栀子柏皮汤在正常和肝损伤模型大鼠体内药动学比较研究  

Pharmacokinetic comparison of Zhizi Baipi Decoction in normal and liver injury model rats

作　　者：邸馥郁 王鑫[1] 刘有平[1] 邸欣[1] DI Fuyu;WANG Xin;LIU Youping;DI Xin(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2021年第4期373-378,共6页Journal of Shenyang Pharmaceutical University

摘　　要：目的比较栀子柏皮汤中5个活性成分在正常和肝损伤模型大鼠体内的药动学差异,为该复方的临床应用提供参考。方法 12只健康雄性SD大鼠随机分为正常组和肝损伤模型组,灌胃给予栀子柏皮汤(13 g·mL-1,按生药量计),采用LC-MS/MS法测定给药后不同时刻大鼠血浆中京尼平苷、小檗碱、延胡索乙素、巴马汀和甘草素的浓度。以葛根素为内标,血浆样品经乙腈(含体积分数0.1%甲酸)沉淀蛋白处理,采用Thermo Syncronis C18柱(100 mm×2.1 mm, 5μm)分离,以乙腈-2 mmol·L-1乙酸铵(含体积分数0.1%甲酸)(体积比30∶70)为流动相;质谱检测采用ESI源正离子化方式,以选择反应监测(SRM)模式进行扫描定量。用DAS 2.1.1软件按非房室模型计算主要药动学参数,并比较5个活性成分的药动学参数在正常组和模型组之间是否有统计学差异。结果与正常组比较,模型组大鼠体内除小檗碱外的其他4个活性成分的ρmax、AUC0-t和AUC0-∞均显著增加,tmax和t1/2显著延长。除ρmax和t1/2外,小檗碱其他参数呈现出与另外4种活性成分相同的变化趋势。小檗碱的ρmax和t1/2在模型组中表现的变化趋势与其他化合物稍有差异,并且统计学检验结果显示这两项指标在正常组和模型组之间不存在统计学差异。结论肝损伤状态对栀子柏皮汤中活性成分的体内过程有一定影响。Objective To compare pharmacokinetics of active constituents from Zhizi Baipi Decoction in normal and liver injury conditions and provide references for the application in clinical.Methods Rats were randomly divided into the normal group and the model group with 6 rats in each group.Rats were orally given Zhizi Baipi Decoction at a dose of 0.3 g·mL-1,plasma samples were collected from the fosse orbital at different time point.The LC-MS/MS was adopted for the simultaneous determination of five active compounds.The analytes, together with the internal standard(puerarin),were extracted from rat plasma by precipitate protein method with acetonitrile(0.1% formic acid).The analytes were performed on a Thermo Syncronis C18 column(100 mm×2.1 mm, 5 μm) with the mobile phase composed of acetonitrile-water(0.1% formic acid and 2 mmol·L-1 ammonium acetate) with isocratic elution(V∶V=30∶70).Mass spectrometric detection was achieved by mass spectrometer equipped with an electrospray source interface operating in positive ionization mode.According to the non-compartmental model, the main pharmacokinetic parameters were calculated by DAS 2.1.1 software and the pharmacokinetic parameters of the five active ingredients were compared between the normal group and the model group.Results Compared with the normal group, ρmax,AUC0-t and AUC0-∞ of the other four active ingredients were significantly increased for the four analytes(except berberine) in the model group, while tmax and t1/2 were significantly extended.In addition to ρmax and t1/2,other parameters of berberine showed the same trend as the other four active ingredients.The trends of ρmax and t1/2 of berberine in the model group were slightly different from those of other compounds.The statistical tests showed that there was no statistical difference between the two groups in the normal group and the model group.Conclusion The state of liver injury has an effect on the process in vivo of the active ingredients in Zhizi Baipi Decoction.

关 键 词：栀子柏皮汤 肝损伤 药动学 血浆 LC-MS/MS 

分 类 号：R917[医药卫生—药物分析学]