Cârcu-Dobrin Melania, Budău Monica, Hancu Gabriel, Gagyi Laszlo, Rusu Aura, Kelemen Hajnal
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, Romania.
SC VimSpectrum SRL, Tîrgu Mureş, Romania.
Saudi Pharm J. 2017 Mar;25(3):397-403. doi: 10.1016/j.jsps.2016.09.007. Epub 2016 Sep 30.
Fluoxetine is an antidepressant, a selective serotonin reuptake inhibitor (SSRI) used primarily in the treatment of major depression, panic disorder and obsessive compulsive disorder. Chiral separation of racemic fluoxetine is necessary due to its enantioselective metabolism. In order to develop a suitable method for chiral separation of fluoxetine, cyclodextrin (CD) modified capillary electrophoresis (CE) was employed. A large number of native and derivatized, neutral and ionized CD derivatives were screened to find the optimal chiral selector. As a result of this process, heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) was selected for enantiomeric discrimination. A factorial analysis study was performed by orthogonal experimental design in which several factors are varied at the same time to optimize the separation method. The optimized method (50 mM phosphate buffer, pH = 5.0, 10 mM TRIMEB, 15 °C, + 20 kV, 50 mbar/1 s, detection at 230 nm) was successful for baseline separation of fluoxetine enantiomers within 5 min. Our method was validated according to ICH guidelines and proved to be sensitive, linear, accurate and precise for the chiral separation of fluoxetine.
氟西汀是一种抗抑郁药，属于选择性5-羟色胺再摄取抑制剂（SSRI），主要用于治疗重度抑郁症、恐慌症和强迫症。由于其对映体选择性代谢，外消旋氟西汀的手性分离是必要的。为了开发一种合适的氟西汀手性分离方法，采用了环糊精（CD）修饰的毛细管电泳（CE）。筛选了大量天然和衍生化、中性和离子化的CD衍生物，以找到最佳的手性选择剂。通过这一过程，选择了七（2,3,6-三-O-甲基）-β-环糊精（TRIMEB）进行对映体鉴别。通过正交实验设计进行析因分析研究，同时改变几个因素以优化分离方法。优化后的方法（50 mM磷酸盐缓冲液，pH = 5.0，10 mM TRIMEB，15°C，+ 20 kV，50 mbar/1 s，在230 nm处检测）成功地在5分钟内实现了氟西汀对映体的基线分离。我们的方法根据ICH指南进行了验证，结果证明对于氟西汀的手性分离具有灵敏性、线性、准确性和精密度。
