Analytical & Separation Services, Daicel Chiral Technologies (India) Pvt Ltd, Survey No. 542/2, IKP Knowledge Park, Turkapally, Shamirpet Mandal, Medchal-Malkajgiri District, Hyderabad-500101, Telangana, India.
Department of Chemistry, University college of science, Osmania University campus, Hyderabad-500007, Telangana, India.
J Chromatogr Sci. 2022 Mar 23;60(3):250-259. doi: 10.1093/chromsci/bmab075.
A selective, sensitive and robust chiral analytical method was developed for the quantification of Brivaracetam (BRV) and its three isomers. Systematic chiral chromatographic elution process was executed in different modes on chiral columns of polysaccharide based to attain the finest condition. The analytical method was developed by utilizing immobilized polysaccharide chiral column (CHIRALPAK IG-U) with reversed phase under isocratic condition containing acetonitrile and 10 mM ammonium bicarbonate in the proportion of 40:60 (v/v). The mobile phase flow rate and column temperature were monitored at 0.3 mLmin-1 and 25°C with a resolution of more than 2.0. The eluted components from the column were processed at 212 nm UV detection. The limit of detection and limit of quantification values of BRV, 2R, 4S-Isomer, 2R, 4R-Isomer and 2S, 4S-Isomers were found to be 0.0066/0.02, 0.0035/0.0107, 0.0036/0.0109 and 0.005/0.0152 µgml-1 respectively. Precision, linearity, accuracy and robustness were conducted according to ICH guidelines and the findings were within the acceptable limits. The proposed analytical method was found to be precise, accurate and specific for the quantification of enantiomer and its diastereomers for drug product and drug substance of BRV.
建立了一种选择性、灵敏且稳健的手性分析方法，用于定量分析布瓦西坦（BRV）及其三种异构体。在多糖手性柱上以不同模式进行系统的手性色谱洗脱过程，以达到最佳条件。该分析方法是通过利用固定相多糖手性柱（CHIRALPAK IG-U）在反相条件下，以 40:60（v/v）的比例含有乙腈和 10 mM 碳酸氢铵的等度条件下开发的。监测流动相流速和柱温为 0.3 mLmin-1 和 25°C，分辨率大于 2.0。从柱上洗脱的组分在 212nm UV 检测下进行处理。BRV、2R、4S-异构体、2R、4R-异构体和 2S、4S-异构体的检测限和定量限分别为 0.0066/0.02、0.0035/0.0107、0.0036/0.0109 和 0.005/0.0152 µgml-1。根据 ICH 指南进行了精密度、线性、准确性和稳健性研究，结果均在可接受范围内。该分析方法被证明可用于定量分析 BRV 及其对映异构体和非对映异构体的药物产品和药物物质，具有精确、准确和特异性。
