粉末X射线衍射技术定量分析左炔诺孕酮晶型
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摘要
目的针对紧急避孕药左炔诺孕酮的临床药用晶型物质——晶γ型,采用粉末X射线衍射法建立其原料药中晶γ型定量分析方法。方法采用单晶X射线衍射法和粉末X射线衍射法确定了制备的左炔诺孕酮晶γ型为100%晶型纯品,为单峰法定量分析提供标准样品。称取不同质量左炔诺孕酮晶γ型的标准样品进行粉末X射线衍射实验,选择晶γ型的特征衍射峰d=6.4、d=6.1和d=5.6的峰强度值为定量参数,建立峰强度值与晶型质量间的线性关系,用于定量分析左炔诺孕酮原料药中晶γ型的含量。结果左炔诺孕酮晶γ型中3个(d=6.4、d=6.1和d=5.6)特征衍射峰的峰强度值与晶γ型的质量呈良好的线性关系;在晶γ型质量为5～50 mg内,回归线性方程分别为Y=459.59X+5 536.5,R2=0.993 0、Y=430.03 X+6 867.6,R2=0.990 5和Y=615.95 X+6 209.5,R2=0.990 8。结论该方法操作简单便捷,定量分析准确可靠,可作为左炔诺孕酮原料药的晶型质量控制方法。
Objective According to the clinical medicinal crystal form——form γ of levonorgestrel,to establish the quantitative analysis method for levonorgestrel form γ by powder X-ray diffraction( PXRD). Methods Firstly,single crystal X-ray diffractometry and powder X-ray diffractometry were used to confirm that the prepared levonorgestrel form γ was 100%polymorphic purity,which provided a standard sample for quantitative analysis by single peak method; then,the standard samples of different quality levonorgestrel form γ for powder X-ray diffraction were weighed,the peak intensity values of characteristic diffraction peaks d = 6.4 ,d = 6. 1 and d = 5. 6 of form γ as quantitative parameters selected,a linear relationship between the peak intensity value and the quality of form γ was established; finally,the content of levonorgestrel formγ was quantitatively analyzed. Results The peak intensity values of characteristic diffraction peaks d= 6.4 ,d= 6.1 and d = 5.6 of levonorgestrel form γ and the quality showed a good linear relationship.In the range of form γ masses of 5 mg to 50 mg,the regression linear equations were Y = 459.59X+5 536.5,R2= 0.993 0,Y = 430.03X+6 867.6,R2= 0.990 5,Y = 615.95X+6 209.5,R2= 0.990 8,respectively. Conclusion The method is simple,rapid,accurate and reliable,it can be used as quality control method for levonorgestrel polymorphs.
Objective According to the clinical medicinal crystal form——form γ of levonorgestrel,to establish the quantitative analysis method for levonorgestrel form γ by powder X-ray diffraction( PXRD). Methods Firstly,single crystal X-ray diffractometry and powder X-ray diffractometry were used to confirm that the prepared levonorgestrel form γ was 100%polymorphic purity,which provided a standard sample for quantitative analysis by single peak method; then,the standard samples of different quality levonorgestrel form γ for powder X-ray diffraction were weighed,the peak intensity values of characteristic diffraction peaks d = 6.4 ,d = 6. 1 and d = 5. 6 of form γ as quantitative parameters selected,a linear relationship between the peak intensity value and the quality of form γ was established; finally,the content of levonorgestrel formγ was quantitatively analyzed. Results The peak intensity values of characteristic diffraction peaks d= 6.4 ,d= 6.1 and d = 5.6 of levonorgestrel form γ and the quality showed a good linear relationship.In the range of form γ masses of 5 mg to 50 mg,the regression linear equations were Y = 459.59X+5 536.5,R2= 0.993 0,Y = 430.03X+6 867.6,R2= 0.990 5,Y = 615.95X+6 209.5,R2= 0.990 8,respectively. Conclusion The method is simple,rapid,accurate and reliable,it can be used as quality control method for levonorgestrel polymorphs.
引文
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[2]戴黎华,万玉萍,谢春伟,等.左炔诺孕酮宫内缓释系统对乳腺癌患者子宫内膜的保护作用[J].医药导报,2015,34(1):71-73.
