雷替曲塞相关杂质的合成及血液系统毒性的研究

Synthesis and Evaluation of the Toxicity of Raltitrexed-Related Impurities to the Blood System

报道了一种雷替曲塞相关杂质的制备方法,并研究了相关杂质对于血液系统的影响。结果表明,本方法条件温和,收率较高,所制得的杂质A、B和C质量稳定,可用于制备雷替曲塞有关杂质分析的对照品。本文还研究了杂质A、B和C对于血液细胞的影响,结果表明,杂质A、B和C会导致白细胞及粒细胞较为显著地减少,其对于血液系统的毒性显著高于雷替曲塞。因此,本文提供的高纯度杂质A、B和C的制备方法,可为雷替曲塞的质量控制提供了理论依据。

In this paper,a preparation method of raltitrexed-related impurities was reported,and the effect of related impurities on blood system was studied.The results showed that the method has mild conditions and high yield.The prepared impurities A,B and C are stable quality and can be used to prepare reference materials for the analysis of raltitrexed-related impurities.The effects of impurities A,B and C on blood cells were also studied.The results showed that impurities A,B and C could significantly reduce the number of leukocytes and granulocytes,and their toxicity to the blood system was significantly higher than that of raltitrexed.Therefore,the preparation method of high purity impurities A,B and C can lay a solid foundation for quality research of raltitrexed.