HPLC及HPLC-HRMS法分析利奈唑胺葡萄糖注射液中的有关物质

HPLC and HPLC-HRMS Methods for Detection of the Related Substances in Linezolid Glucose Injection

建立了高效液相色谱(HPLC)法测定利奈唑胺葡萄糖注射液中的有关物质,并与高分辨质谱(HRMS)技术联用,推测各有关物质的化学结构和可能来源。色谱柱采用Zorbax SB C18柱(4.6 mm×250 mm,5μm),流动相A为0.1%三氟乙酸溶液,流动相B为0.1%三氟乙酸乙腈溶液,梯度洗脱。流速为1.0 ml/min,检测波长为254 nm,柱温为35℃。结果显示,建立的方法可同时检测利奈唑胺的15种已知杂质,各杂质与药物分离良好,主要已知杂质及利奈唑胺的线性关系良好。采用电喷雾正离子模式下的四级杆-飞行时间联用质谱(Q-TOF MS)对有关物质结构进行解析,解析了注射液中7个含量较高的杂质化学结构。本研究全面、系统地分析了利奈唑胺葡萄糖注射液中的有关物质,方法的灵敏度及专属性均较高,为加强该品种的质量控制提供了研究基础。

A high performance liquid chromatography(HPLC)method was established for the determination of related substances in linezolid glucose injection,and the structure of each related substance was deduced by the combined use of high resolution mass spectrometry(HRMS)technology and HPLC method.The Zorbax SB C18 column(4.6 mm×250 mm,5μm)was used,with the mobile phase A of 0.1%trifluoroacetic acid solution and phase B of 0.1%trifluoroacetic acid acetonitrile solution(gradient elution).The flow rate was 1.0 ml/min,the detection wavelength was 254 nm,and the column temperature was 35℃.The results showed that the established method could simultaneously detect the fifteen known impurities of linezolid,and all of the impurities were separated well from linezolid.A quadrupole-time-of-flight mass spectrometry(Q-TOF MS)in electrospray positive ion mode was used to analyze the structure of related substances,and seven impurities with high content in the injection were deduced.This study analyzed the related substances in linezolid glucose injection comprehensively and systematically,and had high sensitivity and specificity,which provided a research foundation for strengthening the quality control.