Zhang Hui, Sun Lili, Zou Liang, Hui Wenkai, Liu Lei, Zou Qiaogen, Ouyang Pingkai
School of Pharmaceutical Sciences, Nanjing Tech. University, Nanjing 210009, PR China.
College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech. University, Nanjing 210009, PR China.
J Pharm Biomed Anal. 2016 Sep 5;128:18-27. doi: 10.1016/j.jpba.2016.04.041. Epub 2016 May 10.
A sensitive, selective and stability indicating reversed-phase LC method was developed for the determination of process related impurities of Trelagliptin succinate in bulk drug. Six impurities were identified by LC-MS. Further, their structures were characterized and confirmed utilizing LC-MS/MS, IR and NMR spectral data. The most probable mechanisms for the formation of these impurities were also discussed. To the best of our knowledge, six structures among these impurities are new compounds and have not been reported previously. The superior separation was achieved on an InertSustain C18 (250mm×4.6mm, 5μm) column in a gradient mixture of acetonitrile and 20mmol potassium dihydrogen phosphate with 0.25% triethylamine (pH adjusted to 3.5 with phosphate acid). The method was validated as per regulatory guidelines to demonstrate system suitability, specificity, sensitivity, linearity, robustness, and stability.
建立了一种灵敏、选择性好且具有稳定性指示功能的反相液相色谱法，用于测定原料药中琥珀酸曲格列汀的工艺相关杂质。通过液相色谱-质谱联用仪鉴定出六种杂质。此外，利用液相色谱-串联质谱联用仪、红外光谱和核磁共振光谱数据对其结构进行了表征和确认。还讨论了这些杂质形成的最可能机制。据我们所知，这些杂质中的六种结构是新化合物，此前尚未见报道。采用InertSustain C18（250mm×4.6mm，5μm）色谱柱，以乙腈和20mmol磷酸二氢钾与0.25%三乙胺（用磷酸调pH至3.5）的梯度混合溶液实现了优异的分离效果。该方法按照法规指南进行了验证，以证明系统适用性、特异性、灵敏度、线性、稳健性和稳定性。
