Hancu Gabriel, Cârje Anca, Iuga Ileana, Fülöp Ibolya, Szabó Zoltán-István
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Târgu Mureş, Romania.
Department of Analytical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Târgu Mureş, Romania.
Iran J Pharm Res. 2015 Spring;14(2):425-33.
Carvedilol is administered as a racemic mixture of the R(+)- and S(-)-enantiomers, although it was demonstrated that the two enantiomers exhibit different pharmacological effects and stereoselective pharmacokinetics. The aim of this study was the evaluation of several native and derivatized cyclodextrines as chiral selectors for the separation of carvedilol enantiomers. Stereoselective interactions were observed with four cyclodextrines (β-CD, hydroxypropyl-β-CD, randomly methylated β-CD and sulfobuthyl ether- β-CD). The effects of CD concentration, pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. The method was validated for precision of peak-area response, linearity range and limits of detection and quantification. An efficient stereoselective capillary zone electrophoretic method was developed for the determination of carvedilol enantiomers using a simple 25 mM phosphate buffer at a pH = 2.5 and 10 mM β-CD as chiral selector, resulting in baseline separation of the two enantiomers with sharp peaks and relatively short analysis time. Highly satisfactory results were obtained from the analysis of carvedilol from tablets, indicating that the method is suitable for routine analysis of carvedilol in pharmaceutical products.
卡维地洛是以R(+)-和S(-)-对映体的外消旋混合物形式给药的，尽管已证明这两种对映体表现出不同的药理作用和立体选择性药代动力学。本研究的目的是评估几种天然和衍生化的环糊精作为分离卡维地洛对映体的手性选择剂。观察到与四种环糊精（β-环糊精、羟丙基-β-环糊精、随机甲基化β-环糊精和磺丁基醚-β-环糊精）存在立体选择性相互作用。研究了环糊精浓度、pH值、背景电解质组成、毛细管温度、运行电压和进样参数的影响。该方法针对峰面积响应的精密度、线性范围以及检测和定量限进行了验证。建立了一种高效的立体选择性毛细管区带电泳方法，用于测定卡维地洛对映体，使用简单的25 mM磷酸盐缓冲液（pH = 2.5）和10 mM β-环糊精作为手性选择剂，实现了两种对映体的基线分离，峰形尖锐且分析时间相对较短。对片剂中的卡维地洛进行分析获得了非常满意的结果，表明该方法适用于药品中卡维地洛的常规分析。
