赛乐西帕中甲磺酸酯杂质的来源分析与检测

Source Analysis and Detection of Mesylate Impurities in Selexipag

本文通过总结赛乐西帕不同合成策略,分析赛乐西帕中甲磺酸甲酯(MMS)、甲磺酸乙酯(EMS)和甲磺酸异丙酯(IMS)的可能来源,针对性开发衍生化HS-GC-MS方法检测赛乐西帕原料药中MMS、EMS和IMS含量,并完成方法验证。该方法具有灵敏度高、重复性好等优点,能满足检测要求。利用此方法对赛乐西帕样品进行检测,结果证实赛乐西帕合成过程中存在产生MMS、EMS和IMS并最终残留在API中的可能。

In this paper, the possible sources of methyl methanesulfonate(MMS), ethyl methanesulfonate(EMS) and isopropyl methanesulfonate(IMS) in selexipag were analyzed by summarizing different synthetic strategies of selexipag. Targeted development of a derivatized HS-GC-MS method to detect the contents of MMS, EMS and IMS in selexipag, and completed the method validation. The method has the advantages of high sensitivity and good repeatability, and can meet the detection requirements. This method was used to detect selexipag samples, and the results confirmed that they may be generated during the synthesis of selexipag and eventually remain in the API.