HPLC法检测托吡司特中的基因毒性杂质对甲苯磺酸异丙酯、对甲苯磺酸仲丁酯、对甲苯磺酸乙酯  

Determination of genotoxic impurities isopropyl p-toluensulfonate,sec-butyl p-toluenesulfonate and ethyl p-toluenesulfonate in topiroxostat by HPLC

作　　者：谢卫锋 高玉珍 XIE Wei-feng;GAO Yu-zhen(Taizhou Jinhong Pharmaceutical Technology Co.,Ltd.,Taizhou 225300,China)

机构地区：[1]泰州锦鸿医药科技有限公司,泰州225300

出　　处：《药物分析杂志》2018年第10期1788-1793,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立一种高效液相色谱测定托吡司特的基因毒性杂质对甲苯磺酸异丙酯(杂质H)、对甲苯磺酸仲丁酯(杂质I)和对甲苯磺酸乙酯(杂质J)的方法。方法:采用C18色谱柱(100 mm×4.6 mm,3.5μm),以水为流动相A,乙腈为流动相B,进行梯度洗脱,流速0.8 mL·min^(-1),检测波长220 nm,柱温40℃。结果:杂质H、I及J质量浓度分别在0.050～0.202μg·m L^(-1)(R2=0.999 7)、0.048～0.192μg·m L^(-1)(R2=0.999 8)及0.051～0.204μg·m L^(-1)(R2=0.999 5)范围内与峰面积呈良好线性关系,定量下限分别为0.050 5、0.048 0和0.051 0μg·m L^(-1),检测下限分别为0.016 7、0.015 8和0.016 8μg·mL^(-1),平均回收率分别为99.3%(RSD=1.9%)、103.0%(RSD=1.2%)和98.2%(RSD=1.6%)。3批样品中均未检出基因毒性杂质H、I及J。结论:本法适用于托吡司特中的基因毒性杂质H、I及J的检测及限度控制。Objective：To establish an HPLC method for the determination of genotoxic impurities isopropyl p-toluensulfonate（impurity H）, sec-butyl p-toluenesulfonate（impurity I） and ethyl p-toluenesulfonate（impurity J） in topiroxostat.Methods：The method was achieved on a C18 column（100 mm×4.6 mm, 3.5 μm）;the mobile phase consisted of water（A） -acetonitrile（B） with gradient elution at a flow rate of 0.8 mL·min-1;the detection wavelength was 220 nm, and the column temperature was 40℃.Results：Good linear relationships between the mass concentrations and the peak areas of impurities H, I, and J in the ranges of 0.050-0.202 μg·mL^-1（R2=0.999 7）, 0.048-0.192 μg·mL^-1（R2=0.999 8）, and 0.051-0.204 μg·mL^-1（R2=0.999 5） were achieved.The limits of quantification were 0.050 5 μg·mL-1, 0.048 0 μg·mL^-1 and 0.051 0 μg·mL^-1, respectively.The limits of detection were 0.016 7 μg·mL^-1, 0.015 8 μg·mL^-1 and 0.016 8 μg·mL^-1, respectively.The average recoveries were 99.3%（RSD=1.9%）, 103.0%（RSD=1.2%） and 98.2%（RSD=1.6%）, respectively.No genotoxic impurities H, I and J were detected in three batches of samples.Conclusion：This method is applicable to the detection and limit control of genotoxic impurities H, I, and J in topiramate.

关 键 词：高效液相色谱法 托吡司特 基因毒性杂质 对甲苯磺酸异丙酯 对甲苯磺酸仲丁酯 对甲苯磺酸乙酯 

分 类 号：R917[医药卫生—药物分析学]