【作者】 胡岩；

【导师】 王永生；

【作者基本信息】 长春中医药大学 ， 中药学， 2011， 硕士

【摘要】 目的:本文对原料药1-甲基海因进行了较为完善的质量研究,着重对1-甲基海因的有关物质和含量测定方法及其限度以及稳定性考察进行了系统的研究。方法:本文对1-甲基海因质量控制方法建立了其鉴别、杂质检查、有关物质及含量测定等项目的测定方法,首次用高效液相色谱仪DAD检测器确定了有关物质的测定方法,选择用agela venusil MP C18柱,(5um,250mm×4.6mm),流动相为0.2%磷酸水溶液;检测波长:200nm;在鉴定有关物质2-(1-甲基脲基)乙酸结构中,采用了元素分析、EI-MS、1H-NMR、1C-NMR、IR等现代光谱技术综合分析,最终确定为2-(1-甲基脲基)乙酸。结果:所建立的有关物质检查方法具有良好的专属性,1-甲基海因的浓度在0.10～0.60ug范围内,峰面积与其浓度呈良好线性关系(r=0.9997),检测限为2ng(S/N=3),精密度试验RSD=0.12%,重复性试验RSD为0.67%。本文还建立了用非水溶液中和法测定1-甲基海因含量的方法。同时为1-甲基海因原料药初步制订了药品质量标准,并进行了1-甲基海因稳定性的影响因素试验和加速试验,结果表明1-甲基海因对光、湿、热稳定。结论:本文为制订1-甲基海因原料药质量标准以及贮藏条件和有效期提供了依据,同时为制剂的研发和生产工艺标准的设计提供了参考,不仅填补了国内外在1-甲基海因质量控制研究领域的空白,并且为1-甲基海因开发成为国家一类新药及其更广阔的应用奠定了基础。更多还原

【Abstract】 Purpose: This article on raw materials of l-Methylhydantoin for better quality,focus on the relative substance of l-Methylhydantoin and determination method and its limits and stability research on the system.Method:In this thesis, the quality control in-depth study about l-Methylhydantoin is established for chemical identification,checking impurities, the relative substance and substance determination etc.For the first time,HPLC-DAD detector is used to identify and determine the relative substance, with the usage of agela venusil MP C18 column(5um,250mm×4.6mm), the mobile phase was 0.2% phosphate solution, 200nm as detective wavelength. In the identification of the relative substance of 2– (1 - methyl - urea - based) acetic acid structure, use element analysis, EI-MS, 1H-NMR, 1C-NMR, IR and so on analysis of modern spectrum technologies and final set at 2– (1 - methyl - urea - based) acetic acid.Result:The established method has a good specification,linearity and precision within the range of 0.10- 0.60ug (r=0.9997),the limit of detection is 2ng(S/N=3). The analysis percision RSD was 0.12%,The repeatabiliy Precision RSD was 0.67%. It also established acid-base method using non-aqueous . At the same time the quality criteria for the l-Methylhydantoin was developed as well as the stability test and accelerated test of l-Methylhydantoin; the results show that l-Methylhydantoin stabilizes in front of the light, moisture, thermal.Conclusion:This thesis provides a quality standards basis for making l-Methylhydantoin Raw Materials, storage conditions and validity, at the same time, lays a foundation for the research and development of preparation and the design of production technology standards. Not only does it fill the blank of the research field of the quality control of l-Methylhydantoin at home and abroad, but also paves the way for making l-Methylhydantoin a nation-class medicine and its wider application.更多还原