硫酸氢氯吡格雷有关物质的合成及工艺应用

Synthesis of Related Substances of Clopidogrel Bisulfate and the Innovation of Synthesis Process

硫酸氢氯吡格雷是一种通过抑制血小板聚集高效的抗血栓药物,临床上主要用于治疗动脉粥样硬化引起的心脏病或中风。有关物质的研究是药品质量研究中关键性项目之一,其含量是评价药品的纯度是否合格的重要指标。结合硫酸氢氯吡格雷成熟合成路线,分析了3个潜在的硫酸氢氯吡格雷的有关物质,并利用硫酸氢氯吡格雷合成过程所用到的原料、中间体或成品进行了合成制备,通过1 H NMR、13C NMR、HRMS对产物的结构进行表征与确证。结合3个有关物质的监测结果,对硫酸氢氯吡格雷的进一步工艺优化提出建议。

Clopidogrel bisulfate is a highly effective antithrombotic drug that inhibits platelet aggregation.It is clinically used to treat heart disease or stroke caused by atherosclerosis.The research of related substances is the key item in the research of drug quality,and it is an important index to evaluate whether the purity of the drug is qualified.Combined with the synthesis route of clopidogrel bisulfate,three potential related substances of clopidogrel bisulfate were analyzed and prepared from the raw materials,intermediates or finished products used in the synthesis process of clopidogrel bisulfate.The structures of three related substances were characterized by 1 H NMR,13C NMR and HRMS.Combined with the monitoring results of three related substances,the process improvement for the synthesis of clopidogrel bisulfate was proposed.