三妙丸与四妙丸中6种生物碱在大鼠体内的药动学和肠道吸收差异研究

Comparative analysis of pharmacokinetics and intestinal absorption of six alkaloids between Sanmiao Pills and Simiao Pills in rats

该文研究三妙丸与四妙丸中6种生物碱类成分在大鼠体内的药动学和肠道吸收差异,探讨两药的功效差异。大鼠灌胃三妙丸和四妙丸后于不同时间点采血,样品处理后,UPLC-MS/MS检测6种生物碱在血浆中的含量,ACE Excel 3 C_(18)色谱柱,流动相为0.1%甲酸水溶液-乙腈,梯度洗脱分析物,正离子模式检测,计算成分血药浓度和药动学参数。在体单向肠灌流研究生物碱的肠道吸收,计算肠道吸收参数。结果建立了同时检测血浆中6种生物碱UPLC-MS/MS分析方法,该方法专属性、线性、精密度、准确度、回收率、基质效应和稳定性良好。药动学研究发现相比于三妙丸,四妙丸中黄柏碱、小檗碱、木兰花碱、小檗红碱、药根碱的C_(max)和AUC显著增加,CL/F降低,提示其血药水平提高。四妙丸中黄柏碱、小檗碱和木兰花碱的肠道吸收参数K_(a)和P_(eff)显著高于三妙丸。四妙丸中生物碱成分的肠道吸收和血药浓度水平显著高于三妙丸,提示前者组方更有利于生物碱成分入血发挥抗炎和降尿酸的作用。

The present study investigated the differences in pharmacokinetics and intestinal absorption of six alkaloids in Sanmiao Pills and Simiao Pills in rats and explored the different efficacies of the two formulae.After oral administration of Sanmiao Pills and Simiao Pills in rats,blood samples were collected at different time points.Samples were prepared for the determination of six alkaloids in plasma by UPLC-MS/MS.The chromatography was performed on an ACE Excel 3 C_(18) column with acetonitrile-0.1%formic acid in water as the mobile phase for gradient elution.Analytes were detected in the positive ion mode.Plasma concentrations and pharmacokinetic parameters were calculated.Intestinal absorption of alkaloids was investigated by single-pass intestinal perfusion and absorption parameters of ingredients were calculated.The results showed that the UPLC-MS/MS method for simultaneous determination of concentrations of six alkaloids in plasma was developed and validated by methodological investigations,such as specificity,calibration curves,precision,accuracy,recovery,matrix effect,and stability.The results of the pharmacokinetic assay revealed that C_(max) and AUC values of phellodendrine,berberine,magnoflorine,berberrubine,and jatrorrhizine in Simiao Pills were significantly increased,and CL/F values were reduced as compared with those in Sanmiao Pills,which indicated the increase in plasma concentrations of alkaloids.The intestinal absorption parameters K_(a) and P_(eff) values of phellodendrine,berberine,and jatrorrhizine in Simiao Pills were higher than those in Sanmiao Pills.The intestinal absorption and plasma concentrations of alkaloids in Simiao Pills were significantly higher than those in Sanmiao Pills,suggesting that the composition of Simiao Pills was more conducive to the alkaloids into the blood to resist inflammation and lower uric acid.