摘要
目的:建立测定吗替麦考酚酯原料中11种残留溶剂(甲醇、乙醇、丙酮、二氯甲烷、正己烷、乙酸乙酯、环己烷、甲苯、乙酸丁酯、N,N-二甲基甲酰胺、二甲苯)的方法。方法:采用毛细管气相色谱法,6%氰苯基丙基-94%二甲基聚硅氧烷为固定相的毛细管柱(DB-624毛细管柱),检测器为氢火焰离子化检测器,载气为高纯氮气,流速为3.0 ml·min^(-1),柱温采用程序升温(起始温度为35℃,维持1 min,以5℃·min^(-1)的速率升温至90℃,再以15℃·min^(-1)的速率升温至150℃,再以25℃·min^(-1)的速率升温至225℃,维持9 min),进样口温度为200℃;检测器温度为250℃,分流比为10∶1,进样量为1μl。结果:在该色谱条件下专属性高,甲醇、乙醇、丙酮、二氯甲烷、正己烷、乙酸乙酯、环己烷、甲苯、乙酸丁酯、N,N-二甲基甲酰胺、二甲苯检测线性范围分别为0.060～6.06(r=0.999 2)、0.100～10.06(r=0.999 0)、0.099～9.96(r=0.998 9)、0.012～1.256(r=0.998 7)、0.006～0.561(r=0.998 5)、0.100～10.04(r=0.998 6)、0.078～7.80(r=0.999 1)、0.017～1.73(r=0.999 0)、0.101～10.06(r=0.999 5)、0.018～1.83(r=0.998 5)、0.044～4.42 mg·ml^(-1)(r=0.998 3);平均回收率分别为97.7%(RSD=1.4%,n=9)、97.9%(RSD=1.3%,n=9)、103.2%(RSD=2.1%,n=9)、98.8%(RSD=2.2%,n=9)、99.1%(RSD=2.2%,n=9)、100.4%(RSD=4.5%,n=9)、98.5%(RSD=2.4%,n=9)、99.6%(RSD=3.3%,n=9)、98.9%(RSD=2.7%,n=9)、101.7%(RSD=4.3%,n=9)、95.2%(RSD=2.3%,n=9);检测限分别为6.06,10.06,3.32,2.51,2.24,5.02,2.60,1.73,10.07,3.65,4.42μg·ml^(-1)。结论:该方法简便、准确、可靠、灵敏,可用于吗替麦考酚酯原料中残留溶剂含量的测定。
Objective: To establish a method for the determination of 11 residual solvents (methanol,ethanol,acetone,methylene chloride,n-hexane,ethyl acetate,cyclohexane,toluene,butyl acetate,N,N-dimethylformamide and xylene) in mycophenolate mofetil.Methods: The column was DB-624 capillary column,the carrier gas was nitrogen,the flow rate was 3.0 ml·min-1,and the detector was a hydrogen flame ionization detector. The initial temperature was 35℃,maintaining for 1 min,and rose to 90℃ at the rate of 5℃·min-1,and then rose to 150℃ at the rate of 15℃ ·min-1,finally rose to 225℃ at the rate of 25℃ ·min-1,and maintaining for9 min. The inlet temperature was 200℃,and the detector temperature was 250℃. The split ratio was 10 ∶1,and the injection volume was 1 μl. Results: The linear range was 0.060-6.06 mg·ml-1 for methanol (r = 0.999 2),0.100-10.06 mg·ml-1 for ethanol (r =0.999 0),0.099-9.96 mg·ml-1 for acetone (r = 0.998 9),0.012-1.256 mg·ml-1 for methylene chloride (r = 0.998 7),0.006-0.561 mg·ml-1 for n-hexane (r = 0.998 5),0.100-10.04 mg·ml-1 for ethyl acetate (r = 0.998 6),0.078-7.80 mg·ml-1 for cyclohexane (r =0.999 1),0.017-1.73 mg·ml-1 for toluene (r = 0.999 0),0.101-10.06 mg·ml-1 for butyl acetate (r = 0.999 5),0.018-1.83 mg·ml-1 for N,N-dimethylformamide (r = 0.998 5),and 0.044-4.42 mg·ml-1 for xylene (r = 0.998 3). The average recovery was 97.7% (RSD= 1.4%,n= 9),97.9% (RSD= 1.3%,n= 9),103.2% (RSD = 2.1%,n = 9),98.8% (RSD = 2.2%,n = 9),99.1% (RSD =2.2%,n = 9),100.4% (RSD = 4.5%,n = 9),98.5% (RSD = 2.4%,n = 9),99.6% (RSD = 3.3%,n = 9),98.9% (RSD = 2.7%,n =9),101.7% (RSD = 4.3%,n = 9) and 95.2% (RSD = 2.3%,n = 9),respectively. The lower limit of detection was 6.06,10.06,3.32,2.51,2.24,5.02,2.60,1.73,10.07,3.65 and 4.42 μg·ml-1,respectively. Conclusion: The method is simple,accurate,reliable and sensitive,and can be used for the determination of residual solvents in mycophenolate mofetil.
作者
李香荷
王强
郭毅
王柳
王韵
常俊山
Li Xianghe;Wang Qiang;Guo Yi;Wang Liu;Wang Yun;Chang Junshan(Hebei Institute for Drug Control,Shijiazhuang 050011,China)
出处
《中国药师》
CAS
2019年第3期478-481,共4页
China Pharmacist