[3]陈萍,王芬娟,龚巧丽,等.左炔诺孕酮宫内缓释系统用于卵巢子宫内膜异位囊肿手术后巩固治疗30例[J].医药导报,2012,31(6):708-710.
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[7] ZADBUKE S A,MEHARE K G,GODBOLE H M,et al.Process for preparation of levonorgestrel:2013324748[P].2013-12-05.
[8]徐娟,宁丽峰,李鹏,等.左炔诺孕酮的多晶型研究[J].中国计划生育学杂志,2017,25(1):12-20.
[9]曹俊姿,杨德智,张丽,等.左炔诺孕酮优势药用晶型研究[J].医药导报,2017,36(12):1339-1343.
[10]吕扬,杜冠华.晶型药物[M].北京:人民卫生出版社,2009.
[11]吕扬,张丽,杨世颖,等.多晶型药品的质量控制技术与方法应用要求[J].中国新药杂志,2014,23(7):759-763.
[12] US FDA.Guidance for Industry,ANDAs:Pharmaceutical Solid Polymorphism[S].2007.
[13]徐婷,王彦,朱美兰,等.盐酸文拉法辛多晶型X-射线粉末衍射定量分析[J].中国新药杂志,2017,26(21):2614-2619.
[14]杨世颖,张丽,杜冠华,等.差示扫描量热法对尼群地平晶型的定量分析研究[J].中国新药杂志,2015,24(12):1423-1434.
[15]马乐伟,杜葳,赵春顺.药物晶型定量分析方法的研究进展[J].药学学报,2011,46(8):896-903.
[16]梅梅,李煜,杨伟峰.X-射线粉末衍射技术在多晶型药物定量分析中的应用[J].中国现代应用药学,2017,34(9):1356-1360.
[2]戴黎华,万玉萍,谢春伟,等.左炔诺孕酮宫内缓释系统对乳腺癌患者子宫内膜的保护作用[J].医药导报,2015,34(1):71-73.
[3]陈萍,王芬娟,龚巧丽,等.左炔诺孕酮宫内缓释系统用于卵巢子宫内膜异位囊肿手术后巩固治疗30例[J].医药导报,2012,31(6):708-710.
[4]国家药典委员会.中华人民共和国药典(四部)[M].北京:中国医药科技出版社,2015:338-340.
[5] ASKA Pharm Co Ltd.Crystalline polymorphα,and a method of manufacturing the same levonorgestrel:2014175303[P].2014-04-23.
[6] ASKA Pharm Co Ltd.Crystalline polymorphβ,and a method of manufacturing the same levonorgestrel:2014175304[P].2014-04-23.
[7] ZADBUKE S A,MEHARE K G,GODBOLE H M,et al.Process for preparation of levonorgestrel:2013324748[P].2013-12-05.
[8]徐娟,宁丽峰,李鹏,等.左炔诺孕酮的多晶型研究[J].中国计划生育学杂志,2017,25(1):12-20.
[9]曹俊姿,杨德智,张丽,等.左炔诺孕酮优势药用晶型研究[J].医药导报,2017,36(12):1339-1343.
[10]吕扬,杜冠华.晶型药物[M].北京:人民卫生出版社,2009.
[11]吕扬,张丽,杨世颖,等.多晶型药品的质量控制技术与方法应用要求[J].中国新药杂志,2014,23(7):759-763.
[12] US FDA.Guidance for Industry,ANDAs:Pharmaceutical Solid Polymorphism[S].2007.
[13]徐婷,王彦,朱美兰,等.盐酸文拉法辛多晶型X-射线粉末衍射定量分析[J].中国新药杂志,2017,26(21):2614-2619.
[14]杨世颖,张丽,杜冠华,等.差示扫描量热法对尼群地平晶型的定量分析研究[J].中国新药杂志,2015,24(12):1423-1434.
[15]马乐伟,杜葳,赵春顺.药物晶型定量分析方法的研究进展[J].药学学报,2011,46(8):896-903.
[16]梅梅,李煜,杨伟峰.X-射线粉末衍射技术在多晶型药物定量分析中的应用[J].中国现代应用药学,2017,34(9):1356-1360.