HPLC法与滴定法测定磷酸伯氨喹原料药含量的比较

Comparative Study on the Content Determination of Primaquine Phosphate by HPLC and Titration

目的：为第五版《国际药典》磷酸伯氨喹原料药的标准修订提供依据。方法：参照各国磷酸伯氨喹及其制剂的检验标准,采用高效液相色谱法（HPLC）与高氯酸电位滴定法、亚硝酸钠永停滴定法测定磷酸伯氨喹原料药的含量并进行比较。结果：采用HPLC法,磷酸伯氨喹的检测质量浓度线性范围为128.1～384.2μg/ml（r=0.999 9）;检测限为0.18μg/ml,定量限为0.59μg/ml;精密度、稳定性、重复性试验的RSD〈1%;回收率为99.42%～101.14%（RSD=0.6,n=9）;破坏性试验和耐用性试验的专属性均较好;3批样品的含量分别为92.1%、92.3%、92.0%。采用高氯酸电位滴定法,精密度、重复性试验的RSD均为1.6%;该方法滴定终点突跃不明显;3批样品的含量分别为99.1%、99.7%、98.7%。采用亚硝酸钠永停滴定法,精密度、重复性试验的RSD〈1%;该方法滴定终点突跃明显;3批样品的含量分别为96.9%、97.1%、96.7%。采用亚硝酸钠外指示剂法相比亚硝酸钠永停滴定法的精密度更好;3批样品的含量分别为99.6%、100.0%、99.5%。结论：高氯酸电位滴定法操作简便、快速,但精密度、重复性相对较差,检测结果包含杂质喹西特含量。亚硝酸钠永停滴定法操作简便,精密度和重复性较好,但反应时间长,检测结果也包含杂质喹西特含量。而HPLC法分离效果好、准确性高,能有效分离磷酸伯氨喹原料药中的主要杂质喹西特,适用于其质量控制。

OBJECTIVE：To provide reference for revising the standards of primaquine phosphate in International Pharmacopoeia（the fifth edition）. METHODS：Based on inspection standards for primaquine phosphate and its preparations in different countries,HPLC,perchloric acid potentiometric titration and sodium nitrite dead-stop titration were adopted to determine and compare the contents of primaquine phosphate. RESULTS：In HPLC,the linear range of primaquine phosphate was 128.1-384.2 μg/ml（r=0.999 9）;the limit of detection was 0.18 μg/ml,the limit of quantification was 0.59 μg/ml;RSDs of precision,stability and reproducibility tests were lower than 1%;recovery was 99.42%-101.14%（RSD=0.6,n=9）;destructive test and durability test showed good specificity;the contents of 3 batches of samples were 92.1%,92.3% and 92.0%,respectively. In perchloric acid potentiometric titration,RSDs of precision and reproducibility tests were 1.6%;the titration jump was not obvious;the contents were 99.1%,99.7% and 98.7%,respectively. In sodium nitrite dead-stop titration,RSDs of precision and reproducibility tests were lower than1%;the titration jump was obvious;the contents were 96.9%,97.1% and 96.7%,respectively. Sodium nitrite external indicator titration showed better precision than dead-stop titration;the contents were 99.6%,100.0% and 99.5%,respectively. CONCLUSIONS：Perchloric acid potertiometric titration is simple and rapid,but with relatively poor precision and reproducibility,and it contains quinocide. Sodium nitrite dead-stop titration is simple with good precision and reproducibility but long reaction time,and it also contains quinocide,the HPLC method shows good separation and high accuracy,can effectively separate the quinocide in primaquine phosphate,and it is suitable for the quality control of primaquine phosphate.