GC法测定[4-(4-氟苯基)-6-异丙基-2-(N-甲基-N-甲磺酰基氨基)嘧啶-5-基]甲醇中的残留溶剂

Determination of Residual Organic Solvents in 4-(4-fluorophenyl)-6-isopropyl-2-[(N-methyl-N-methyl-sulfonyl)amido] pyriminl-5-yl-methanol by GC

目的:建立以气相色谱法测定瑞舒伐他汀中间体[4-(4-氟苯基)-6-异丙基-2-(N-甲基-N-甲磺酰基氨基)嘧啶-5-基]甲醇中乙醇、丙酮、二氯甲烷、正己烷、乙酸乙酯、甲苯和N,N-二甲基甲酰胺(DMF)残留量的方法。方法:以二甲基亚砜为溶剂,苯为内标,在DB-624毛细管柱上分离各组分,用氢火焰离子化检测器检测,柱温采用程序升温,载气为氮气,流速为1.0mL·min-1,进样口温度为220℃,检测器温度为250℃,分流比为10:1。结果:乙醇、丙酮、二氯甲烷、正己烷、乙酸乙酯、甲苯和DMF的检测浓度线性范围分别为25.0～350.0、24.9～348.6、3.2～44.8、1.6～22.4、24.1～337.4、4.5～63.0、5.4～75.6μg·mL-1(r>0.995),平均回收率为83.7%～113.8%,日内RSD小于4.2%,日间RSD小于4.6%。样品中乙醇、丙酮、二氯甲烷、DMF均未检出,其余溶剂均不超过限量。结论:该方法操作简便,准确度高,适用于[4-(4-氟苯基)-6-异丙基-2-(N-甲基-N-甲磺酰基氨基)嘧啶-5-基]甲醇中残留溶剂的检测。

OBJECTIVE： To develop GC method for the content determination of residual organic solvents in 4-（4-fluorophenyl）-6-isopropyl-2-[（N-methyl-N-methylsulfonyl）amido] pyriminl-5-yl-methanol, such as ethanol, acetone, dichloromethane, N-hexane, ethyl ether, methylbenzene and N, N-dimethylformamide. METHODS： Using dimethyl sulfoxide as the solvent and benzene as the internal standard, the determination was performed on a DB-624 capillary column with temperature program. FID was used as detector and nitrogen was used as carrier. The flow rate was set at 1.0 mL·min^-1, and the inlet temperature was 220 ℃. The temperature of detector was set at 250 ℃ and the split ratio was 10：1. RESULTS： The linear ranges were 25.0-350.0 μg·mL^-1 for ethanol, 24.9-348.6 μg·mL^-1 for acetone, 3.2-44.8 μg·mL^-1 for dichloromethane, 1.6-22.4 μg·mL^-1 for N-hexane, 24.1-337.4 μg·mL^-1 for ethyl ether, 4.5-63.0 μg·mL^-1 for methylbenzene and 5.4-75.6 μg·mL^-1 for N, N-dimethylformamide （r〉0.995）. The average recoveries ranged from 83.7% to 113.8%. Intra-day RSD was less than 4.2% and inter-day RSD was less than 4.6%. Ethanol, acetone, dichloromethane and DMF hadn＇t been detected in samples and the quantity of other solvents met the standard. CONCLUSION： The method is convenient, accurate and suitable for the determination of residual organic solvents in 4-（4-fluorophenyl）-6-isopropyl-2-[（N-methyl-N-methylsulfonyl）amido] pyriminl-5-yl-methanol.