LCMS-QTOF鉴定卡络磺钠原料药的有关物质

Identification of Related Substances in Carbazochrome Sodium Sulfonate Raw Materials by LCMS-QTOF

关键词:  卡络磺钠  有关物质  四极杆飞行时间质谱  杂质谱

Key words:  carbazochrome sodium sulfonate  related substances  LCMS-QTOF  impurity profile

摘要:

目的 检测卡络磺钠原料药中有关物质，并进行结构鉴定，为工艺优化和质量控制提供参考。方法 采用Shim-pack Scepter C₁₈(4.6 mm×250 mm，5 µm)色谱柱，以50 mmol·L^–1乙酸铵水溶液为流动相A、乙腈为流动相B对卡络磺钠强制降解溶液中的有关物质进行分离。采用四极杆飞行时间高分辨质谱在m/z 100~800内进行正负离子扫描，数据依赖性采集获取二级质谱图。结合有关物质精确质量数、质谱裂解规律及卡络磺钠合成工艺推测其可能的结构。结果 卡络磺钠原料药经强制降解破坏得到8个主要的杂质，2种为已报道杂质，6种为本研究首次报道。强制降解试验表明卡络磺钠对高温和氧化相对较为稳定，光照、强酸和强碱条件对卡络磺钠影响较大。卡络磺钠原料药中检出杂质5，6和8，高温破坏的主要降解产物是杂质8。结论 本研究建立的液相色谱-四极杆飞行时间质谱联用法具有良好的分离能力，可有效地鉴定卡络磺钠原料药中有关物质，为其生产工艺和质量控制提供了参考。

Abstract:

OBJECTIVE To detected the related substances in carbazochrome sodium sulfonate and indentified structure to provide reference for process optimization and quality control. METHODS The separation of related substances in forced degradation solution of carbazochrome sodium sulfonate was carried out by using a Shim-pack Scepter C₁₈(4.6 mm×250 mm, 5 µm) with 50 mmol·L^-1 ammonium acetate solution as mobile phase A and acetonitrile as mobile phase B. MS was performed on quadrupole time of flight high-resolution mass spectrometry under positive and negative mode with the mass range of m/z 100-800, MS² was acquired under data dependent acquisition mode. Combined with the exact molecular mass, fragmentation rule and synthesis process, the possible structures of related substances were deduced. RESULTS Eight major impurities were found in carbazochrome sodium sulfonate degradation solutions. Among the identified impurities, 2 were reported and 6 were firstly reported. The force degradation test proved that carbazochrome sodium sulfonate was relatively stable on high temperature and oxidation conditions, while light, strong acids and strong alkali had a greater impact on carbazochrome sodium sulfonate. Related substances 5, 6 and 8 were detected in carbazochrome sodium sulfonate raw materials. Impurity 8 was the main degradation impurity by high temperature. CONCLUSION HPLC method combined with flight high resolution mass spectrometry established in this study has good separation and identification of related substances in carbazochrome sodium sulfonate, which provides a reference for its production process and quality control.