激光散射法测定双氢青蒿素原料药的粒度

Particle Size Determination for Dihydroartemisinin APIs by Laser Light Scattering Method

目的:建立激光散射法测定双氢青蒿素原料药的粒度大小和分布。方法:样品采用吐温80水溶液分散后强力振摇2 min,再超声90 s制成样品混悬液。然后采用Malvern Mastersizer 3000型激光粒度分析仪进行测试,进样模式为湿法,样品折射率1.520,样品吸收率0.1,分散剂折射率1.330,遮光度10%~25%,搅拌速度1 500 r·min-1,样品测量3次,样品测量时间和背景测量时间均为10.0 s。结果:方法验证结果:重复性RSD(n=6):d(0.5)为6.4%,d(0.1)为9.5%,d(0.9)为9.8%;中间精密度RSD(n=12):d(0.5)为8.0%,d(0.1)为15.3%,d(0.9)为11.6%;耐用性:不同搅拌速度(±10%)和测量时间(±2 s)得到的结果,d(0.5)的RSD均小于4%,d(0.1)的RSD均小于3%,d(0.9)的RSD均小于7%;溶液稳定性:样品混悬液和样品池混悬液在室温下放置1 h内得到的结果,d(0.5)的RSD均小于3%,d(0.1)的RSD均小于4%,d(0.9)的RSD均小于4%,方法验证结果均符合USP<429>的规定。3批样品的测定结果中,d(0.5)的RSD均小于3%,d(0.1)和d(0.9)的RSD均小于5%,结果准确。结论:本方法操作简便、结果准确、精密度好,可用于有效控制双氢青蒿素原料药的粒度。

Objective:To establish a laser light scattering method for the determination of particle size and distribution of dihydroartemisinin APIs.Methods:Samples were prepared to be a suspension with Tween 80 aqueous solution as the dispersant,by vigorously shaking it for 2 min and then ultrasonic processing it for90 s.A Malvem MasterSizer 3000 type laser size analyzer was used with a wet auto-sampler.Sample refractive index was 1.520,absorbency was 0.1,dispersant refractive index was 1.330,shading degree was 10%-25%,stirring speed was 1500 r·min-1,sample measuring counts was 3,measuring time for background and samples were both 10.0 s.Results:Method validation results:The RSD(n=6)of repeatability for d(0.5)was 6.4%,for d(0.1)was 9.5%and for d(0.9)was 9.8%.The RSD(n=12)of intermediateprecision for d(0.5)was 8.0%,for d(0.1)was 15.3%and for d(0.9)was 11.6%.Robustness:Under the condition of different stirring speed(±10%)and different measuring time(±2 s),the RSD for d(0.5)were all lower than 4%,for d(0.1)were all lower than 3%and for d(0.9)were all lower than 7%.Solution stability:Within 1 h of sample suspension and sample cell suspension were placed at ambient temperature for,the RSD for d(0.5)were all lower than 3%,for d(0.1)were all lower than 4%and for d(0.9)were all lower than 4%.All the method validation results complied with the requirements of USP<429>.The RSD of measuring results of 3 batches of samples for d(0.5)were all lower than 3%,for d(0.1)and d(0.9)were all lower than 5%,which demonstrated the results was accurate.Conclusion:The established method is simple in operation,accurate and precise,which is applicable for effective control of particle size and distribution of dihydroartemisinin APIs.