呋塞米及其制剂中微量基因毒杂质的检测

Determination of trace genotoxic impurities in furosemide and its preparations

目的:建立HPLC法测定呋塞米及其制剂中微量基因毒杂质糠醛的检测方法,提高了呋塞米的质量控制要求。方法:采用十八烷基硅烷键合硅胶为填充剂的色谱柱,以磷酸溶液和乙腈为流动相,检测波长270 nm。结果:呋塞米及其制剂各国药典标准中报道的已知杂质对其检测均不干扰;杂质的检测下限为12 ng·mL^(-1);在0.04~4.088μg·mL^(-1)范围内线性关系良好,r^(2)=1.000;呋塞米及其制剂中的平均回收率分别为99.8%(RSD=2.8%)、98.9%(RSD=0.9%)及100.9%(RSD=2.4%);呋塞米原料及其市售制剂中有0.003%~0.004%的糠醛检出。结论:本方法专属性强、灵敏度高、准确性好,可用于呋塞米及其制剂中潜在基因毒杂质糠醛的有效检测,保证呋塞米制剂的有效性和安全性。

Objective:To establish an HPLC method for determining trace genotoxic impurities in furosemide and its preparations.Methods:The chromatographic column was filled with octadecylsilane bonded silica gel,with phosphoric acid solution and acetonitrile as mobile phase,and the detection wavelength was 270 nm. Results:The known impurities in the pharmacopoeia did not interfere with the detection. The detection limit of impurities was 12 ng·mL^(-1). The linearity between 0.04-4.088 μg·mL^(-1) was good,r^(2)=1.000. The average recoveries of furosemide and its preparations were 99.8%(RSD=2.8%),98.9%(RSD=0.9%)and 100.9%(RSD=2.4%). There were 0.003%-0.004% furfural detected in furosemide and its commercial preparations. Conclusion:This method has high specificity,sensitivity and good accuracy,and can be used to detect furfural,a trace gene toxin impurity in furosemide and its preparations. This method ensures the efficacy and safety of furosemide preparations.