呋喃妥因肠溶片中有关物质检测及结构分析

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,5 μm),测定硝基糠醛二乙酯的流动相为:磷酸盐缓冲液(取KH₂PO₄ 6.8 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KH₂PO₄ 6.8g,加水500 mL,用磷酸调pH至4.5)-乙腈(90:10),检测波长为365 nm。 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 diacetate,nitrofurazone and substance A in nitrofurantion enteric-coated tablets,and to do structure analysis of common unknown substances by LC-ESI-MS. Methods: A phenomenex C₁₈ column for 5-nitro furfural diacetate determination was adopted 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 diacetate 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 sensitive,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.

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