叶酸粒度分布的激光衍射测定法研究

Determination of the Particle Size Distribution of Folic Acid Using Laser Diffraction Method

目的建立一种激光衍射法用于测定叶酸粒度分布。方法采用Malvern MS3000激光衍射法粒度分析仪和HYDRO EV湿法进样器,研究并优化重要的光学参数和样品分散条件(分散剂的选择、样品浓度、遮光度、搅拌速度、背景和样品测量时间、样品分散时间、超声方式),并对最终建立的方法进行验证。结果参数设置确定为叶酸折射率1.76;叶酸吸收率0.1;分散介质水;水的折射率1.33;分析模式,通用模式;灵敏度普通;搅拌速度3000 r·min^(-1);测量次数6;背景测量时间10 s;分散时间30 s;样品测量时间10 s;遮光度5%~7%。方法验证的d(0.1)和d(0.9)结果RSD≤15%(n=6),d(0.5)结果RSD≤10%(n=6),均符合USP〈429〉规范。结论该法准确度、重现性和精密度良好,适用于各厂家叶酸原料药粒径的测定。

OBJECTIVE A laser diffraction method was established to measure the particle size distribution of folic acid.METHODS The Malvern MS3000 laser diffraction particle size analyzer and HYDRO EV wet sampler was used.In the meantime,a method was developed and validated by investigating important optical parameters and sample dispersing conditions which included selection of dispersant,sample concentration,obscuration,stirrer speed,sample and background measurement duration,pre-measurement delay and sonication mode.RESULTS The method was as follows:folic acid refractive index:1.76;folic acid absorption index:0.1;dispersion medium:water;refractive index of water:1.33;analysis mode:general mode;common sensitivity;stirrer speed:3000 r·min^(-1);measurement times:6;sample and background measurement duration:10 s;pre-measurement delay:30 s;obscuration limit:5%~7%.The RSD of d(0.1)and d(0.9)measured via methodology validation was≤15%(n=6),and the RSD of d(0.5)was≤10%(n=6),which was in accordance with US P<429>.CONCLUSION The method is precise and reproducible,which is suitable for the determination of particle size of folic acid from various manufacturers.