Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine, Pharmacy Science and Technology of Tîrgu Mureş, Tîrgu Mureş, Romania.
Department of Analytical Chemistry and Drug Analysis, Faculty of Pharmacy, University of Medicine, Pharmacy Science and Technology of Tîrgu Mureş, Tîrgu Mureş, Romania.
Chirality. 2020 Aug;32(8):1119-1128. doi: 10.1002/chir.23255. Epub 2020 Jun 7.
Citalopram (CIT) is a frequently used modern antidepressant that inhibits selectively serotonin reuptake in the brain. It has a chiral center in its structure and is used in therapy as both racemic mixture and pure enantiomer as its pharmacological effect is almost entirely associated with S-CIT. The aim of this study was the development of a simple and rapid capillary electrophoresis (CE) method for the separation and quantification of CIT enantiomers. To establish the optimum chiral selector, several native and derivatized, neutral, and ionized cyclodextrins (CDs) were examined at different pH levels. An experimental design strategy was adopted for method optimization; a fractional factorial design was applied for screening purposes to identify significant experimental factors followed by a face-centered central composite design used for optimization purposes. Computational modeling was used to obtain information on the interaction energy and the geometry of the complexes to aid in the understanding of chiral separation mechanism. The best results were obtained when using a 25-mM phosphate buffer at pH 7.0, 3-mM CM-β-CD as chiral selector, 17.5°C temperature, 15-kV voltage, and 50 mbar/s hydrodynamic injection. The separation time was fast, below 3 min, and the migration order was S-CIT followed by R-CIT. The analytical performance of the method was verified in terms of precision, linearity, accuracy, sensibility, and robustness, and the method was applied for the determination of CIT enantiomers from pharmaceutical preparations.
西酞普兰（CIT）是一种常用于抑制大脑中血清素再摄取的现代抗抑郁药。它在结构中具有手性中心，在治疗中既作为外消旋混合物又作为纯对映异构体使用，因为其药理作用几乎完全与 S-CIT 相关。本研究旨在开发一种简单快速的毛细管电泳（CE）方法，用于分离和定量 CIT 对映异构体。为了确定最佳手性选择剂，在不同 pH 值下检查了几种天然和衍生的中性和离子化环糊精（CD）。采用实验设计策略进行方法优化；采用部分因子设计进行筛选，以确定显著的实验因素，然后采用面心中心组合设计进行优化。计算建模用于获取关于相互作用能和配合物几何形状的信息，以帮助理解手性分离机制。当使用 25-mM 磷酸盐缓冲液在 pH 7.0、3-mM CM-β-CD 作为手性选择剂、17.5°C 温度、15-kV 电压和 50 mbar/s 流体动力学进样时，获得了最佳结果。分离时间很快，低于 3 分钟，迁移顺序为 S-CIT 随后是 R-CIT。该方法在精密度、线性、准确性、灵敏度和稳健性方面得到了验证，并应用于从药物制剂中测定 CIT 对映异构体。
