艾拉莫德杂质标定及其方法学验证

论文总字数：18117字

摘 要

目的：创建简单有效，精准方便的高效液相色谱方法，可用于艾拉莫德杂质M10和杂质M12含量的标定，而且对该标定方法进行验证。

方法：流动相A为40mmol/L的磷酸二氢铵溶液，流动相B为乙腈；采用线性梯度进行洗脱；溶剂为乙腈:甲醇:水=（5:3:2）；色谱柱为Phenomenex Gemini C18 New Column柱（250*4.6mm*5um）；柱温为30℃；检测波长为270nm；流速为1.0mL/min；进样量为20ul。

结果：根据试验结果可知，溶剂均不干扰艾拉莫德杂质M10及M12的检测；杂质M10和M12制备后室温放置32h内稳定性良好；中间精密度试验杂质M10的RSD为0.17%、M12的RSD为0.01%（n=6），中间精密度试验结果良好；重复性试验杂质M10的RSD为0.06%、M12的RSD为0.01%（n=6），重复性试验结果良好。得出杂质M10和M12的含量分别为97.26%和99.85%，这个结果符合了杂质对照品对于纯度的要求。

结论：艾拉莫德杂质M10及M12的标定方法简单、快速、准确。

关键词：HPLC；方法学验证；杂质标定；艾拉莫德

Calibration and Methodology Validation of Iguratimod Impurity

Abstract

Objective:To establish a simple, effective, accurate and convenient HPLC method, which can be used for the calibration of iguratimod impurity M10 and impurity M12 content, and validate the calibration method.

Methods: Mobile phase A is 40mmol/L phosphoric acid two ammonium hydrogen solution, mobile phase B is acetonitrile; linear gradient is adopted; solvent is acetonitrile: methanol: water = (5:3:2); chromatographic column is Phenomenex Gemini C18 New Column column(250*4.6mm*5um) ;the column temperature is 30 ℃; the detection wavelength is 270nm; the flow rate is 1.0mL/min; the injection volume is 20ul.

Results: According to the experimental results, both solvents do not interfere with the detection of iguratimod impurity M10 and M12; M10 and M12 impurities after preparation for 32H at room temperature in good stability test; impurities precision middle M10 RSD 0.17%, M12 RSD 0.01% (n=6), intermediate precision test results good repeatability; impurity M10 RSD 0.06%, M12 RSD 0.01% (n=6), repeatability of test results is good.The content of impurity M10 and M12 was found to be 97.26% and 99.85% respectively.The results are in accord with the requirements for purity of impurities.

Conclusion: the calibration method iguratimod of impurity M10 and M12 is simple, rapid and accurate.

Key words: HPLC;Methodology validation;Impurity calibration;iguratimod

目 录

摘要.......................................................................................................................................................................Ι

Abstract.................................................................................................................................................................Π

第一章 前言 1

1.1高效液相色谱仪检测技术（HPLC）....................................................................................................1

1.1.1高效液相色谱法简单介绍和发展情况 1

1.1.2高效液相色谱法在药物分析里面的应用...................................................................................1

1.2杂质对照品..............................................................................................................................................2

1.2.1杂质对照品简介...........................................................................................................................2

1.2.2杂质对照品的标定项目...............................................................................................................2

1.3药品质量控制分析方法的验证 2

1.3.1专属性 2

1.3.2 样品溶液稳定性...........................................................................................................................2

1.3.3重复性 3

1.3.4中间精密度 3

1.4 艾拉莫德杂质M10和M12的研究概况 3

1.5本课题的研究内容 3

第二章 分析方法的建立 4

2.1实验材料 4

2.2试验方法讨论 5

2.2.1溶剂的选择 5

2.2.2检测波长的选择 5

2.2.3色谱条件的设定...........................................................................................................................5

2.3本章结论 6

第三章 杂质标定 7

3.1溶液配制 7

3.2色谱条件 7

3.3试验方法..................................................................................................................................................7

3.4结果..........................................................................................................................................................8

第四章 方法学验证 10

4.1方法学验证的内容 10

4.2试验条件 10

4.2.1溶液配制.....................................................................................................................................10

4.2.2 色谱条件....................................................................................................................................10

4.3方法学验证的结果 11

4.3.1专属性 11

4.3.2溶液稳定性.................................................................................................................................12

4.3.3重复性.........................................................................................................................................13

4.3.4中间精密度.................................................................................................................................13

4.4本章结论 15

第五章 结论........................................................................................................................................................16

致谢......................................................................................................................................................................17

参考文献..............................................................................................................................................................18

第一章 前言

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