双氢青蒿素原料药及其片剂中杂质diketo aldehyde的含量测定

Determination of impurity diketo aldehyde in bulk drug and preparations of dihydroartemisinin

双氢青蒿素与无水溴化亚铁在氮气保护的条件下合成双氢青蒿素中杂质diketo aldehyde (DKA),并建立HPLC测定双氢青蒿素原料药及其片剂中DKA含量的方法。该研究采用双氢青蒿素原料与无水溴化亚铁反应制得DKA,含量测定时采用的色谱柱为Agilent Eclise XDB-C18柱(4. 6 mm×250 mm,5μm),流动相为乙腈-水(37∶63),流速1. 0 mL·min-1,柱温15℃,检测波长216 nm,进样体积40μL。所建立的方法分离度良好,线性关系、稳定性、精密度、重复性、加样回收试验均符合《药品质量标准分析方法验证指导原则》要求。结果显示,13批双氢青蒿素原料药中DKA质量分数为0. 086 7%~2. 622 9%,10批双氢青蒿素片剂中DKA质量分数为0. 068 3%~0. 615 1%。

Diketo aldehyde(DKA),one of the most important impurities in dihydroartemisinin,was synthesized through reaction between dihydroartemisinin and anhydrous ferrous bromide under a N2 atmosphere,and an HPLC method was established for the determination of DKA in bulk drug and in DHA tablet. DKA was prepared from dihydroartemisinin in the presence of Fe Br2. The chromatographic separation was achieved through an Agilent Eclise XDB-C18 column(4. 6 mm × 250 mm,5 μm),and the optimal mobile phase consisted of acetonitrile and water in the ratio of 37∶ 63 at flow rate of 1. 0 mL·min-1. The detection was carried out at 216 nm,and column temperature was 15 ℃. The injection volume was 40 μL. The method featured a good linearity(r = 0. 999 9),precision(1. 0%),repeatability(1. 3%),stability(DKA standards RSD = 1. 0% and in tablet form instability),recovery(92. 88%),limits of detection(0. 20 mg·L-1),and limits of quantification(0. 78 mg·L-1). The result show that the content of DKA in bulk drug was0. 086 7%-2. 622 9%,and the content of DKA in tablet was 0. 068 3%-0. 615 1%.