埃索美拉唑镁盐多晶型的X-射线粉末衍射定量分析

目的:用X-射线粉末衍射法测定埃索美拉唑镁三水合物和二水合物A晶型混合物中晶型的含量,为埃索美拉唑镁晶型药物的质量控制提供一种切实可行的晶型定量分析方法。方法:采用X-射线粉末衍射法表征埃索美拉唑镁盐三水合物晶型和二水合物A晶型。分别选择埃索美拉唑镁三水合物的特征衍射峰2θ=5.27°(I/I₀=100%)和二水合物A晶型的特征衍射峰2θ=5.65°(I/I₀=100%)的峰面积比值为定量参数,建立标准曲线,测定埃索美拉唑镁原料中三水合物晶型和二水合物A晶型的含量。结果:埃索美拉唑镁二水合物A晶型的特征衍射峰和三水合物的特征衍射峰的峰面积比值与三水合物的含量呈良好的线性关系,在三水合物含量为3%~15%的范围内,得到的标准曲线为Y=0.0043X+0.3136;Y为特征衍射峰的峰面积比,X为三水合物的质量分数,相关系数r=0.9996;方法精密度为2.4%;运用标准曲线对三水合物含量为5.48%、10.33%、12.49%的样品进行定量分析,结果表明测得值与真实值之间的绝对误差分别为0.14%、0.01%、0.06%。结论:所建方法准确可靠,快速简便,可用于埃索美拉唑镁原料中三水合物晶型和二水合物A晶型的定量分析。

Objective:To devise a method for the quantification of the polymorphic purity of esomeprazole magnesium in mixtures formed by polymorphs trihydrate and dihydrate form A using X-ray power diffraction technique. Methods:In the present study, X-ray power diffraction technique was used for setting up quantitative standard curve. A calibration curve was constructed in the range of 0%-100% (w/w) or 3%-15% (w/w) using the characteristic peak ratio of esomeprazole magnesium trihydrate at 5.27° 2θ (I/I₀=100%) and esomeprazole magnesium dihydrate form A at 5.65° 2θ (I/I₀=100%) as the quantitative parameters to determine the contents of the polymorphs. Results:The quantification method developed was found to be in good linearity in the range of 3%-15% (w/w), and the obtained standard curve was Y=0.004 3X+0.313 6, Y expressing the ratio of characteristic peaks, X indicating the mass fraction of esomeprazole magnesium trihydrate. The correlation coefficient was 0.999 6 and the precision was 2.41%. The standard curve was used to quantify several samples with contents being 5.48%, 10.33%, and 12.49% respectively and validation results showed the errors between actual and calculated concentrations were 0.14%, 0.01%, and 0.06% respectively. Conclusion:X-ray powder diffraction method is a feasible analytical method for quantitative determination of trihydrate and dihydrate form A for esomeprazole magnesium, and it is simple, sensitive and accurate.