呋喃妥因肠溶片中有关物质检测及结构分析

Determination and structure analysis of related substances of nitrofurantion enteric-coated tablets

目的:分别建立呋喃妥因肠溶片中硝基糠醛二乙酯和呋喃西林、水解产物杂质A的HPLC测定方法,并采用液质联用技术对共性未知杂质进行结构分析。方法:Phenomenex C18色谱柱(250 mm×4.6 mm,5μm),测定硝基糠醛二乙酯的流动相为:磷酸盐缓冲液(取KH2PO46.8 g,加水500 mL,用磷酸调pH至4.5)-乙腈(50∶50),检测波长306 nm;测定呋喃西林、水解产物杂质A的流动相为:磷酸盐缓冲液(取KH2PO46.8g,加水500 mL,用磷酸调pH至4.5)-乙腈(90∶10),检测波长为365nm。结果:样品中各成分的分离度及检出灵敏度能满足有关物质限度的要求。硝基糠醛二乙酯的检出限为1.5 ng,呋喃西林和杂质A的检出限分别为0.08 ng、0.14 ng。结论:建立的HPLC测定方法灵敏、准确、专属性强,适用于呋喃妥因片中有关物质的测定;采用液质联用技术初步推测出了未知杂质1的结构。

Objective： To develop an HPLC method for the identification of 5 - nitro furfural diaeetate, nitrofurazone and substance A in nitrofurantion enteric - coated tablets, and to do structure analysis of common unknown sub- stances by LC -ESI -MS. Methods：A phenomenex C18 column for 5 -nitro furfural diacetate determination was a- dopted with a mobile phase consisting of phosphate buffer（ adjusted to pH 4.5 with 6. 8 g KH2PO4 added with 500 mL water） - acetonitrile （50： 50）,and the detection wavelength was 306 nm. The mobile phase of nitrofurazone and substance A consisted of phosphate buffer（ adjusted to pH 4. 5 with 6. 8 g KH2PO4added with 500 mL water） - acetonitrile （90： 10）, and the detection wavelength was 365 nm. Results： The resolution and sensitivity of related substances were acceptable. The detected limit of 5 - nitro furfural diaeetate was 1.5 ng, and the detected limits of nitrofurazone and substance A were 0. 08 ng and 0. 14 ng respectively. Conclusion：The method of HPLC is sensi- tive,accurate and specific to be used to determinate the related substances in nitrofurantion tablets;Initial structure of related substance 1 was inferred by LC -ESI- MS.