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摘要：目的：对CA4药物进行处方前研究，并对其理化参数进行测定。方法：建立HPLC测定CA4的含量分析方法， Waters Atlantis C18柱（250mm×4.6mm，5μm）；流动相：水-甲醇（32:68）；检测波长为 295nm，流速为0.8mL/min，柱温为30℃，进样量为 20μL。测定CA4在不同极性溶剂中的溶解度，考察CA4的油水分配系数，并对其湿度进行研究从而完善药物的处方前研究。结果：CA4浓度在2.078~12.468ug/ml范围内有良好的线性关系（r=0.9998），精密度、稳定性良好，符合CA4定量测定的要求。通过研究CA4的吸湿性，得到其湿度为8.5%；通过摇瓶法，在不同极性溶剂中测定CA4的溶解度，溶剂的极性由大到小，其溶解度却表现出增大趋势；通过考察CA4的油水分配系数，发现在碱性环境中，其亲脂性较强，中性环境中，其 lgP 随pH的增大而增大，酸性环境中，其亲脂性较差。结论：依据系统的方法学验证，为CA4药物的处方筛选、质量研究等，提供精准的检测方法。24359
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毕业论文关键词：CA4；平衡溶解度；解离常数；油水分配系数；相容性
Preformulation Study on CA4
ABSTRACT: Objective:Study on CA4 prescription drugs, and measure their physical and chemical parameters. Methods:To establish the HPLC determination of CA4 content. Using reverse phase C18 column (Waters Atlantis C18 column (250mm × 4.6mm 5μm)); mobile phase: water - methanol (32:68); detection wavelength was 295nm, the flow rate was 0.8mL/min, column temperature was 30 ℃, into The injection volume was 20uL. study the solubility of CA4 solvents of different polarity,tese oil-water partition coefficient of CA4, and conduct research in order to improve its humidity prescription drugs before the study. The results: CA4 concentration had a good linear relationship in the range of 2.078 ~ 12.468ug/ml (R = 0.9998), Precision, good stability, in line with the requirements CA4 quantitative determination. By studying CA4 hygroscopicity obtain a moisture of 8.5%; By shake flask-HPLC method, Found CA4 solubility in solvents of different polarity, as the descending polar solvent, the solubility is increased successively; By examining CA4 of water partition coefficient, found in an alkaline environment, and its lipophilic strong, neutral environment, which lgP with the increase of pH, the acidic environment, its poor lipophilic. Conclusion: The method was validated by the system, so as prescription drug screening, the quality and stability of research, to provide accurate, precise, stable detection methods.
KEY WORDS：CA4; equilibrium solubility; dissociation constant; oil-water partition coefficient; compatibility
目录
1
1 前言 1
1.1立项依据 1
1.2处方前研究的必要性 2
1.2.1 新化学实体的液态表征 2
2文献综述 4
2.1模型药物CA4简介 4
2.2 外观性状 5
2.3 CA4作用机理 5
2.4 药代动力学方面的特点 6
2.5毒性及不良反应特点 6
2.6 目前国外临床研究状况 7
3 实验部分 9
3.1 仪器与试药 9
3.1.1 仪器 9
3.1.2 试药 9
3.2 HPLC法测定CA4方法学的建立 10
3.2.1 检测波长的确定 10
3.2.2 色谱条件 10
3.2.3 系统适应性试验 11
3.2.4 线性试验 12
3.2.5 定量限试验 13
3.2.6 检测限试验 13
3.2.7精密度试验 14
3.2.8 样品溶液的稳定性试验 15
3.3 CA4吸湿性研究 16