摘要：本课题旨在对新药尼拉帕尼分析方法的建立。尼拉帕尼是一种聚腺苷二磷酸核糖聚合酶1/2（PARP-1和PAEP-2）抑制剂，能够抑制肿瘤细胞DNA的修复，达到治疗癌症的疗效。由于高效液相色谱在医药领域中有着广泛的应用，本文主要使用高效液相色谱仪进行原料药尼拉帕尼分析方法的建立，文章第一部分介绍了以下对尼拉帕尼高效液相色谱条件的筛选：紫外检测波长、检测样本溶液的浓度、色谱柱种类、色谱柱温度、进样流速、进样体积、流动相的成分及比例。经过一系列单因素对比实验，筛选出了最优的色谱条件。在文章第二部分对已建立的尼拉帕尼分析方法进行方法学验证，通过验证系统适应性、方法精密度、准确度和溶液稳定性验证，证明色谱条件：色谱柱AgilentZORBAXSB-C185μm4.6×250mm；柱温30℃；流速1.0mg·mL-1；进样量5μL；检测波长265nm；乙腈-水（35%-65%）（v/v）等度洗脱20min是尼拉帕尼最佳分析条件。

关键词：尼拉帕尼；高效液相色谱；色谱条件；方法验证

The Study on Chromatographic Analysis Methods of Niraparib

Abstract: This project aims at the establishment of an analytical method for the new drug Niraparib. Niraparib is an inhibitor of poly (ADP-ribose) polymerase 1/2 (PARP-1 and PAEP-2) that inhibits the repair of tumor DNA and achieves therapeutic efficacy for cancer. Since HPLC has a wide range of applications in the medical field, this article mainly uses HPLC to establish the analytical method. The first part of the article introduced the following screening conditions for HPLC: UV detection wavelength, detection of sample solution Concentration, column type, column temperature, injection flow rate, injection volume, mobile phase  composition and ratio. After a series of single factor comparison experiments, the optimal chromatographic conditions were screened out. In the second part of the article, the established analytical methods were validated by methodology, and the verification of system suitability, method precision, accuracy, and solution stability was verified to prove the chromatographic conditions: Instrument: Diane Ultimate3000 HPLC; Chromatography Column Agilent ZORBAX SB-C18 5μL 4.6x250nm; column; 30 °C; the flow rate 1.0 ml·min-1; injection volume 5 μL; detection wavelength 265 nm; acetonitrile-water (35-65%) (v/v) isocratic 20 min is the best analytical condition for Niraparib.

Keywords: Niraparib; High Performance Liquid Chromatography (HPLC); Chromatographic conditions; Method Validation

目录

1绪论 5

1.1尼拉帕尼简介 5

1.2尼拉帕尼的药理信息 5

1.2.1尼拉帕尼的作用机理 5

1.2.2尼拉帕尼的适用人群 6

1.2.3尼拉帕尼的毒性和不良反应 6

1.3尼拉帕尼的合成路线 6

1.4高效液相色谱在医药领域的应用 7

1.5高效液相色谱的工作原理 7

1.5.1基本原理 7

1.5.2反向键合相色谱法分离原理 8

1.5.3高效液相色谱中流动相的选择 9

1.5.4高效液相色谱色谱柱柱效的评价 9

1.5.5高效液相色谱与其他色谱分析相比的优点···········9

1.6课题研究思路 10

1.7研究目的与意义