盐酸吡格列酮主要杂质在溶液中的顺反式异构化研究

Geometrical Transformation of the Major Impurity of Pioglitazone Hydrochloride in Solution

用反相高效液相色谱法检测盐酸吡格列酮中主要杂质吡格烯在溶液中的 Z- E异构体的转化情况 ,同时利用核磁共振和液 -质联用确证转化物的结构。采用十八烷基键合硅胶色谱柱 ,以乙腈 -水 -醋酸 (5 0 0∶ 5 0 0∶ 0 .9,用氨试液调至 p H6 .0± 0 .0 5 )为流动相 ,检测波长 2 2 5 nm ,以归一化法计算异构体含量。光照条件下吡格烯在溶液中存在Z- E式异构体的转化且能达到一定的平衡 ,但在避光操作时吡格烯的转化不影响盐酸吡格列酮中有关物质的测定。

Geometrical transformation of 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzylidene]-2,4- thiazolidione (2), the major impurity of pioglitazone hydrochloride (1) in solution was studied by HPLC, NMR and LC-MS. A C 18 column was used, with mobile phase of acetonitrile-water-acetic acid (500∶500∶0.9, pH6.0±0.05, adjusted with ammonium hydroxide), at detection wavelength of 225 nm. The content of Z-2 and E-2 were determined with normalization method. The results showed that Z-2 and E-2could transform and balance in the solution by irradiation. But there had no interference to the determination of 2 in 1 in light-tight condition.