2D-LC-IT-TOF/MS法鉴定注射用头孢替唑钠未知杂质3的结构

Structure Identification of Unknown Impurity Ⅲ in Ceftezole Sodium for Injection by 2D-LC-IT-TOF/MS

目的:应用在线脱盐-高效液相色谱-离子阱-飞行时间质谱(2D-LC-IT-TOF/MS)法对注射用头孢替唑钠在药典条件下检出的未知杂质3结构进行分析。方法:1stD-LC色谱条件:Inert Sustain^(TM)C_(18)(250 mm×4. 6 mm,5μm)色谱柱,枸橼酸溶液(取枸橼酸3 g,加水溶解并稀释至900 ml)-乙腈(90∶10)为流动相进行等度洗脱; 2ndD-LC色谱条件:Inert SustainTMC18(50 mm×2. 1 mm,2μm)色谱柱,0. 1%甲酸-乙腈(85∶15)为流动相进行等度洗脱;质谱条件:ESI正离子检测,雾化气流速1. 5 L·min^(-1),干燥气流速10 L·min^(-1),脱溶剂管温度200℃。根据多级质谱信息来推定药典条件下检出的未知杂质3结构。结果:药典方法下,注射用头孢替唑钠中共检出3个有关物质,推定出其中1个含量大于0. 1%的有关物质的结构。结论:建立的方法可用于注射用头孢替唑钠中杂质的鉴定,为注射用头孢替唑钠的质量控制与工艺优化研究提供可靠的保证。

Objective: To rapidly identify the impurity Ⅲ in ceftezole sodium for injection by 2D-LC-IT-TOF/MS. Methods: For the 1stD-LC,the chromatography was carried out on an Inert SustainTMC18 (250 mm × 4. 6 mm,5 μm) column and the mobile phase of citric acid solution (taking 3 g citric acid,adding water to dissolve and dilute to 900 ml)-acetonitrile (90 ∶ 10),and for the 2ndDLC,an Inert SustainTMC18 (50 mm × 2. 1 mm,2 μm) column was used with 0. 1% formic acid-acetonitrile (85 ∶ 15) as the mobile phase with gradient elution. Electrospray ionization (ESI) source was tested in positive ion modes. The nebulized gas flow was 1. 5 L· min-1. The dry gas flow was 10 L· min-1. The desolvent tube temperature was kept at 200 ℃. The related substances were characterized according to multi-level MS behaviors. The 2D-LC-IT-TOF/MS method was employed to identify the structures of the impurityⅢ from ceftezole sodium for injection. Results: A total of three related substances were detected out from ceftezole sodium for injection. One of them was identified the structure. Conclusion: The established method is suitable for the rapid identification of impurities in ceftezole sodium for injection,which can be applied as a useful analytical tool for the quality control and preparation process optimization of ceftezole sodium for injection.