基因毒性杂质甲磺酸酯稳定性及水解反应动力学研究

目的:在痕量水平基因毒性杂质甲磺酸酯(甲磺酸甲酯、甲磺酸乙酯、甲磺酸丙酯和甲磺酸异丙酯)的稳定性及水解动力学研究。方法:以乙腈-水(80∶20,v/v)为溶剂配制甲磺酸酯混合溶液,分别置于298、313及323 K温度下,定时取样并加入碘化钠衍生化溶液,分别得到相应的碘代烷烃(碘甲烷、碘乙烷、碘丙烷和碘代异丙烷),采用顶空法进行气相色谱-质谱测定。结果:甲磺酸乙酯和甲磺酸丙酯在上述不同温度下均具有较好的稳定性,而甲磺酸甲酯和甲磺酸异丙酯仅在室温条件下具有较好的稳定性。随着温度升高至313 K和323 K,甲磺酸甲酯和甲磺酸异丙酯均发生了酯基水解反应,并测得相应的水解反应动力学参数。结论:通过本研究揭示了不同甲磺酸酯的稳定性属性,并由此提示了在检测方法学开发中应特别留意甲磺酸酯溶液放置温度条件的控制,以保证检测结果的准确性。

Study on the stability and hydrolysis kinetics of genotoxic impurities methanesulfonates

Objective:To study the stability and hydrolysis kinetics of genotoxic impurities methanesulfonates at trace levels,including methyl methanesulfonate(MMS),ethyl methanesulfonate(EMS),propyl methanesulfonate(PMS)and isopropyl methanesulfonate(IMS).Methods:Solutions of methansulfonates were prepared in acetonitrile/water(80∶20,v/v)and placed under 298 K,313 K and 323 K,respectively.The methanesulfonates solutions were transformed into corresponding alkyl iodides for headspace GC/MS detection by utilizing the sodium iodide solution as the derivative reagent.The concentrations of the methansulfonates were monitored periodically by their corresponding derivative products of alkyl iodides.Results:EMS and PMS were stable under the above mentioned temperatures,while MMS and IMS were found to be stable only under 298 K.As the temperature raised to 313 K and 323 K,both MMS and IMS degraded due to the hydrolysis reaction on their corresponding ester groups.Both the hydrolysis kinetic parameters were obtained.Conclusion:Different kinds of methanesulfonates possess characteristic stability properties,whereas,indicating that serious attentions should be paid on the strict requirements of the temperature control for preparing the sample solutions during assay determinations.