栀子大黄汤配伍变化对枳实中总柚皮素和总橙皮素药动学的影响

Effect of different compatibility of Zhizi Dahuang decoction on pharmacokinetics of naringenin and hesperetin

采用HPLC-UV测定枳实和栀子大黄汤灌胃后大鼠血浆中总柚皮素和总橙皮素浓度,血浆样品通过液液萃取法进行提取,通过酸水解的方式将柚皮素、橙皮素缀合物转化为游离柚皮素、橙皮素。Phecda C18色谱柱(4.6 mm×150 mm,5μm),流动相0.1%磷酸-甲醇,梯度洗脱,流速1.0 mL·min-1。采用DAS 2.0数据处理软件及SPSS 16.0统计软件分别进行药动学参数计算及比较。枳实组(ZS)和栀子大黄汤组(ZZDHD)中总柚皮素、总橙皮素的药动学参数存在显著性差异,ZS组中总柚皮素的Cmax,AUC0-t分别比ZZDHD组的高出73.5%,65.9%,ZS组中总橙皮素的Cmax,AUC0-t分别比ZZDHD组的高出63.5%,119.1%。说明栀子大黄汤中其余成分对枳实中总柚皮素、总橙皮素的药动学特征具有显著影响,经配伍后其Cmax,AUC0-t显著降低。该方法简便准确、灵敏度高、特异性好,可以应用于血浆中总柚皮素和总橙皮素含量测定。

An HPLC-UV method was developed for the determination of total naringenin and total hesperetin in rat plasma after oral administration of Citrus aurantium Immaturus extracts and Zhizi Dahuang decoction. Plasma samples were pretreated with liquid- liquid extraction procedure and acid hydrolysis method was used for converting conjugated naringenin and hesperetin to their respective free forms. Plasma samples were separated on a C18 column（4. 6 mm × 150 mm,5 μm）, using 0. 1% phosphoric acid and methanol as mobile phase at a flow rate of 1.0 mL· min -1 with gradient elution. DAS 2. 0 software was applied to calculate the pharmacokinetic pa- rameters while the SPSS 16.0 software was used for statistical analysis. Significant differences were observed, the Cmax, AUC0-t, of total naringenin in ZS group was 73.5% and 65.9% higher than those in ZZDHD group, respectively; the Cmax, AUC0-t, of total hesperetin in ZS group was 63.5% and 119. 1% higher than those in ZZDHD group, respectively. There is a obvious decrease in Cmax, and AUCo., of total naringenin and total hesperetin after compatibility and their pharmacokinetic characteristics changed greatly due to the combina- tion of other herbs. The estabhshed method was rapid, sensitive, selective and accurate, and it could be applied in the determination of total naringenin and total hesperetin in rat plasma.