Shasun Research Center, 27, Vandalur Kelambakkam Road, Keelakottaiyur, Chennai 600048, India.
J Pharm Biomed Anal. 2011 Jan 5;54(1):208-12. doi: 10.1016/j.jpba.2010.07.018. Epub 2010 Jul 29.
This paper describes identification and characterization of a process-related impurity of meprobamate drug substance observed in HPLC-UV method. Forced degradation studies were carried out under acidic, basic, oxidation, light and thermal conditions to assess the nature of the impurity. The pure impurity was obtained by preparative LC isolation and analyzed by NMR and mass. Structural elucidation by spectral data and formation of this impurity were discussed in detail. The structure of the process-related impurity was established as carbamic acid-2-carbamoyloxymethyl-2-methyl-pent-3-enyl ester (olefin). Also, the relative response factor, linearity, detection limit (DL), quantitation limit (QL) and recovery were determined for meprobamate and the impurity. Good linearity was obtained for the impurity over the concentration range of 0.03-0.20% (w/w) with the coefficient of determination (r(2)) of 0.999. The DL and QL of olefin impurity were 0.0003 and 0.001% (w/w), respectively. The isolated impurity was co-injected with meprobamate sample to confirm the retention time in HPLC.
本文描述了在 HPLC-UV 方法中观察到的苯巴比妥药物中一种与工艺相关的杂质的鉴别和特性。在酸性、碱性、氧化、光照和热条件下进行了强制降解研究，以评估杂质的性质。通过制备 LC 分离获得了纯杂质，并通过 NMR 和质谱进行了分析。通过光谱数据详细讨论了结构阐明和该杂质的形成。该工艺相关杂质的结构被确定为氨基甲酸-2-氨甲酰氧甲基-2-甲基戊-3-烯基酯（烯烃）。还确定了苯巴比妥和杂质的相对响应因子、线性、检测限（DL）、定量限（QL）和回收率。杂质在 0.03-0.20%（w/w）浓度范围内具有良好的线性，相关系数（r(2)）为 0.999。烯烃杂质的 DL 和 QL 分别为 0.0003 和 0.001%（w/w）。分离得到的杂质与苯巴比妥样品一起进行共注射，以确认 HPLC 中的保留时间。
