| 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。 |
| 关键词: 五味子 木脂素类 代谢速率 代谢产物 |
| DOI：10.3724/SP.J.1008.2014.00426 |
| 投稿时间：2013-09-09修订日期：2013-12-30 |
| 基金项目:国家自然科学基金青年科学基金（81303192）. |
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| Metabolic rates and metabolites of three lignans in Schisandra chinensis (Turcz.) Baill in rat liver microsomes |
| ZHANG Hai1,2,ZHOU Yan-ni1,SUN Sen1,SUN Feng-feng1,CHAI Yi-feng2,ZHANG Guo-qing1* |
(1. Department of Pharmacy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China;
2. Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
*Corresponding author.) |
| Abstract: |
| 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 (6040 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. |
| Key words: Schisandra chinensis (Turcz.) Baill lignans metabolic rate metabolites |
