HS-GC-MS同时测定沙芬酰胺中磺酸酯类基因毒性杂质

Simultaneous Determination of Sulfonate Esters of Genotoxic Impurities in Safinamide by HS-GC-MS

关键词:  沙芬酰胺  磺酸酯类  基因毒性杂质  顶空进样气相色谱-质谱联用  在线衍生

Key words:  safinamide  sulfonate esters  genotoxic impurities  HS-GC-MS  online derivation

摘要:

目的 建立同时测定沙芬酰胺原料药中5种磺酸酯类基因毒性杂质（甲磺酸甲酯、甲磺酸乙酯、甲磺酸异丙酯、甲磺酸丙酯、甲磺酸丁酯）的方法。方法 采用顶空进样气相色谱-质谱联用法，在线衍生，RESTEK Rxi-624Sil毛细管柱（30 m×0.25 mm，1.4 μm），四级杆质量检测器，离子化模式为电子轰击离子化（EI）模式，采集模式为选择离子监测。结果 5种杂质检测限为0.3~1.3 ng·mL^-1，定量限为0.9~4.3 ng·mL^-1；精密度、稳定性、重复性试验的RSD均<5%；浓度在5~300 ng·mL^-1内，5种杂质的峰面积与其相对应的浓度有良好的线性关系，相关系数（r²）均>0.995；回收率为99.4%~100.6%，RSD为0.8%~2.6%（n=9）。结论 该法操作简便，重复性好，结果准确可靠，可用于沙芬酰胺中磺酸酯类基因毒性杂质的测定。

Abstract:

OBJECTIVE To establish a simultaneous determination method of five sulfonate esters of genotoxic impurities(methyl methanesulfonate, ethyl methanesulfonate, methanesulfonicacid, 1-methylethylester, propyl methanesulfonate, N-butyl methanesulfonate) in safinamide. METHODS HS-GC-MS with online derivative method was conducted. The column was RESTEK sil Rxi-624 capillary column(30 m×0.25 mm, 1.4 μm). Detector was a mass spectrometer detector, ionization mode was electron impact(EI), collection mode was selection monitoring. RESULTS The detection limit of 5 impurities were 0.3-1.3 ng·mL^-1, quantitative limit were 0.9-4.3 ng·mL^-1. The RSDs of precision, stability and reproducibility tests were all <5%. Within the concentration range of 5-300 ng·mL^-1, the peak area of the 5 impurities had a good linear relationship with the corresponding concentration, and the correlation coefficient (r²) were all >0.995. The recovery rates were 99.4%-100.6% and RSD were 0.8%-2.6%(n=9). CONCLUSION The method is simple, reproducible, accurate, and can be used for the determination of sulfonate esters of genotoxic impurities in safinamide.