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Determination of Genotoxic Impurities in Safinamide Mesylate by LC/MS
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摘要: 甲磺酸沙非胺主要用于治疗帕金森病，建立了甲磺酸沙非胺中基因毒性杂质（（S）-4-（（（1-氨基-1-氧丙烷-2-甲基）氨基）甲基）苯甲磺酸酯）的液相色谱-质谱联用检测方法。样品溶于甲醇，经YMC-Triart C18(4.6 mm×100 mm, 3μm)分离，0.1 %甲酸水和0.1 %甲酸甲醇梯度洗脱，采用多反应监控（MRM）模式正离子扫描进行定量检测。该方法具有较好的专属性，目标化合物在1.53～30.54 ng/mL的浓度范围内线性关系良好（R2>0.99）；检出限为0.76 mg/kg，定量限为1.53 mg/kg；加标回收率为98.5%～99.90 %，RSD为0.83%～2.10%。该方法灵敏度高，准确可靠，可应用于甲磺酸沙非胺的质量监控。Abstract: Safinamide mesylate is mainly used in the treatment of Parkinson's disease. A liquid chromatography-mass spectrometry (LC-MS) method was developed for the determination of genotoxic impurities ((S)-4-((1-amino-1-oxopropane-2-methyl)amino)methyl)benzoate) in safinamide mesylate. The sample was dissolved in methanol, separated by YMC-Triart C18 column (4.6mm×100 mm, 3μm), eluted with 0.1 % formic acid in water and 0.1 % formic acid in methanol gradient, and quantified by positive ion scanning in multiple reaction monitoring (MRM) mode. The method has good specificity, and the target compound has a good linear relationship in the concentration range of 1.53-30.54 ng/mL. Standard recovery rate was 98.5%～99.90% with relative standard deviations of 0.83%～2.10%. The linear response range was between 1.53～30.54 ng/mL (R2 >0.99). The results showed that the method was sensitive, accurate, reliable and suitable for screening of genotoxic impurities ((S) - 4 - ((1-amino-1-oxopropane- 2-methyl) amino) methyl) in safinamide mesylate.
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图 2 杂质O的准确度（n=9）
Figure 2. The accuracy of Impurity O with different concentrations (n=9)
表 1 杂质O的检出限和定量限
Table 1. The LODs and LOQs of Impurity O
检出限 定量限 检出限（ng/mL） 相当于供试品浓度（mg/kg） 定量限（ng/mL） 相当于供试品浓度（mg/kg） 0.76 0.76 1.53 1.53 
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表 2 杂质O定量限的重复性（n=6）
Table 2. The repeatability of LOQs of Impurity O (n=6)
响应值 平均值 RSD（%） 1 2 3 4 5 6 10218 9416 9121 9102 9146 9151 9359 4.66
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表 3 杂质O的标准曲线及相关系数
Table 3. The linear range, linear equation, correlation coefficient of Impurity O
线性范围（ng/mL） 回归方程 R2 1.53～30.54 y=5064.1x+3074 0.9976
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表 4 杂质O的精密度（n=6）
Table 4. The precision of Impurity O (n=6)
响应值 平均值 RSD（%） 1 2 3 4 5 6 77810 78183 79174 81357 79158 80675 79393 1.74
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表 5 杂质O的耐用性（n=7）
Table 5. The durability of Impurity O under different conditions (n=7)
方法条件 响应值 原方法 82329 柱流量0.65 mL/min 80347 柱流量0.55 mL/min 89499 柱温33℃ 85154 柱温27℃ 81503 B相初始值4% 81643 B相初始值6% 82494 平均值 83281 RSD（%） 3.74
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