建立了超高效液相色谱(UHPLC)法测定盐酸溴己新(1)中15种有关物质.采用Zorbax Eclipse Plus C18柱(4.6 mm× 150 mm,3.5 μm),以甲酸铵缓冲液和乙腈(体积比60∶40)为流动相.通过对流动相pH值、缓冲盐浓度、柱温等条件进行考察,确定了最终色谱条件.分别采用本法和药典标准方法对3个厂家的共16批次1原料药和1片进行对比分析,并采用高分辨质谱对发现的未知杂质结构进行初步推断.结果表明,15个己知杂质和主成分分离良好,强制降解后产物对目标峰的分离没有干扰,表明本法专属性良好.所有1原料药和1片中的己知杂质和总杂含量均满足药典要求.通过LC-MS对其中未知单杂进行了分析,推断其可能为2,4-二溴-6-[[甲基-(4-甲基环己基)氨基]甲基]-苯胺.该方法为开展一致性评价研究奠定了基础.
Fast Assays of Related Substances in Bromhexine Hydrochloride and Its Tablets by Ultra High Performance Liquid Chromatography
An ultra high performance liquid chromatography(UHPLC)method was established to determine the fifteen related substances in bromhexine hydrochloride(1).The Zorbax Eclipse Plus C18 column was used,with ammonium formate buffer-acetonitrile(60∶40)as the mobile phase.The final chromatographic conditions were screened out by examining the conditions such as mobile phase pH,buffer salt concentration,and column temperature.The UHPLC method and pharmacopoeia standard method were used to analyze and compare a total of sixteen batches of 1 bulk drugs and 1 tablets from three manufacturers,and high-resolution mass spectrometry was used to preliminarily infer the unknown impurities.The results showed that the fifteen related substances and principal component were well separated,and the products after forced degradation did not interfere with the separation of the target peak,indicating the good specificity of this method.All known impurities and total impurities in 1 bulk drugs and 1 tablets met the requirements of the pharmacopoeia.The unknown impurity was analyzed by LC-MS,and it was inferred that it might be 2,4-dibromo-6-[[methyl-(4-methylcyclohexyl)-amino]methyl]aniline.This method provided a reference for the consistency evaluation of 1.
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