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HPLC-TOF/MS分析五味子中3个木脂素类成分在大鼠肝微粒体中的代谢速率及代谢产物
  • ISSN号:0258-879X
  • 期刊名称:《第二军医大学学报》
  • 时间:0
  • 分类:R285.5[医药卫生—中药学;医药卫生—中医学]
  • 作者机构:[1]第二军医大学东方肝胆外科医院药材科, 上海 200438, [2]第二军医大学药学院药物分析学教研室, 上海 200433
  • 相关基金:国家自然科学基金青年科学基金(81303192).
中文摘要:

目的 研究五味子中3个木脂素类成分五味子甲素、五味子醇乙、五味子酯甲在肝微粒体内的代谢速率,鉴别这3个木脂素类成分在肝微粒体中的代谢产物。方法 体外培养大鼠肝微粒体代谢模型,采用HPLC-MS法测定3个木脂素类成分的含量,并计算代谢速率。液相条件采用Agilent Zorbax SB-C18色谱柱(3.0 mm×100 mm,3.5 μm),60%的乙腈和40%的水等度洗脱,进样量5 μL,流速0.8 mL/min,柱温30℃,运行时间30 min。质谱ESI离子源选择离子监测,正离子模式,干燥气温度350℃,毛细管电压4 000 V,干燥气流速9.0 L/min,裂解气电压90 eV。采用HPLC-TOF/MS分析鉴别木脂素类成分的代谢产物,质谱参数与HPLC-MS的参数相同。结果 五味子甲素、五味子醇乙、五味子酯甲在0.010 22~2.044、0.044 24~2.212、0.042 32~2.116 μg/mL的线性范围内,线性关系良好(r〉0.999 0);方法学考察结果表明,日内、日间精密度RSD%均〈5%,基质效应〉75%,提取回收率〉80%。3个木脂素类成分在大鼠肝微粒体中代谢的半衰期分别为:五味子甲素0.721 0 min,五味子醇乙43.58 min,五味子酯甲86.63 min,采用HPLC-TOF/MS分析鉴别出五味子甲素的7个代谢产物、五味子醇乙的6个代谢产物、五味子酯甲的4个代谢产物。结论 五味子木脂素类成分在肝微粒体中易发生代谢,这将影响木脂素类成分的生物利用度及药效。

英文摘要:

Objective To investigate the metabolic rates of three lignans (deoxyschizandrin, schizandrol B and schisantherin) of Schisandra chinensis (Turcz.) Baill in rat liver microsomes, and to identify their metabolites. Methods Using the in vitro rat liver microsomal model, the contents of the 3 lignans were determined by HPLC-MS and the matobilic rates were calculated. The analytical conditions were as follows: column, Agilent Zorbax SB-C18 (3.0 mm×100 mm, 3.5 μm); mobile phase, acetonitrile/water (6040 V/V), with isocratic elution; injection volume, 5 μL; flowing rate, 0.8 mL/min; temperature of column, 30℃; running time, 30 min; selective ion monitoring (SIM) in positive ion mode was used in mass spectrometry, with the drying gas temperature being 350℃, capillary voltage being 4 000 V, drying gas flowing rate being 9.0 L/min, and fragmentor voltage being 90 eV. Their metabolites were identified by HPLC-TOF/MS, whose mass parameters were the same as those of HPLC-MS. Results Deoxyschizandrin, schizandrol B and schisantherin were separated with good linearity (r〉0.999 0) between 0.010 22-2.044, 0.044 24-2.212 and 0.042 32-2.116 μg/mL, respectively. The intra-day and inter-day precisions were less than 5%, the matrix effect was higher than 75%, and the extraction recovery rate was higehr than 80%. The metabolic half-life values of the 3 lignans were as follows: deoxyschizandrin 0.721 0 min,schizandrol B 43.58 min,and schisantherin 86.63 min. HPLC-TOF/MS identified 7 metabolites in deoxyschizandrin, 6 in schizandrol B and 4 in schisantherin. Conclusion The lignans in Schisandra chinensis (Turcz.) Baill are easy to be metabolized in rat liver microsomes, which will affect the bioavailability and pharmaceutical efficacy of lignans in Schisandra chinensis (Turcz.) Baill.

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期刊信息
  • 《第二军医大学学报》
  • 北大核心期刊(2011版)
  • 主管单位:第二军医大学
  • 主办单位:第二军医大学
  • 主编:吴孟超
  • 地址:上海市翔殷路800号
  • 邮编:200433
  • 邮箱:bxue@smmu.edu.cn
  • 电话:021-81870791
  • 国际标准刊号:ISSN:0258-879X
  • 国内统一刊号:ISSN:31-1001/R
  • 邮发代号:4-373
  • 获奖情况:
  • 2008年被评为首批"中国精品科技期刊"2008年获第二...,2004年获第四届全军医学期刊质量评比优秀奖,2002年获第二届国家期刊奖百种重点期刊奖,2000年获首届《CAJ-CD规范》执行评优活动执行优秀奖,1999年获上海高校优秀自然科学学报评比一等奖,1999年获全国高校自然科学学报及教育部优秀科技期...,1997年获上海科技期刊评比二等奖
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),英国农业与生物科学研究中心文摘,波兰哥白尼索引,荷兰文摘与引文数据库,荷兰医学文摘,美国剑桥科学文摘,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:30859