HPLC法测定盐酸头孢他美酯中的有关物质和聚合物

目的: 建立HPLC梯度洗脱法同时测定盐酸头孢他美酯中的有关物质和聚合物。方法: 采用Thermo Acclaim^TM 120 C₁₈ 色谱柱(250 mm×4.6 mm,5 μm),流动相A为乙腈-甲醇-水-磷酸盐缓冲液(180:47.5:750:67.5),流动相B为乙腈-甲醇-水-磷酸盐缓冲液(540:142.5:250:22.5),梯度洗脱(0 min,0%B;2 min,0%B;30 min,100%B;45 min,100%B;46 min,0%B;55 min,0%B),流速为1.0 mL · min^-1,检测波长为233 nm。结果: 盐酸头孢他美酯与中间体、分解产物完全分离。杂质头孢他美酸、AE活性酯和7-氨基-3-去乙酰氧基头孢烷酸(7-ADCA)的回收率分别为97.8%、98.3%和104.4%,重复性RSD为2.8%,定量限为0.04~0.21 μg · mL^-1。各有关物质测定结果,头孢他美酸为1.0%~1.6%,异构体1为0.2%~0.9%、异构体2为0.1%~0.2%、二聚物1为0.1%~0.3%、二聚物2为0.2%~0.8%。结论: 建立的方法经方法学验证可用于本品的质量控制。

Objective: To develop an HPLC-gradient elution method for simultaneous determination of related substances and polymers in cefetamet pivoxil hydrochloride. Methods: The column was Thermo Acclaim^TM 120 C₁₈ ⁽250 mm×4.6 mm, 5 μm). The mobile phase consisted of acetonitrile-methanol-water- phosphate buffer (180: 47.5: 750: 67.5) (A) and acetonitrile-methanol-water-phosphate buffer (540: 142.5: 250: 22.5) (B) with gradient elution program (0 min, 0%B;2 min, 0%B;30 min, 100%B;45 min, 100%B;46 min, 0%B;55 min, 0%B). The flow rate was 1.0 mL · min^-1, and the detection wavelength was 233 nm. Results: Good separation of cefetamet pivoxil from intermediates and degradation products was achieved. The recoveries of impurities cefetamet acid, AE active ester and 7-aminodesacetoxycephalosporanic acid (7-ADCA) were 97.8%, 98.3% and 104.4%.The RSD of repeatability was 2.8%.The quantitation limit was 0.04-0.21 μg · mL^-1.The contents of cefetamet acid, isomer 1, isomer 2, dimer 1 and dimer 2 were 1.0%-1.6%, 0.2%-0.9%, 0.1%-0.2%, 0.1%-0.3% and 0.2%-0.8%. Conclusion: The method meets the requirement of methodology validation, and can be used for quality control of cefetamet pivoxil hydrochloride.

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