液相色谱-四极杆飞行时间质谱联用法鉴定注射用盐酸吉西他滨中的未知杂质

Identification of Major Impurity in Gemcitabine Hydrochloride for Injection by HPLC-QTOF

目的对注射用盐酸吉西他滨的主要杂质进行结构分析。方法采用液相色谱-四级杆飞行时间质谱联用技术对该杂质进行结构分析,色谱条件:采用ZORBAX Eclipse XDB-C18(4.6 mm×250 mm,5μm)色谱柱,以甲醇-10 mmol·L-1醋酸铵溶液(用醋酸调节pH至5.7))(1∶9)为流动相,流速1.0 mL·min-1;质谱条件:正离子检测模式,毛细管电压:4.0 kV,锥孔电压:65 V,喷雾气压:310 kPa,干燥气(氮气)流量:11 L·min-1,干燥气温度:350℃,碎裂电压150 V;结吉西他滨与该杂质的多级质谱裂解规律,研究质谱碎片裂解途径,鉴定该杂质的结构。。结果该未知杂质为2'-脱氧-2',2'-二氟尿苷。结论本实验为药物的杂质控制和工艺优化提供参数,进而提高用药安全性。

OBJECTIVE To elucidate the structure of the major impurity in gemcitahine hydrochloride for injection. METHODS HPLC-QTOF-MS was adopted to analyze the structure of this impurity based on the fragmentation behavior of gemcitabine and this impurity. The separation was performed on a ZORBAX Eclipse XDB-C18 （4. 6mm×250mm,5μm） column. A mixture of 10% meth- anol and 90% 10 mmol·L^-1 ammonium acetate（pH 5.7） was used as mobile phase. Flow rate was 1.0 mL · min ^-1. MS was per- formed under positive mode with 4. 0 kV capillary voltage, 65 V skimmer, 310 kPa spray pressure, 11 L · min ^-1 drying gas （nitrogen） flow rate, 350 %2 drying gas temperature and 150 V fragmentor. CONCLUSION This study offers scientific data for studying the ori- gin of the imt）urity of gemcitabine hydrochloride and improving its quality.