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pH 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(pH 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。
Abstract
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 polymer 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-1 phosphate buffer (pH 7.0) as the mobile phase. An XBridge C18 column was used in the second dimensional chromatography, with gradient elution using 10 mmol·L-1ammonium formate solution(pH 6.5) and 8 mmol·L-1ammonium formate in mixture of acetonitrile and water (200∶50) as the mobile phase. Two mass spectrometers with ESI source were used for 2D-LC-MSn.RESULTS The polymer impurities 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
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Key words
azlocillin sodium for injection /
polymer impurity /
2D-LC /
MS
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中图分类号：
R917
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参考文献
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脚注
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基金
2015年浙江省公益技术研究社会发展项目资助(2015C33168)
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