盐酸特拉唑嗪有关物质的色谱-质谱结构鉴定

目的: 采用色谱-质谱联用技术对盐酸特拉唑嗪有关物质进行结构鉴定. 方法: 采用Sepax GP-C₈(250 mm×4.6 mm,5 μm)色谱柱,以醋酸铵缓冲液(1 L中含醋酸铵4.0 g,以甲酸调pH至3.2)-乙腈(1685:315)流动相等度洗脱,对盐酸特拉唑嗪有关物质进行分离;采用电喷雾正离子化的四极杆飞行时间质谱(LC-Q-TOF/MS)方法测定离子准确质量并分析子离子特征,结合对照品对照确证有关物质结构.质谱电喷雾正离子化的喷雾电压3 kV、雾化氮气压力150 kPa、气流量6 L·min^-1、温度180 ℃. 结果: 在所建立的条件下,盐酸特拉唑嗪与其有关物质分离良好,检测出14个有关物质,并综合分析鉴定了有关物质结构,它们大都具有4-氨基-6,7-二甲氧基喹唑啉母核结构,制剂中有关物质状态与原料药中的相似. 结论: 色谱-质谱联用技术能有效地鉴定盐酸特拉唑嗪有关物质,为其工艺和质量控制提供参考依据.

Objective: To identify the related substances in terazosin hydrochloride by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(LC-Q-TOF/MS)technique. Methods: A Sepax GP-C₈ column(250 mm×4.6 mm,5 μm)was used for the separation of the related substances with a mixture of acetonitrile and ammonium acetate buffer solution adjusted to pH 3.2 with formate(1685:315, v/ v)as the mobile phase by isocratic elution.The structures of the related substances were speculated by electrospray positive ionization LC-Q-TOF/MS for accurate ion mass determination and elucidation,and verified further by reference substances and spectroscopic analysis.The conditions of LC-Q-TOF/MS were as follows:the spray voltage 3 kV,the nitrogen draying gas nebulizer pressure 150 kPa,the flow rate 6 L·min^-1,the gas temperature 180 ℃. Results: Terazosin hydrochloride and the related substances were separated under the established HPLC condition.Fourteen related substances in terazosin hydrochloride were characterized by the hyphenated technique with most of them as derivatives with the same frame structure of 4-amino-6,7-di methyquinazolin.The impurity profiles for the preparations were similar with the API. Conclusion: The hyphenated LC-MS method is useful for the identification of related substances in terazosin hydrochloride.The results obtained are valuable for its manufacturing process and quality control.

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[11] EP 7.0[S].2010:3045
[12] USP 34-NF 29[S].2010:4360