目的 研究注射用头孢唑肟钠的杂质谱,进而分析杂质来源,寻找控制杂质的策略。 方法 建立超高效液相色谱法(UPLC)梯度洗脱法测定国内8家企业样品的杂质谱,并利用UPLC-MS联用技术对主要的共有杂质进行结构推定。结果 采用UPLC梯度洗脱方法可检出头孢唑肟异构体、开环物、聚合物等多个杂质,检出的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。
Abstract
OBJECTIVE To investigate the impurity profile of ceftizoxime sodium for injection and develop the impurity control strategy. METHODS Eight batches of ceftizoxime sodium for injection from different manufacturers were tested by UPLC. The major impurities were identified by UPLC-MS. RESULTS The number and amount of impurities detected by UPLC were more than those tested by statutory method. The impurity profile consisted of ceftizoxime isomers, ring-opening products and dimers. CONCULSION The impurities can originate from the process of synthesis of raw material, subpackage of preparation, transportation and storage. It is important to control the key technology indicators and environmental conditions.
关键词
注射用头孢唑肟钠 /
杂质谱 /
液相色谱-质谱联用 /
质量控制
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Key words
ceftizoxime sodium for injection /
impurity profile /
UPLC-MS /
quality control
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中图分类号：
R917
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参考文献
[1] China Pharmacopoeia Committee. Chinese Pharmacopoeia Clinical Medication Notice (2010) Chemical Drugs And Biological Products vol(中华人民共和国药典临床用药须知 2010年版化学药品和生物制品卷) [M]. Beijing: Chinese Medicine Science and Technology Press, 2010: 670-672.[2] Ch.P (2010) Vol II(中国药典2010年版.二部)[S]. 2010: 204.[3] WANG C G, ZHANG Z, WANG J Q, et al. Analysis of related substances in Bromhexine Hydrochloride Tablets [J]. Chin Pharm J (中国药学杂志), 2013, 48(4): 304-308.[4] HU M, HU C Q, LIU W Y. Identification of degradation compounds of cephalosporins by LC-MS[J].Chin J Pharm Anal (药物分析杂志), 2005,25 (3):369-373.[5] OKAMOTO Y, KIRIYAMA K, NAMIKI Y, et al. Degradation kinetics and isomerization of cefdinir, a new oral cephlosporin, in aqueous solution[J].J Pharm Sci, 1996,85(9):976-983.[6] JIANG Y, ZHANG Z F, WANG H. Isomeric impurity research and quality control of β-lactam antibiotics [J].Chin J Antibiot (中国抗生素杂志),2010,35(8):561-566.[7] HU C Q, JIANG Y, ZHANG J B, et al. Reflection on strategy and methods on trace unstable impurities of β-lactam antibiotics [J]. Chin New Drugs J(中国新药杂志),2013,22(1):4-12.
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