表阿霉素中有关物质的LC/ESI/MS分析  

Determination of Related Substances in Epirubicin by Using LC/ESI/MS

作　　者：王颖[1] 盛龙生[1] 张正行 安登魁 

机构地区：[1]中国药科大学分析测试中心,南京210009

出　　处：《药物分析杂志》2001年第6期392-395,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:检查并推证表阿霉素中的有关物质。方法:采用 LC/ESI/MS联用技术测定,在Agilent　1100 LC/MSD系统上完成,其中液相色谱条件为:柱ZorbaxSB4.6mm×75mm,3μm,柱温:35℃,流动相:A）0.5％乙酸;B）甲醇-乙腈（1:1）,含0.1％乙酸,线性梯度:0～25min,25％B～45％B。流速:1mL·min-1,柱后分流:1:1,检测:UV234nm。质谱条件:离子化方式ESI（+）,扫描范围200～1200m/z,干燥气流速10L·min-1,温度350℃,雾化气压2.07×105Pa,毛细管电压 4 000 V,碎裂器电压 70 V、150 V。结果:从表阿霉素中分离出多个有关物质,其中 4个有关物质经质谱解析推导分别为表阿霉素二聚体、柔红霉素以及2个表阿霉素的同系物。结论:表阿霉素在生产过程中可生成多种结构类似物或聚合物,LC/ESI/MS作为一种高效分离与灵敏检测相结合的现代分析方法,为快速有效地检查和鉴定药品生产过程中可能产生的有关物质提供了有力的技术保证。Objective: In order to identify and detect the related substances in epirubicin, an effective analysis method was developed. Method: By using LC/ESI/MS combination technology and operating at different fragmentor voltag, HPLC condition: column Zorbax SB 4.6 mm×75mm, 3Um, temp: 35℃ , mobile phase: A) 0.5% acetic acid; B) methanol - acetonitrile (1:1) containing 0.1% acetic acid, gradient: 0 -25 min 25 % B-45 % B, flow rate 1 mL ·min-1, postcolumn split ratio 1:1, detection: UV 234 nm. MS parameter: ESI ( + ), 200 - 1 200 m/z, drying gas flow 10 L·min-1, temp: 350℃, nebulizer pressure 2.07×105 Pa, Vcap 4 000 V, fragmentor voltage: 70 , 150 V. Results: Several substances were resolved with HPLC, and their structures were elucidated as epirubicin dimmer , daunorubicin and two analogs of epirubicin respectively according to their MS characteristics. Conclusion: During the epirubicin manufacture process, there were some related substances occurred; ESI as a 'soft' ionization mode, waseasily to get molecular ion of each compound and fragment ions with higher fragmentor voltage, so was the molecular structure elucidation.

关 键 词：表阿霉素 有关物质 液质联用 LC/ESI/MS 抗肿瘤抗生素 

分 类 号：R979.14[医药卫生—药品] R927.2[医药卫生—药学]