注射用头孢他啶杂质研究

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,5 μm),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1000 mL,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 ceftazidime for injection from GlaxoSmithKline and domestic products,and study the major unknown impurities. Methods: The HPLC system was employed which consisted of phenomenex Gemini C₁₈ column(4.6 mm×250 mm,5 μm),mobile phase A ,and mobile phase B (acetonitrile),as gradient elution with UV detection for TOF LC/MS at 254 nm,and the flow rate 1.3 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 impurity profile of the original product was different from that of the domestic ceftazidime,indicating that they may have different synthetic routes. Conclusion: Impurity 24 in domestic products is high which should be controlled by manufacturing technique improvement.

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