苯溴马隆及其杂质的质量研究

Studies on the Quality of Benzbromarone and Its Impurities

建立了用HPLC和TLC两种方法测定新药苯溴马隆的杂质限量 ,以确保药物的质量。用反相HPLC法 ,ODS柱 ,甲醇 水 冰醋酸 (88∶1 2∶2 .5 ) (pH 3 .5 )为流动相 ,检测波长 2 5 4nm ,流速 1 .0mL min ,分离出两种主要杂质 ,其结构已确证 ,在国内外文献中均未见报道。在制定苯溴马隆质量标准时 ,已将所建立RPHPLC法 ,作为该药物有关物质的测定方法。

Benzbromarone is a new drug for treatment of gout disease. This article described the study on the quality standard of benzbromarone which was synthesized by ourself. The content of benzbromarone and its impurities were determined by reversed phase high performance liquid chromatography (RPHPLC) on an ODS column using MeOH-H2O-HAc(88:12:2.5)(pH 3.5) as mobile phase. The flow rate was 1.0 mL/min, and the detection wavelength was at 254 nm. The main impurities C and D were separated from rough benzbromarone. The related substances were determined by thin layer chromatography (TLC) using silica gel-CMC plat. The impurity C was checked by TLC using three different developing solvents. Experiments showed that the material and the tablet of benzbromarone were rather stable because their impurities were not increasing, and the impurities C and D were by-products during synthesis and were not degradation products. They were two new components, e.i. 3-(3-bromo-4-hydroxy) benzoyl-2-ethyl-benzofuran and 3-2',3',5',5-tetrabromo-4'-hydroxy-benzoyl-2- ethyl-benzofuran, respectively. The HPLC and the methods for determining related substances in this article have been used as standard methods in quality standard of benzbromarone.