摘要
目的:对注射用头孢美唑钠中的杂质结构进行分析。方法:采用Phenomenex Gemini C_(18)(250 mm×4. 6 mm,5μm)色谱柱,以磷酸二氢铵溶液-甲醇-四氢呋喃-20%四丁基氢氧化铵(700∶280∶25∶6. 4,v/v,pH=4. 5)为流动相分离杂质;对注射用头孢美唑钠进行强制降解实验,归属杂质来源;采用柱切换-LC/MSn技术采集杂质的质谱数据,根据头孢菌素类抗生素的质谱裂解规律和降解反应机制,推定相关杂质的化学结构。结果:在制剂中共检出并推断了6种杂质的化学结构,包括3种降解杂质和3种工艺杂质,未检出聚合物类杂质。结论:采用柱切换-LC/MSn技术可快速推定注射用头孢美唑钠中相关杂质的化学结构,《中华人民共和国药典》(Ch P) 2015年版的注射用头孢美唑钠有关物质检测方法需要进一步优化和提高。
Objective:To characterize the impurity structures in cefmetazole sodium for injection.Methods:Impurities in cefmetazole sodium for injection were separated on a Phenomenex Gemini C18 column(250 mm×4.6 mm,5μm),with ammonium dihydrogen phosphate-methanol-tetrahydrofuran-20%butyl ammonium hydroxide(700∶280∶25∶6.4,v/v,pH 4.5)as mobile phase(pH 4.5).Stress tests were designed and performed on the cefmetazole sodium for injection to specify the impurities.By application of on-line column-switching LC/MSn method,the impurities were collected and their structures were characterized based on the mass fragmentation regularity and degradation mechanism of cephalosporin antibiotics.Results:A total of six impurities were detected and characterized in the product including three degradation products and three impurities derived from synthesis process,but no polymer impurities were detected.Conclusion:The structures of related impurities in cefmetazole sodium for injection can be rapidly identified by on-line column-switching LC/MSn method,and the related substance specification of cefmetazole sodium for injection in China Pharmacopeia(ChP)2015 edition should be further optimized and improved.
作者
李进
姚尚辰
胡昌勤
LI Jin;YAO Shang-chen;HU Chang-qin(National Institutes for Food and Drug Control,Beijing 102629,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2019年第8期984-995,共12页
Chinese Journal of New Drugs
关键词
头孢美唑钠
杂质
杂质谱
柱切换
液相/质谱
头孢菌素
抗生素
cefmetazole sodium
impurity
impurity profile
column switching
LC/MSn
cephalosporin
antibiotics
