二维超高效液相色谱质谱联用技术测定注射用头孢地嗪钠的杂质谱

目的 建立二维超高效液相色谱质谱联用法研究注射用头孢地嗪钠的杂质谱。方法 一维色谱采用Waters HSS T3 C18(100mm×2.1mm, 1.8μm)；以磷酸盐缓冲液(取磷酸二氢钾0.87g，无水磷酸氢二钠0.22g，加水溶解并稀释至1000mL)为流动相A，乙腈为流动项B，梯度洗脱；柱温：35℃；流速：0.4mL/min；检测波长：215nm；进样量：3μL；二维色谱采用Waters BEH C18(50mm×2.1mm, 1.7μm)；以0.1%甲酸水溶液为流动相A，0.1%甲酸的乙腈为流动项B，切峰后开始B相3min由2%到95%；柱温：35℃；流速：0.4mL/min；质谱采用Xevo G2-XS QTof MS系统，离子源为ESI源，离子源温度：110℃，毛细管电压：3.0KV，雾化器温度：450℃，雾化器流速：800L/h，扫描范围：m/z 100~2000，测定头孢地嗪主要杂质的一级和二级质谱，进行结构解析。结果 采用UPLC梯度洗脱方法可检出多种头孢地嗪异构体、降解杂质和高分子杂质等，检出杂质的个数和总量均较现行法定标准多。结论 本品的杂质在原料合成、制剂分装及运输储藏过程中均可产生，因此，应对原料和制剂生产过程中的关键技术指标和环境条件加以控制。

Study on the impurity profile of cefodizime sodium for injection by two-dimensional UPLC-QTof MS method#br#

Objective To investigate the impurity profile of cefodizime sodium for injection by a two-dimensional UPLC-QTof MS method. Methods One-dimensional chromatographic conditions with Waters HSS T3 column (100mm×2.1mm, 1.8μm) were adopted. Phosphate buffer solution (dissolve 0.87g potassium dihydrogen phosphate and 0.22g anhydrous disodium hydrogen phosphate in water, then dilute to 1000mL) was used as the mobile phase A and acetonitrile as the mobile phase B. The gradient elution was used. The column temperature was 35℃. The flow rate was 0.4mL/min. The detection wave length was 215nm. Two-dimensional chromatographic conditions with ACQUITY UPLC BEH C18 column (50mm×2.1mm, 1.7μm) were adopted. The solution containing 0.1% formic acid was used as the mobile phase A and acetonitrile containing 0.1% formic acid was used as the mobile phase B. The gradient elution was also used and the flow rate was 0.4mL/min. The G2-S QT of MS Xevo system was used for mass spectrometry. The electrospray ionization (ESI) source was used at the positive ion detection model; the temperature of ESI source was 110℃; the capillary voltage was 3.0kV; the nebulizing temperature was 450℃; the scanning range was m/z 100~2,000. The MS spectrums of the main impurities obtained were used for the elucidation of structures. Results The number and amount of impurities detected by UPLC were more than those tested by thestatutory method. The impurity profile consists of cefodizime isomers, degradation impurities and polymer impurities. Conclusion The impurities can originate from the raw material, process of preparation division, and transportation and storage. It is important to control the key technology indicators and the environmental