RP-HPLC法测定琥珀酸曲格列汀的有关物质及酸降解杂质的LC-MS/MS分析  

Determination of related substances in trelagliptin succinate by RP-HPLC and identification of impurities from acid degradation by LC-MS/MS

作　　者：邓思思[1] 李喆宇[1] 江洁滢 王宇驰 张静霞[1] 张春然[1] 徐明琴[1] 唐克慧[1] 

机构地区：[1]成都大学四川抗菌素工业研究所,成都610052

出　　处：《中国新药杂志》2016年第2期226-231,共6页Chinese Journal of New Drugs

摘　　要：目的：建立高效液相色谱法测定曲格列汀的有关物质,并对酸降解产生的主要杂质进行了结构推证。方法：采用sepax C18色谱柱（250 mm×4.6 mm,5μm）;流动相A为0.05 mol·L^-1乙酸铵缓冲盐,流动相B为乙腈,梯度洗脱;检测波长为230 nm;流速为1 m L·min^- 1;柱温30℃;曲格列汀样品进样量为20μL。ESI电离源,负离子模式。结果：在该条件下曲格列汀和各有关物质峰分离良好;琥珀酸曲格列汀在0.001-2 mg·m L^-1浓度范围内（r=0.999 9,n=6）,浓度和峰面积呈良好的线性关系;本法的定量限（S/N=9）为0.3μg;检测限（S/N=3）为0.1μg;解析出酸破坏后主要增加杂质结构为2-[（3-甲基-2,4,6-三氧代四氢嘧啶-1（2H）基）-甲基]-4-氟苯甲腈。结论：本方法简便、准确、灵敏、可靠,能有效测定琥珀酸曲格列汀中有关物质的含量。Objective： To establish an HPLC method for the determination of related substances in trelagliptin succinate,and identify the main impurities from acid degradation. Methods： The separation was performed on a sepax C18column（ 250 mm × 4. 6 mm,5 μm）. Mobile phase A was 0. 05 mol·L^-1ammonium acetate buffer solution,and mobile phase B was acetonitrile. Gradient elution was performed at a flow rate of 1. 0 m L·min^- 1. The detection wavelength was 230 nm. The column temperature was maintained at 30 ℃. The injection volume was20 μL. The ionization source was ESI,and negative ion mode was used for detection. Results： Trelagliptin succinate was completely separated from related substances; the linear range of the method was 0. 001 ~ 2 mg·m L^-1with a correlation coefficient of 0. 999 9. The limit of detection was 0. 1 μg. The limit of quantitation was 0. 3 μg. The structure of the acid destroyed product was 2-[（ 3-methyl-2,4,6-oxo-tetrahydro-pyrimidin-1（ 2H） yl）-methyl]-4-fluorobenzonitrile. Conclusion： This method is simple,sensitive,selective and reliable,and can be used for the determination of related substances of trelagliptin succinate.

关 键 词：琥珀酸曲格列汀 有关物质 梯度洗脱 LC-MS/MS 

分 类 号：R977.1[医药卫生—药品]