目的:利用电喷雾电离串联质谱监测合成帕拉米韦的反应副产物,推测副产物化学结构及相对含量,为快速改进帕拉米韦的合成工艺提供依据。方法:以文斯内酰胺为初始原料,经催化开环、氨基保护、开环加成等多步反应合成帕拉米韦三氟乙酸盐。质谱条件:质谱采用电喷雾正离子模式(ESI+),质量扫描范围为m/z50～800。反应终溶液经甲醇稀释直接测定,并测定一级质谱中主要离子的二级质谱。结果:反应终溶液的ESI-MS谱中,主要为m/z329.0及313.1的2个峰,分别是目标化合物帕拉米韦及其脱氧反应副产物的[M+H]+峰。脱氧副产物的含量约为帕拉米韦的80%。结论:利用电喷雾电离串联质谱监测帕拉米韦合成反应,可快速推测反应副产物化学结构及其相对含量,为改进其合成工艺提供重要依据。 OBJECTIVE: To monitor the reaction by-products of the formulation of peramivir by electrospray ionization tandem mass spectrometry, and to estimate the chemical structure and relative content of the by-products, so as to provide a basis for the rapid improvement of the synthesis process of the peramivir. Methods: Vasilactam was used as the starting material to synthesize the peramivir trifluoroacetate by several steps such as catalytic ring opening, amino protection and ring opening addition. Mass Spectrometry Conditions: The mass spectrometry was electrospray positive ion mode (ESI +) with a mass scan range of m / z 50-800. The final solution of the reaction was directly diluted with methanol and the secondary mass spectra of the major ions in the first-order MS were determined. Results: The two peaks of m / z 329.0 and 313.1 in the final solution of the reaction were peaked at [M + H] + of the target compound peramivir and its deoxygenation by-products, respectively. The content of deoxygenated by-products is about 80% of that of peramivir. Conclusion: The electrochemiluminescence ionization tandem mass spectrometry (ESI-MS / MS / MS) is used to monitor the synthesis of peramivir. The chemical structure and relative content of the reaction by-products can be rapidly estimated, which provides an important basis for improving the synthesis process.