二维高效凝胶色谱反相液相色谱-质谱联用技术分析注射用阿洛西林钠中的聚合物杂质  

2D-HPGFC-RPLC-MS Method for Characterization of Polymer Impurities in Azlocillin Sodium for Injection

作　　者：阮昊 王勇跃 罗英 陈悦 洪利娅 RUAN Hao WANG Yong-yue LUO Ying CHEN Yue HONG Li-ya(Zhejiang Institute for Food and Drug Control, Hangzhou 310052, China Zhefiang University of Technology, Hangzhou 310004, China)

机构地区：[1]浙江省食品药品检验研究院,杭州310052 [2]浙江工业大学,杭州310004

出　　处：《中国药学杂志》2017年第14期1273-1279,共7页Chinese Pharmaceutical Journal

基　　金：2015年浙江省公益技术研究社会发展项目资助(2015C33168)

摘　　要：目的对注射用阿洛西林钠中的聚合物杂质进行分离定位及结构鉴定,并对高效凝胶色谱法测定其聚合物杂质的有效性进行考察。方法利用二维液相色谱-质谱联用技术对注射用阿洛西林钠中的聚合物杂质进行分离定位及结构鉴定。一维高效凝胶色谱以Ultimate SEC-120为色谱柱,以p H 7.0的5 mmol·L^(-1)磷酸盐缓冲液等度洗脱;二维以XBridge C18为色谱柱,以10 mmol·L^(-1)甲酸铵溶液(p H 6.5)和8 mmol·L^(-1)甲酸铵的乙腈-水(200∶50)溶液梯度洗脱。以质谱仪作为检测器对其进行检测,并进行结构鉴定。结果高效凝胶色谱法测定注射用阿洛西林钠的聚合物杂质色谱峰除聚合物杂质外,还包括阿洛西林青霉烯酸及阿洛西林青霉烯酸脱羧产物。反相液相色谱系统中定位出4种聚合物杂质,并推断出其可能的化学结构。结论二维液相色谱-质谱联用技术可有效分离、定位并鉴定注射用阿洛西林钠中的聚合物杂质,为有效控制β-内酰胺抗生素中的聚合物杂质提供了新思路。OBJECTIVE To establish a method for the separation and characterization of polymer impurities in azlocillin sodium for injection, and evaluate the efficacy of high performance gel filtration chromatography （HPGFC） method for determination of the pol- ymer impurities. METHODS Using two-dimensional HPGFC and reversed-phase liquid chromatography （RPLC）-mass spectrometer, an Ultimate SEC-120 column was used in the first dimensional chromatography, with isocratic elution using 5 mmol · L-l phosphate buffer （pH 7.0） as the mobile phase. An XBridge C18 column was used in the second dimensional chromatography, with gradient elu- tion using 10 mmol ·L - l ammonium formate solution （ pH 6. 5 ） and 8 mmol ·L - 1 ammonium formate in mixture of acetonitrile and wa- ter （200： 50） as the mobile phase. Two mass spectrometers with ESI source were used for 2D-LC-MSn. RESULTS The polymer im- purities found by HPGFC also included penicillenic acid of azlocillin and decarboxylated penicillenic acid of azlocillin. The chemical structures of four polymer impurities identified in the second dimensional RPLC were elucidated. CONCLUSION The 2D-HPGFC- RPLC-MS method can be used to profile the polymer impurities in azlocillin sodium for injection, which is helpful to realize effective control over polymer impurities in β-lactam antibiotics.

关 键 词：注射用阿洛西林钠 聚合物杂质 二维液相色谱 质谱 

分 类 号：R917[医药卫生—药物分析学]