0.273 7C, respectively. The low limit of detection was 0.05 mg·L^-1. The inter- and intra-day precision (RSD) were all less than 20%. ConclusionCompared with CSP by HPLC, the CE method is simple, reliable, inexpensive and suitable for studying the stereoseletive pharmacokinetics in rabbits.