Moussa Bahia A, Youssef Nadia F, Elkady Ehab F, Mohamed Marwa F
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Pharmaceutical Chemistry Department, National Organization for Drug Control and Research, Giza, Egypt.
Chirality. 2019 May;31(5):362-374. doi: 10.1002/chir.23063. Epub 2019 Mar 12.
Economic and enantioselective synchronous fluorescence spectroscopy and high-performance thin-layer chromatography methods have been developed and validated as per ICH guidelines for the separation of zopiclone enantiomers using L-(+)-tartaric acid as a chiral selector, followed by determination of the chiral-switching eszopiclone. Synchronous fluorescence spectroscopy was successfully applied for chiral recognition of R & S enantiomers of zopiclone at ∆λ = 110 nm based on creating of diastereomeric complexes with 0.06M tartaric acid in an aqueous medium containing 0.2M disodium hydrogen orthophosphate. Synchronous fluorescence intensities of eszopiclone were recorded at 296 nm in concentration range 0.2- to 4-μg/mL eszopiclone. High-performance thin-layer chromatography method depends on resolution of zopiclone enantiomers on achiral HPTLC silica-gel plates using acetonitrile:methanol:water (8:2:0.25, v/v/v) containing L-(+)-tartaric acid as a chiral mobile-phase additive followed by densitometric measurements at 304 nm in concentration range of 1 to 10 μg/band of eszopiclone. The effect of chiral-selector concentration, pH, and temperature on the resolution have been studied and optimized for the proposed methods. The cited procedures were successfully applied to determine eszopiclone in commercial tablets of pure and racemic forms. Enantiomeric excess was evaluated using optical purity test and integrated peak area to describe the enantiomeric ratio. Thermodynamics of chromatographic separation, enthalpy, and entropy were evaluated using the Van't Hoff equation. The proposed methods were found to be selective for identification and determination of the eutomer in drug substances and products.
已根据国际协调会议（ICH）指南开发并验证了经济且对映选择性的同步荧光光谱法和高效薄层色谱法，用于使用L-(+)-酒石酸作为手性选择剂分离佐匹克隆对映体，随后测定手性转换后的艾司佐匹克隆。基于在含有0.2M磷酸氢二钠的水性介质中与0.06M酒石酸形成非对映体复合物，同步荧光光谱法成功应用于在Δλ = 110 nm处对佐匹克隆的R和S对映体进行手性识别。在艾司佐匹克隆浓度范围为0.2至4 μg/mL时，在296 nm处记录其同步荧光强度。高效薄层色谱法依赖于在非手性HPTLC硅胶板上使用含有L-(+)-酒石酸作为手性流动相添加剂的乙腈:甲醇:水（8:2:0.25，v/v/v）分离佐匹克隆对映体，随后在艾司佐匹克隆浓度范围为1至10 μg/条带时于304 nm处进行光密度测量。已研究并优化了手性选择剂浓度、pH和温度对分离度的影响，以用于所提出的方法。所引用的程序已成功应用于测定纯形式和外消旋形式的市售片剂中的艾司佐匹克隆。使用旋光纯度测试和积分峰面积评估对映体过量，以描述对映体比例。使用范特霍夫方程评估色谱分离的热力学、焓和熵。所提出的方法被发现对原料药和产品中优映体的鉴定和测定具有选择性。
