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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 HPLC / DAD / MS method for simultaneous determination of ondansetron hydrochloride and its three trace impurities, namely, 1,2,3,4-tetrahydro-9-methyl-4H-carbazolone , 9-methyl-3- (dimethylamino) methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one hydrochloride (intermediate II), 1,2,3 , 9-tetrahydro-9-methyl-3-methylenecarbazolone (Impurity III). METHODS: Allsphere Cyano (CN) column (250 mm × 4.6 mm, 5 μm) was used as the mobile phase. The mobile phase was acetonitrile-0.02 mol·L-1 sodium phosphate monobasic solution Sodium hydroxide adjusted to pH 5.4) with gradient conditions as follows: 0.01 min, 25:75; 10.0 min, 75:25; 15.0 min, 75:25; 15.10 min, 25:75; 20.0 min, 25:75 ; Flow rate: 1mL · min-1; column temperature: 25 ℃; injection volume: 10μL, detection wavelength 248nm, ion source: ESI, scanning mode positive ions. Results: The linear ranges of ondansetron hydrochloride, intermediate Ⅰ, intermediate Ⅱ and impurity Ⅲ were 0.01-2.53μg (r = 0.9999), 0.01-2.52μg (r = 0.9999), 0.01-2.53μg = 0.9999) and 0.01 ~ 2.48μg (r = 0.9999) respectively. The minimum detection limits were 0.125,0.125,0.25,0.125ng, respectively. The limits of quantification were 0.375,0.375,0.75,0.375ng respectively. CONCLUSION: Ondansetron hydrochloride and its three trace impurities are well separated. The impurity Ⅲ is detected in the crude drug, and the content is 0.10%. The method is simple, accurate, reliable and reproducible. It can be used as a quality control method for ondansetron hydrochloride and its three possible trace impurities.