艾司西酞普兰原料药中未知杂质的结构鉴定

目的: 鉴定艾司西酞普兰原料药中一未知杂质的结构。 方法: 基于LC-MS(MSⁿ)分析在线鉴定未知杂质结构;采用制备色谱分离目标杂质单体化合物,再基于NMR表征进一步确认目标杂质结构;最后结合工艺,揭示了杂质产生的来源,并指导工艺消除杂质。 结果: 该杂质为(S)-1-(3-二甲基-乙基-氨基)-丙基-1-(4-对氟苯基)-1,3-二氢-5-异苯并呋喃腈。 结论: 本研究为艾司西酞普兰原料药的工艺研发及质量研究提供指导。

Objective: To identify one unknown impurity in drug substance of escitalopram. Methods: The structure of the studied impurity was identified by LC-MS(MSⁿ)on-line,and was further confirmed by preparative HPLC isolation and subsequent NMR analysis.Finally,the mechanism of the formation of the impurity was revealed with regard to product process,and the impurity was successfully avoided in the final product by process control. Results: The studied impurity was identified as(S)-3-(5-cyano-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl)-N-ethyl-N,N-dimethylpropan-1-aminium. Conclusion: The study provided valuable indications for both process development and quality study of drug substance of escitalopram.

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7 USP 34-NF 29.2011.4957