Lesinurad原料药中7种有机溶剂残留的测定

目的建立同时测定Lesinurad原料药中丙酮、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、甲苯、N,N-二甲基甲酰胺(DMF)残留量的方法。方法采用气相色谱法(GC)。色谱柱为RESTEK Rtx-502.2毛细管柱,程序升温,柱温为40℃,维持2 min,以每分钟5℃的速率升温至200℃。进样口温度为180℃,检测器为氢火焰离子化检测器,检测温度为220℃,载气为氮气,流速为2.0 ml/min,分流比为20:1,直接进样,进样量为1μl。按外标法进行定量分析。结果7种残留溶剂峰分别与相邻峰分离完全。丙酮、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、甲苯和DMF的线性范围分别为100~600μg/ml(r=0.9998),12~72μg/ml(r=0.9993),5.8~34.8μg/ml(r=0.9990),100~600μg/ml(r=0.9996),14.4~86.4μg/ml(r=0.9995),6~36μg/ml(r=0.9991),17.6~105.6μg/ml(r=0.9989);定量限分别为4.8,6.1,2.9,5.0,3.6,3.0,3.9μg/ml,检测限分别为1.6,2.0,1.0,1.8,1.2,1.0,1.3μg/ml;加样回收率分别为98.63%~99.89%(RSD=0.61%,n=9),98.59%~99.94%(RSD=0.78%,n=9),97.46%~99.23%(RSD=0.76%,n=9),98.20%~99.66%(RSD=0.78%,n=9),98.34%~99.56%(RSD=0.86%,n=9),97.46%~99.96%(RSD=0.65%,n=9),97.56%~100.63%(RSD=0.82%,n=9)。结论该方法简单、准确、重复性好,可用于Lesinurad原料药中7种残留溶剂的检测。

Simultaneous Determination of Seven Organic Solvents in Lesinurad

Objective To establish a method for the simultaneous determination of acetone,dichloromethane,n-hexane,ethyl acetate,tetrahydrofuran,toluene and N,N-dimethylformamide residuals in Lesinurad API.Methods GC was performed on a RESTEK Rtx-502.2 capillary column.The column temperature was maintained at 40℃for 2 min,then increased to 200℃at a rate of 5℃/min.The inlet temperature was 180℃,the hydrogen flame ionization detector with detection temperature of 220℃was used,the high purity N2 at a flow rate of 2.0 ml/min was adopted as carrier gas,and the split ratio was set at 20:1.Direct sampling mode was adopted,with the injection volume of 1μl.Quantitative analysis was performed by external standard method.Results The measured seven solvents were separated completely.The linear range was 100-600μg/ml for acetone(r=0.9998),12-72μg/ml for dichloromethane(r=0.9993),5.8-34.8μg/ml for n-hexane(r=0.9990),100-600μg/ml for ethyl acetate(r=0.9996),14.4-86.4μg/ml for tetrahydrofuran(r=0.9995),6-36μg/ml for toluene(r=0.9993)and 17.6-105.6μg/ml for DMF(r=0.9989).The limits of quantification were 4.8,6.1,2.9,5.0,3.6,3.0,3.9μg/ml,respectively,and the limits of detection were 1.6,2.0,1.0,1.8,1.2,1.0,1.3μg/ml,respectively.The average recoveries were 98.63%-99.89%(RSD=0.61%,n=9),98.59%-99.94%(RSD=0.78%,n=9),97.46%-99.23%(RSD=0.76%,n=9),98.20%-99.66%(RSD=0.78%,n=9),98.34%-99.56%(RSD=0.86%,n=9),97.46%-99.96%(RSD=0.65%,n=9)and 97.56%-100.63%(RSD=0.82%,n=9),respectively.Conclusion The method is simple,accurate and reproducible,and can be used for the detection of seven residual solvents in Lesinurad API.