HPLC/DAD/MS法测定盐酸昂丹司琼及其3种微量杂质  

HPLC/DAD/MS determination of Ondansetron Hydrochloride and its three impurities

作　　者：冯茹[1,2] 费绍芳[1] 杨蓓蓓[1] 吴松[1] 关铭[2] 王琰[1] 王慕邹[1] 

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京100050 [2]吉林大学药学院,长春130021

出　　处：《药物分析杂志》2010年第3期499-503,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：国家科技支撑计划课题(2008BA155B00)

摘　　要：目的:建立HPLC/DAD/MS法同时测定盐酸昂丹司琼及其3种微量杂质,即1,2,3,4-四氢-9-甲基-4H-咔唑酮(中间体Ⅰ)、9-甲基-3-(二甲胺基)甲基-1,2,3,9-四氢-4H-咔唑-4-酮盐酸盐(中间体Ⅱ)、1,2,3,9-四氢-9-甲基-3-亚甲咔唑酮(杂质Ⅲ)。方法:采用高效液相色谱法,色谱柱:Allsphere Cyano(CN)柱(250mm×4.6mm,5μm);流动相:乙腈-0.02mol·L-1磷酸二氢钠水溶液(用1mol·L-1氢氧化钠调节pH5.4)梯度洗脱,梯度条件如下:0.01min,25∶75;10.0min,75∶25;15.0min,75∶25;15.10min,25∶75;20.0min,25∶75;流速:1mL·min-1;柱温:25℃;进样量:10μL,检测波长248nm,离子源:ESI,扫描模式正离子。结果:盐酸昂丹司琼、中间体Ⅰ、中间体Ⅱ、杂质Ⅲ的线性范围分别为:0.01～2.53μg(r=0.9999),0.01～2.52μg(r=0.9999),0.01～2.53μg(r=0.9999),0.01～2.48μg(r=0.9999);最低检测限分别为0.125,0.125,0.25,0.125ng;定量限分别0.375,0.375,0.75,0.375ng。结论:盐酸昂丹司琼及其3种微量杂质分离良好;其原料药中检出杂质Ⅲ,含量为0.10%。该方法简单、准确、可靠、重现性好,可以作为盐酸昂丹司琼及其3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 three impurities, 1, 2, 3, 4-tetrahydro-9-methylcarbazol-4-one （Intermediate I）, 1, 2, 3, 9-tetrahydro-9-methyl-3-[（2-methylamino） methyl]-4H-carbazol-4-one hydrochloride （intermediate Ⅱ）, and 1, 2, 3, 9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one （Impurity Ⅲ）. Methods： The analysis was achieved on an Allsphere Cyano （CN） column （250 mm×4.6 mm,5 μm） using a mobile phase of acetonitrile-0.02 mol·L-1 sodium dihydrogen phosphate solution （previously adjusted with 1 mol·L-1 sodium hydroxide to a pH of 5.4）in a total run time of 20 min （0.01 min, 25∶75; 10.0 min, 75∶25; 15.0 min, 75∶25; 15.1 min, 25∶75; 20.0 min, 25∶75） at a flow rate of 1 mL min-1 and a diode array detector was set at 248 nm. An ESI source was used with a positive ionization mode.Results： Ondansetron Hydrochloride and its three impurities were determined by the provided method. Ondansetron Hydrochloride, Intermediate I, Intermediate Ⅱ, and Impurity Ⅲ were linear over the range of 0.01-2.53 μg （r=0.9999）, 0.01-2.52 μg （r=0.9999）, 0.01-2.53 μg （r=0.9999）, 0.01-2.48 μg （r=0.9999）;The values of limit of detection （LOD） were 0.125, 0.125, 0.25, 0.125 ng, respectively, and values of limit of quantitation （LOQ） were 0.375, 0.375, 0.75, 0.375 ng, respectively. Conclusion： Ondansetron Hydrochloride and its impurities can be separated with a good resolution. Impurity Ⅲ was detected in the product of ondansetron hydrochloride 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.

关 键 词：盐酸昂丹司琼 HPLC/DAD/MS 微量杂质检查 

分 类 号：R917[医药卫生—药物分析学]