[Separation and determination of donepezil hydrochloride enantiomers in plasma by capillary electrophoresis].
OBJECTIVE
To 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 x L(-1) triethylammonium phosphate solution (pH 2.5) on the uncoated fused-silica capillary column (70 cm x 50 microm ID). The feasibility of the method to be used as quantitation of E2020 enantiomers in rabbit plasma was also investigated.


RESULTS
E2020 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 x 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 x L(_1). The inter- and intra-day precision (RSD) were all less than 20% .


CONCLUSIONS
Compared with CSP by HPLC, the CE method is simple, reliable, inexpensive and suitable for studying the stereoseletive pharmacokinetics in rabbits.
Lu
Yi-Hong
YH
Jiangsu Institute for Drug Control, Nanjing 210008, China.
Zhang
Mei
M
Meng
Qun
Q
Zhang
Zheng-Xing
ZX
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000032:analysis* / Q000097:blood / Q000737:chemistry; D000077265:Donepezil; D019075:Electrophoresis, Capillary / Q000379:methods*; D005260:Female; D007189:Indans / Q000032:analysis* / Q000097:blood / Q000737:chemistry; D008297:Male; D010880:Piperidines / Q000032:analysis* / Q000097:blood / Q000737:chemistry; D011817:Rabbits; D013237:Stereoisomerism; D047392:beta-Cyclodextrins
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D047392:beta-Cyclodextrins; D000077265:Donepezil