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目的采用LC-ESI-MS/MS法同时测定大鼠血浆中的吴茱萸碱、吴茱萸次碱和吴茱萸内酯,并研究这3种活性物质在大鼠体内的药动学特征。方法取100μL血浆样品,用甲基叔丁基醚-二氯甲烷(3∶1)萃取,选择右啡烷为内标。采用BDS Hypersil C18色谱柱(100 mm×2.1 mm,2.4μm),乙腈-2 mmol·L-1乙酸铵(含0.05%甲酸)(60∶40)为流动相,采用AB Sciex 4000 Q TRAP型三重四级杆串联质谱,ESI源,多反应监测(MRM)正离子模式。经检测,吴茱萸碱、吴茱萸次碱、吴茱萸内酯和内标的检测离子对分别为:m/z 304.3→134.4、m/z 288.1→273.3、m/z 471.3→425.2、m/z 258.0→201.0。结果血浆中吴茱萸碱、吴茱萸次碱和吴茱萸内酯的线性范围均为0.5~1×103ng·mL-1(r>0.9960),提取回收率均>70%,日内、日间RSD均<15%。大鼠口服吴茱萸提取物后,血浆中吴茱萸碱、吴茱萸次碱及吴茱萸内酯的Cmax分别为19.02±2.15、19.83±5.83、41.61±7.48 ng·L-1,Tmax分别为1.17±0.29、1.25±0.66、0.63±0.14 h,T1/2分别为4.64±2.14、5.72±1.34、4.25±1.72 h;绝对生物利用度分别为16.96%±2.80%、12.02%±3.17%、5.43%±1.99%。结论所用方法准确、快速、灵敏,并成功用于临床前的药动学研究。
OBJECTIVE To simultaneously determine evodiamine, rutaecarpine and evodiamine in rat plasma by LC-ESI-MS / MS and study the pharmacokinetics of these three active substances in rats. Methods 100 μL plasma samples were extracted with methyl tert-butyl ether-methylene chloride (3: 1) and dextrorphan was selected as internal standard. The mobile phase consisted of BDS Hypersil C18 column (100 mm × 2.1 mm, 2.4 μm), acetonitrile-2 mmol·L -1 ammonium acetate (0.05% formic acid) (60:40) and AB Sciex 4000 Q TRAP triple Quadrupole rod tandem mass spectrometry, ESI source, multiple reaction monitoring (MRM) positive mode. The detected ion pairs of evodiamine, rutaecarpine, evodiamine and the internal standard were respectively detected as follows: m / z 304.3 → 134.4, m / z 288.1 → 273.3, m / z 471.3 → 425.2, and m / z 258.0 → 201.0. Results The linear ranges of evodiamine, rutaecarpine and evodiamine were 0.5-1 × 103 ng · mL-1 (r> 0.9960) in plasma. The average recoveries were both 70% . After oral administration of Evodia rutaecarpa extract, the Cmax values of evodiamine, rutaecarpine and evodiamine in plasma were 19.02 ± 2.15, 19.83 ± 5.83 and 41.61 ± 7.48 ng · L-1, respectively, and the Tmax were 1.17 ± 0.29 and 1.25 ± 0.66,0.63 ± 0.14 h, T1 / 2 were 4.64 ± 2.14, 5.72 ± 1.34 and 4.25 ± 1.72 h, respectively. The absolute bioavailability were 16.96% ± 2.80%, 12.02% ± 3.17% and 5.43% ± 1.99% respectively. Conclusion The method used is accurate, rapid and sensitive and has been successfully used in pre-clinical pharmacokinetic studies.