改进双氢青蒿素哌喹片中双氢青蒿素的溶出度测定方法

Improvement of Determination Method for the Dissolution of Dihydroartemisinin in Dihydroartemisinin and Piperaquine Phosphate Tablets

目的:改进双氢青蒿素哌喹片中双氢青蒿素的溶出度测定方法。方法:采用桨法进行溶出试验,以0.1 mol/L盐酸溶液为溶出介质,溶出介质体积为500 mL,转速为75 r/min,取样时间为45 min;样品前处理中加入3.6%氢氧化钠溶液的体积由原来的5mL改为20 mL,加入磷酸的体积由原来的0.2 mL改为0.7 mL。采用高效液相色谱法测定制剂中双氢青蒿素的溶出度:色谱柱为YMC-Pack ODS-A,流动相为0.02 mol/L磷酸氢二钠溶液(用磷酸调节p H为2.4)-乙腈(65∶35,V/V),流速为1.0 mL/min,检测波长为237 nm,柱温为30℃,进样量为20μL。结果:双氢青蒿素检测质量浓度线性范围为7.802~117.03μg/mL(r=0.999 9);定量限为2.0 ng,检测限为0.6 ng;精密度、重复性试验的RSD<1.0%;回收率为99.18%~100.46%(RSD=0.45%,n=9)。3批样品中双氢青蒿素的平均溶出度分别为94.9%、77.9%、89.6%。结论:改进后的方法提高了其灵敏度、溶出度以及检测结果的准确性。

OBJECTIVE： To improve the detection method for the dissolution of dihydroartemisinin in Dihydroartemisinin and piperaquine phosphate tablets. METHODS： The dissolution experiment adopted paddle method using 0.1 moFL hydrochloric acid so- lution 500 mL as solvent with rotating speed of 75 r/min and sampling time of 45 rain. In sample pre-treatment, the volume of 3.6% sodium hydroxide solution was increased from 5 mL to 20 mL, and that of phosphoric acid was increased from 0.2 mL to 0.7 mL. HPLC was adopted to determine the dissolution of dihydroartemisinin. The determination was performed on YMC-Pack ODS-A column with mobile phase consisted of 0.02 mol/L disodium hydrogen phosphate solution（pH adjusted to 2.4 using phosphoric ac- id）-acetonitrile （65：35, V/V） at the flow rate of 1.0 mL/min. The detection wavelength was set at 237 nm, and column temperature was 30 ℃. The sample size was 20 gL. RESULTS： The linear range of dihydroartemisinin were 7.802-117.03 μg/mL （r=0.999 9）. The limit of quantitation was 2.0 ng, and the limit of detection was 0.6 rig, RSDs of precision and reproducibility tests were all low- er than 1.0%. The recoveries were 99.18%-100.46% （RSD=0.45% ,n=9）. Average dissolutions of dihydroartemisinin in 3 batch- es of samples were 94.9%, 77.9%, 89.6%, respectively. CONCLUSIONS： Improved method enhance the accuracy for the limit of sensitivity, dissolution and detection results.