摘要
目的分离、测定血浆样品中盐酸多奈哌齐对映体的含量.方法建立高效毛细管电泳法血浆中加入内标L-酒石酸布托菲诺后,碱化并以异丙醇-正己烷（3：97）提取血浆样品,采用未涂层熔融石英毛细管柱（70 cm×50μm ID）,以25 mmol·L^-1磷酸-三乙胺（pH 2.5）为运行缓冲液,2.5%磺化β-环糊精为手性添加剂,进样电压为-20kV,进样时间为15 s,运行电压为-20 kV.对盐酸多奈哌齐对映体进行电泳分离,并进行家兔血浆样品中盐酸多奈哌齐对映体定量分析的方法验证.结果在上述电泳条件下,盐酸多奈哌齐对映体可达基线分离.测得血浆样品中R（-）-多奈哌齐的回归方程为：As/Ai=0.024 2＋0.289 2C,r=0.999 2,S（＋）-多奈哌齐的回归方程为：As/Ai=0.010 8＋0.273 7C,r=0.999 7,线性范围为0.1～5 mg·L^-1,检测限为0.05 mg·L^-1.结论本法与手性柱HPLC法相比,有高效、快速和经济等优点.
Aim 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·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. 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·L^-1. The linear regression analysis obtained by plotting the peak area ratio （As/Ai） 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 As/Ai = 0.024 2 ＋ 0.289 2 C and As/Ai =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%. Conclusion Compared with CSP by HPLC, the CE method is simple, reliable, inexpensive and suitable for studying the stereoseletive pharmacokinetics in rabbits.
出处
《药学学报》
CAS
CSCD
北大核心
2006年第5期471-475,共5页
Acta Pharmaceutica Sinica
关键词
盐酸多奈哌齐对映体
毛细管电泳
磺化β-环糊精
donepezil hydrochloride enantiomers
capillary electrophoresis
sulfated-beta-cyclodextrin
