HZ08有关物质的色谱-质谱结构鉴定

Identification of the Related Substances in HZ08 by LC-MS Techniques

目的采用色谱-质谱联用技术对HZ08的有关物质进行结构鉴定。方法采用Sapphire C18(4.6 mm×250 mm,5μm)色谱柱,甲醇-甲酸醋酸铵溶液(1 L中含有甲酸1.0 mL和醋酸铵2.0 g)流动相梯度洗脱,对HZ08及其酸、碱、光照破坏的有关物质进行分离;电喷雾正离子化测定各有关物质的一级和二级质谱,进行解析鉴定。结果 HZ08中检测到1个含量超过0.1%的有关物质,酸破坏生成4个主要降解有关物质,碱破坏和光照破坏各生成1个主要降解杂质;并通过联用技术和有机反应机制解析确证它们的结构。结论色谱-质谱联用技术能够有效的鉴定药物有关物质,HZ08有关物质鉴定结果对其质量控制和工艺优化提供了参考依据。

OBJECTIVE To identify the related substances in HZ08 by hyphenated techniques.METHODS A LC-PDA-MS/MS method was developed for the related substances separation and determination.A Sapphire C18（4.6 mm×250 mm,5 μm）.column was used with a mixture of methanol and ammonium acetate buffer solution as the mobile phase with gradient elution.HZ08 and the related substances resulted from acid,alkali,and light stress tests were separated under the established HPLC condition and detected with electro-spray positive ionization MS/MS method.The spectra obtained were used for the structures elucidation.RESULTS Only one related substance was found in HZ08 with the content over 0.1%.Four decomposed substances were found in the acid stress test,one from the alkali and one from the light stress tests.Their structures were elucidated by using the spectra as well as the organic reaction mechanisms.CONCLUSION The hyphenated LC-MS method is useful for the identification of related substances in pharmaceuticals.The related compounds found in HZ08 are valuable for the manufacturing process optimization and quality control of HZ08.