盐酸地芬尼多中溴乙烷等溶剂残留的检测

Determination of residual solvents in difenidol hydrochloride

目的建立顶空气相色谱法(GC)测定盐酸地芬尼多原料药中的残留溶剂溴乙烷、乙醇、四氢呋喃。方法 DB-624石英毛细管柱;升温程序:初始温度50℃,5℃·min^(-1)升温至120℃,保持4min,再以25℃·min^(-1)升温至180℃,保持2 min;FID检测器,温度250℃;进样口温度150℃;载气(N_2)流速3.0 mL·min^(-1);以水作为溶剂,顶空进样,平衡温度85℃,平衡时间20 min;定量环体积1 mL;分流比15∶1。结果溴乙烷、乙醇、四氢呋喃检测浓度的线性范围分别为2.146~85.85(r=0.9990)、12.69~507.7(r=1.000)、1.801~72.03(r=1.000)μg·mL^(-1);平均回收率为92.0%~95.3%,RSD为1.2%~2.0%。结论本方法简单、准确、灵敏度高、重复性好,可作为盐酸地芬尼多原料药中有机溶剂残留量的控制方法。

Objective To establish a headspace GC method to determine the content of 3 residual organic solvents （bromoethane, ethanol and tetrahydrofiaran） in difenidol hydrochloride. Methods The residual organic solvents were separated on DB-624 capillary column. The column temperature was raised from 50℃ to 120℃ at the rate of 5℃·min^-1, and kept for 4 min by program. The temperature was raised to 180℃ at the rate of 25℃·min^-1, kept for 2 min by program. FID was used as the detector at 250℃, and the injector temperature was 150℃. Nitrogen was used as the carrier at the flow rate of 3.0 mL·min^-1, and water was used as the solvent. The equilibrium temperature was 85 ℃ and lasted 20 min. The volume of dosing ring was 1 mL, and the split ratio was 15 ： 1. Results The linear ranges of bromoethane, ethanol and tetrahydrofuran were 2.146 - 85.85 μg·mL^-1 （r = 0.9990）, 12.69 - 507.7μg·mL^-1 （r = 1.000）, and 1.801 - 72.03μg·mL^-1 （r = 1.000）, respectively. The average recoveries ranged from 92.0% to 95.3% with RSD at 1.2% - 2.0%. Conclusion The method is simple, accurate, sensitive and reproducible, and can be used as the control method for the determination of residual organic solvents in difenidol hydrochloride.