苯甲酸阿格列汀中未知杂质的分离与鉴定
Isolation and identification of unknown impurities of alogliptin benzoate
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摘要: 通过硅胶柱色谱法、溶剂提取法及制备液相色谱法等分离分析方法，从苯甲酸阿格列汀的大生产制备过程中分离得到4个新的有关物质，并根据其理化性质采用核磁共振光谱法、高分辨质谱法、傅里叶变换红外光谱法等多种波谱鉴定方法对其进行分析确证。确定了从苯甲酸阿格列汀的合成过程各步骤中所产生的4个有关物质的化学结构，将它们命名为杂质L、M、T、V，这4个杂质均为首次发现的新杂质。本研究对于苯甲酸阿格列汀生产过程中的质量控制和生产工艺的优化具有重要意义。Abstract: By silica gel column chromatography, solvent extraction and preparative high performance liquid chromatography (HPLC), four new related substance were isolated and purified from the mass production and preparation process of alogliptin benzoate. Then it was analyzed and confirmed by various spectrum identification methods such as nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS) and Fourier-transform infrared spectroscopy (FTIR) according to its physical and chemical properties. The chemical structures of the four related substances produced in each step of the synthesis process of alogliptin benzoate were determined, and they were named as impurities L, M, T, and V. These four related substances were new impurities which were found for the first time. The isolation and identification of these impurities are of great importance to the quality control of alogliptin benzoate, and the optimization of manufacturing process.
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[1] Feng J，Zhang Z，Wallace M B，et al. Discovery of alogliptin: a potent，selective，bioavailabe and efficacious inhibitor of dipeptidyl peptidase IV[J]. J Med Chem，2007，50(10):2297-2300. [2] Zhang SF. Approval for marketing of the new diabetes drug，NESINA[J]. Chin Lic Pharm（中国执业药师），2010，12(6):54. [3] Scott L J.Alogliptin: a review of its use in the management of type 2 diabetes mellitus[J]. Drugs, 2010, 70(18):2051-2072. [4] Li RF，Ouyang XY，lv F，et al.Analysis for patents of anti-diabetic dipeptidyl peptidase inhibitors[J]. Chin New Drugs J（中国新药杂志），2015，24(1):8-17. [5] Shen D，Wang ZJ，Xu C，et al.Synthesis of alogliptin benzoate and its preliminary quality control[J]. Central South Pharm（中南药学），2016，14(9):813-816. [6] Lu YT，Yang DY ，Li ZY，et al. Isolation and characterization of related substances in alogliptin benzoate by LC-QTOF mass spectrometric techniques[J]. J Pharm Biomed Anal，2016，128:253-263. [7] Zhang K，Ma PQ，Jing WN，et al. A developed HPLC method for the determination of alogliptin benzoate and its potential impurities in bulk drug and tablets[J]. Asian J Pharm Sci，2015，10:152-158. [8] Zhou XY，Rong R，ZhaoYL，et al. Determination of related substances in alogliptinbenzoate by HPLC[J].J Shenyang Pharm Univ（沈阳药科大学学报），2016，33(6):444-449. [9] Sun ZY，Qiao SQ，Luo ZL，Determination of related substances in alogliptin benzoate raw materials by HPLC [J].J China Pharm（中国药房），2014，25(33)：3141-3143. [10] Shao J，Gao S，Li XX，et al.Determination of alogliptin benzoate and its related substances [J]. J Shenyang Pharm Univ（沈阳药科大学学报），2015，32(10):780-785. [11] Liu ZW，Wu LH，Wang EJ.Synthesis of alogliptin benzoate [J]. Strait Pharm（海峡药学），2011，23(9):214-215.
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