摘要
目的:对国产注射用头孢他啶与原研厂产品的杂质进行分析,对其中的主要杂质进行初步研究。方法:HPLC法,采用菲罗门Gemini C18柱(4.6 mm×250 mm,5μm),流动相A为磷酸盐缓冲液(磷酸氢二钠3.6 g与磷酸二氢钾1.4 g加水至1000mL,用10%磷酸调pH 3.4),流动相B为乙腈,梯度洗脱,流速:1.3 mL.min-1,柱温:40℃,紫外检测器:检测波长254 nm;TOF质谱检测器。结果:国产样品共检出37个杂质,其中,杂质2、12、24(即BP中的杂质F、A、H)是主要杂质,平均含量分别为0.23%,0.17%,0.48%;来自合成的杂质24为85%,属样品中的最大杂质;杂质总量平均为1.43%。原研产品主要含杂质2、12,含量分别为0.20%和0.18%;最大杂质为杂质2;杂质总量为0.85%。原研产品与国产头孢他啶杂质谱不同;两者可能具有不同合成路线。结论:国产注射用头孢他啶中杂质24含量高,应优化生产工艺,控制其含量。
Objective：To analyze the related substances of ceflazidime for injection from GlaxoSmithKline and do- mestic products, and study the major unknown impurities. Methods：The HPLC system was employed which consis- ted of phenomenex Gemini C 18 column （4.6 mm ×250mm,5μm）, mobile phase A [ phosphate buffer solution （3.6 g disodium hydrogen phosphate and 1.4 g monobasie potassium phosphate in 1000 mL water, pH adjusted to 3.4 with 10% phosphoric acid ）] ,and mobile phase B （acetonitrile）,as gradient elution with UV detection for TOF LC/MS at 254 nm, and the flow rate i. 3 mL · min^-1,the column temperature was administrated at 40℃. Results： There were 37 impurities detected in domestic products. The major impurities were impurity 2,12 and 24 （ impurity F,A,H in BP） with the average contents of 0. 23% ,0. 17% and 0. 48% respectively; the maximum impurity in 85% samples was impurity 24 which came from synthetic process ; the average amount of impurities was 1.43%. The major impurities in GlaxoSmithKline product were impurity 2 and 12, the contents of which were 0.20% and 0. 18% respectively; the maximum impurity was impurity 2 ; the total amount of impurities was 0. 85%. The impuri- ty profile of the original product was different from that of the domestic eeftazidime, indicating that they may have different synthetic routes. Conclusion：Impurity 24 in domestic products is high which should be controlled by man- ufacturing technique improvement.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2012年第12期2234-2239,共6页
Chinese Journal of Pharmaceutical Analysis
基金
十二五国家科技重大专项"重大新药创制"课题"化学新药质量标准研究与评价技术平台"之"化学原料药"子课题
