盐酸昂丹司琼7种微量杂质的鉴定及定量分析
目的 建立HPLC/DAD/MS法同时测定盐酸昂丹司琼合成中可能存在的主要7种微量杂质.方法 采用高效液相色谱法,色谱柱:Allsphere Cyano(CN)柱,4.6mm×250mm,5μm;流动相:乙腈-0.02 mol·L-1醋酸铵水溶液梯度洗脱,梯度洗脱条件如下:0 min,18:82;10 min,19:81;12 min,60:40;32 min,60:40;32.1 min,18:82;40 min,18:82;柱温:30℃;流速:0.8mL·min-1;进样量:10μL;检测波长:266 nm.HPLC/DAD/MS条件离子源:APCI;扫描模式:正离子.结果 盐酸昂丹司琼及其7种杂质9-甲基-3-(二甲胺基)甲基-1,2,3,9-四氢-4H-咔唑-4-酮(4H-carbazol-4-one,3-[(dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-,A1)、9-甲基-3-(二甲胺基)甲基-1,2,3,9-四氢-4H-咔唑-4-酮(4H-carbazol-4-one,3-[(dimethylamino)methyl)-1,2,3,9-tetrahydro-,A2)、1,2,3,9-四氢-9-甲基-4H-咔唑酮(4H-carbazol-4-one,1,2,3,9-tetrahydro-9-methyl-,A3),1,2,3,9-四氢-4H-咔唑酮(4H-carbazol-4-one,1,2,3,9-tetrahydro-,A4)、1,2,3,9-四氢-9-甲基-3-亚甲咔唑酮(4H-carbazol-4-one,1,2,3,9-tetrahydro-9-methyl-3-methylene-,A5),1,2,3,9-四氢-3-(1H-咪唑基-1-甲基)-9-甲基-4H-咔唑酮(4H-carbazol-4-one,1,2,3,9-tetrahydro-3-[(1H-imidazol-l-yl)methyl]-9-methyl-,Z1),1,2,3,9-四氢-3-[(2-甲基-1H一咪唑-1-)-4H-咔唑酮(4H-carbazol-4-one,1,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-l-yl)methyl]-,Z2)的线性范围分别为:0.009 7-1.94μg(r=0.9997),0.0104-2.08μg(r=0.9997),0.0098-1.96μg(r=0.9999),0.0095-1.90μg(r=0.9998),0.0105-2.10 μg(r=0.9998),0.0096-1.92μg(r=0.9998),0.0104-2.08μg(r=0.9998),0.0105-2.10μg(r=0.9997);最低检测限分别为0.29,0.31,0.49,0.10,0.10,0.29,0.31,0.16 ng;定量限分别为0.97,1.04,1.47,0.29,0.32,0.96,1.04,0.52 ng.结论 盐酸昂丹司琼及其7种微量杂质分离良好;对其两批制剂及一批原料药进行检测,其中原料药中检出杂质A1,A3,A5含量超过0.11%.该方法简单、准确、可靠、具有较广泛的适用性,可以作为盐酸昂丹司琼及其7种可能的微量杂质的质量控制方法.
盐酸昂丹司琼、高效液相色谱-二极管阵列-质谱联用、徽量杂质检测
46
R917(药物基础科学)
国家科技重大专项;国家科技支撑计划
2012-01-07（万方平台首次上网日期，不代表论文的发表时间）
1436-1440
