利用31P NMR谱快速测定依替膦酸二钠片中依替膦酸钠及其杂质的含量

Rapid determination of etidronate disodium and its impurities in etidronate disodium tablets by 31P NMR spectroscopy

目的:建立核磁共振磷谱分析方法同时测定依替膦酸二钠片中依替膦酸钠及其杂质亚磷酸根、磷酸根的含量。方法:以重水为溶剂,草铵膦为内标,采用5 mmBBO探头测定,温度为296.5 K,扫描64次,对3批依替膦酸二钠片样品进行测定,并与非水电位滴定法测定结果进行比较。结果:依替膦酸钠、亚磷酸根、磷酸根摩尔浓度分别在1.25~400.00、1.25~400.00、1.00~400.00 mmol·L^-1的范围内呈良好的线性关系(R2=1.000),检测下限分别为1.25、1.25、1.00 mmol·L^-1,精密度RSD为0.10%~0.43%(n=6),片剂的平均回收率为99.2%~101.8%,RSD为0.028%~0.42%(n=5),3批样品主成分含量分别为95.65%、97.53%、96.47%。结论:实验结果表明,该方法可为依替膦酸二钠片质量控制提供新的分析依据。

Objective:To establish a31 P NMR method for the simultaneous determination of etidronate disodium and its inpurities in etidronate disodium tablets,including etidronate disodium,phosphite and phosphate.Methods:Glyphosate was used as an internal standard,D2 O was used as a solvent,and three batches of etidronate disodium tablets were determined by 5 mmBBO probe at 296.5 K and 64 times of scanning.The results were compared to those obtained with non-aqueous potentiometric titration.Results:Good linearity(R2=1.000)was achieved for etidronate disodium,phosphite and phosphate in the range of 1.25-400.00,1.25-400.00 and 1.00-400.00 mmol·L^-1.The limits of detection were 1.25,1.25,1.00 mmol·L^-1 for etidronate disodium,phosphite and phosphate,respectively.The RSD of precision was 0.10%~0.43%(n=6),and the average recoveies were 99.2%-101.8%with RSD of 0.028%-0.42%(n=5).The contents of main component in three batches of samples were 95.65%,97.53%and 96.47%,respectively.Conclusion:This method provided a new reliable analytical method for the quality control of etidronate disodium tablets.