呋塞米及其片剂中糠醛的测定和评价

Determination and evaluation of furfural in furosemide and its tablets

目的:建立测定呋塞米及其片剂中遗传毒性杂质糠醛的方法,通过对测定结果进行分析和评估,为国家药品监管提供参考,保障用药安全。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-乙腈为流动相进行梯度洗脱,检测波长为276 nm,对方法进行验证并测定6批呋塞米和148批呋塞米片中的糠醛含量。结果:糠醛的检测限为4 ng·mL^(-1),定量限为12 ng·mL^(-1);在0.0120~0.6023μg·mL^(-1)范围内线性关系良好(r=1.000);原料药及片剂中糠醛的平均回收率分别为99.4%(RSD=0.99%)和101.4%(RSD=1.3%)。所有批次的原料药及片剂样品中均检出糠醛,使用企业I原料药的片剂中糠醛含量明显高于使用企业H原料药的片剂。结论:本方法专属性强,灵敏度高,准确度好,可用于呋塞米及其片剂中杂质糠醛的测定。通过对测定结果进行分析和对糠醛来源及控制策略进行讨论,为实现对呋塞米片的质量控制打下基础。

Objective:To establish a method for determination genotoxic impurity furfural in furosemide and its tablets.To analyze and evaluate the measurement results to provide a reference for national drug supervision and ensure drug safety.Methods:The chromatographic column was filled with octadecylsilane bonded silica gel,and the gradient elution was performed with phosphoric acid solution and acetonitrile as the mobile phase.The detection wavelength was 276 nm.The method was validated and used to determine the furfural content in 6 batches of furosemide and 148 batches of furosemide tablets.Results:The detection limit of furfural was 4 ng·mL^(-1)and the quantitation limit was 12 ng·mL^(-1).The linearity between 0.0120-0.6023μg·mL^(-1)(r=1.000)was good.The average recoveries of furosemide and its tablets were 99.4%(RSD=0.99%)and 101.4%(RSD=1.3%).Furfural was detected in all batches of raw materials and tablet samples.The furfural content in the tablet products,which used the raw materials from company I,was significantly higher than that of the prod⁃ucts obtained from company H.Conclusion:This method has strong specificity,high sensitivity and good accuracy.It can be used for the determination of genotoxic impurity furfural in furosemide and its tablets.By analyzing the measurement results and discussing the sources and control strategies of furfural,quality control of furosemide tablets can be achieved.