【作者】 杨婷；

【导师】 姚军； 高晓黎；

【作者基本信息】 新疆医科大学 ， 药学（专业学位）， 2022， 硕士

【摘要】 目的:1)建立结合雌激素乳膏的前处理方法并验证高效液相色谱法对乳膏中两种主要成分雌酮硫酸钠（Es）和马烯雌酮硫酸钠（Eqs）的含量测定方法;2)考察建立的乳膏前处理方法对其60个甾族化合物（60ID）提取率的影响;3)考察乳膏中各辅料与原料药是否相容。方法:1)Agilent C₁₈柱,（4.6mm×150 nm,5μm）,乙腈-0.025mo L·L^-1磷酸二氢钾（1︰3）为流动相,波长205nm,柱温35℃,流速1.0m L·min^-1,以离心后乳膏中油相基质和水相基质的分层情况和Es和Eqs的含量测定为指标,建立乳膏的前处理方法,通过方法学考察建立的乳膏质量控制方法;2)利用液相色谱-质谱联用（LC-MS）检测方法比较两种前处理方法对乳膏中60ID提取率的差异;3)采用影响因素试验方法对辅料进行筛选,考察乳膏中各辅料与原料药是否相容。结果:1)实验建立的高速离心法对乳膏中Es和Eqs的提取率较好,该方法标准曲线线性良好,专属性、精密度及重复性等满足中国药典2015版规定;2)通过比较两种前处理方法对乳膏中60ID提取率,发现实验建立的高速离心法对乳膏中60ID提取率较好,提取率均大于70%;3)通过原辅料相容性实验发现样品放置30天以后十六醇、单硬脂酸甘油酯对Eqs的含量有影响;丙二醇单硬脂酸酯对Es的含量有影响,其他辅料与原料药的相容性较好。结论:1)本研究建立的乳膏前处理方法对Es和Eqs的含量测定准确度高,精密度和灵敏度均能满足测定要求,适用于乳膏中Es和Eqs的含量测定,为乳膏质量控制提供科学依据;2)通过原辅料相互作用实验,可以为制定提高结合雌激素乳膏在高温条件和高湿条件下的稳定性措施和处方筛选提供科学依据。更多还原

【Abstract】 Objectives:1)Establish a pretreatment method combining estrogen cream,establish and verify the determination of two main components（Es and Eqs）in the cream by high performance liquid chromatography;2)review the established cream pretreatment The effect of the method on its 60ID extraction rate;3)To investigate whether the excipients in the cream are compatible with the drug substance.Methods:1)Agilent C18 column（4.6mm×150 nm,5μm）,acetonitrile-0.025mo L·L^-1potassium dihydrogen phosphate（1:3）as mobile phase,wavelength 205nm,column temperature 35℃,flow rate 1.0m L·min^-1,based on the delamination of the oil phase matrix and the water phase matrix and the content of Es and Eqs in the cream after centrifugation as indicators,establish a pretreatment method for the cream,and establish a cream quality control method through methodological inspection;2)The LC-MS detection method was used to compare the effect of two pretreatment methods on the extraction rate of 60ID in the cream.3)The influential factor test method was used to screen the excipients to check whether each excipient in the cream was compatible with the drug substance.Results:1)The experimentally established high-speed centrifugation method has a good extraction rate of Es and Eqs in the cream.The standard curve of the method is good,and the specificity,precision and repeatability meet the requirements of the 2015 edition of the Chinese Pharmacopoeia;2)By comparison Two pre-treatment methods were used to extract the60ID in the cream.It was found that the high-speed centrifugation method established in the experiment had a good extraction rate for the 60ID in the cream,and the extraction rates were greater than 70%.3)It was found that the sample was placed at 30 After sixteen days,cetyl alcohol and glyceryl monostearate have an effect on the content of Eqs;propylene glycol monostearate has an effect on the content of Es,and other excipients have better compatibility with the drug substance.Conclusions:1)The cream pretreatment method established in this study has high accuracy for the determination of Es and Eqs,and the precision and sensitivity can meet the measurement requirements.It is suitable for the determination of Es and Eqs in creams,which is the quality of creams.Control provides scientific basis;2)Through raw material and auxiliary material interaction experiments,it can provide scientific basis for formulating measures and prescription screening to improve the stability of combined estrogen cream under high temperature and high humidity conditions.更多还原