摘要
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,4.6 mm×250 mm,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-1-yl)methyl]-9-methyl-,Z1),1,2,3,9-四氢-3-[(2-甲基-1H-咪唑-1-)-4H-咔唑酮(4H-carbazol-4-one,1,2,3,9-tetrahydro-3-[(2-methyl-1H-imidazol-1-yl)methyl]-,Z2)的线性范围分别为:0.009 7～1.94μg(r=0.999 7),0.010 4～2.08μg(r=0.999 7),0.009 8～1.96μg(r=0.999 9),0.009 5～1.90μg(r=0.999 8),0.010 5～2.10μg(r=0.999 8),0.009 6～1.92μg(r=0.999 8),0.010 4～2.08μg(r=0.999 8),0.010 5～2.10μg(r=0.999 7);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。
OBJECTIVE To establish a high performance liquid chromatography-diode array detection-mass spectrometry（HPLC/DAD/MS） method to simultaneously determine ondansetron hydrochloride and its seven impurities,which are common in the synthesis of ondansetron hydrochloride.METHODS The analysis was performed on an Allsphere Cyano（CN） column（4.6 mm×250 mm,5 μm） using a mobile phase of acetonitrile-0.02 mol·L-1 ammonium acetate solution in a total run time of 40 min（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） at a flow rate of 0.8 mL·min-1,and the diode array detector was set at 266 nm.The column temperature was maitained at 30 ℃.An APCI source was used with a positive ionization mode.RESULTS Ondansetron hydrochloride and its seven impurities were linear over the range of 0.009 7-1.94 μg（r=0.999 7）,0.010 4-2.08 μg（r=0.999 7）,0.009 8-1.96 μg（r=0.999 9）,0.009 5-1.90 μg（r=0.999 8）,0.010 5-2.10 μg（r=0.999 8）,0.009 6-1.92 μg（r=0.999 8）,0.010 4-2.08 μg（r=0.999 8）,0.010 5-2.10 μg（r=0.999 7）.The detection limits（LOD） were 0.29,0.31,0.49,0.10,0.10,0.29,0.31 and 0.16 ng,respectively,and the quantitation limits（LOQ） were 0.97,1.04,1.47,0.29,0.32,0.96,1.04 and 0.52 ng,respectively.CONCLUSION Ondansetron hydrochloride and its impurities can be separated with a good resolution.Impurities A1,A3,A5 were detected in ondansetron hydrochloride raw material with a content of 0.10%.The method is simple,accurate,reliable,and reproducible,and it can be applied to control the quality of ondansetron hydrochloride.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2011年第18期1436-1440,共5页
Chinese Pharmaceutical Journal
基金
国家科技重大专项综合平台(2009ZX09301-003-5-1和2009ZX09301-003-7-1)
国家科技支撑计划课题(2008BA155B00)
