| Part one The study on quality control of Shaoyao-Gancao-TangObjective:To develop an ultra performance liquid chromatography (UPLC) method was for simultaneous determination of gallic acid, albiflorin, peoniflorin, glycyrrhizin, benzoic acid, liquiritigenin, isoliquiritigenin and formononetin in Shaoyao-Gancao-Tang (SGT), and applied for quality control.Methods:The chromatographic separation was performed on an Acquity BEH C18 column (100 X 2.1 mm i. d.,1.7μm). The mobile phase was a mixture of 0.5% aqueous acetic acid and acetonitrile employing gradient elution at the flow rate of 0.3 mL/min. The UPLC method was validated by calibration curves, sensitivity, precision, recovery, stability. And then the contents of gallic acid, albiflorin, peoniflorin, glycyrrhizin, benzoic acid, liquiritigenin, isoliquiritigenin and formononetin in SGT were quantitative analysed.Results:1. All calibration curves showed good linearity (R2≥0.9996) over the tested ranges. The limits of detection and quantification were 3.992 and 13.31 ng/ml, respectively. The RSDs for intra-and inter-day were within 4.8% at three levels, and the recoveries were 96.22-102.2% with RSDs≤3.6%. The eight compounds were stable within 48h at 4℃and 25℃(RSDs≤4.7%).2. The contents of gallic acid, albiflorin, peoniflorin, glycyrrhizin, benzoic acid, liquiritigenin, isoliquiritigenin and formononetin in SGT were 42.02±0.47、52.61±1.30.103.5±1.16.41.66±0.89、12.95±0.43、8.715±0.13、2.298±0.032、0.4513±0.0090 mg/L.Conclusion:The UPLC method was suitable for applying to the quality assessment of SGT. Part two Pharmacokinetic comparisons of albiflorin and paeoniflorin after oral administration of Shaoyao-Gancao-Tang and single herb Paeony decoction to ratsObjective:To compare the pharmacokinetics of albiflorin and paeoniflorin in rats following oral administration of Shaoyao-Gancao-Tang and single herb Paeony decoction.Methods:Male Sprague-Dawley rats (250-280g) were randomized into 2 groups:SGT group (n=6) and single herb Paeony decoction group (n=6). The 2 groups were administered an oral dose of SGT or single herb Paeony decoction. Blood samples were collected at different time points and prepared with methanol. The contents of albiflorin, peoniflorin in SGT and single herb Paeony decoction were quantitatively analyzed by UPLC developed in part one. Plasma concentrations of albiflorin and paeoniflorin were determined using a UPLC method, and main pharmacokinetic parameters were evaluated.Results:1. The UPLC method has advantages of rapid, satisfactory selectivity, accuracy, precision, recovery, stability.2. There were statistically significant differences in the pharmacokinetic parameters of albiflorin and paeoniflorin including the values for Cmax, AUC0-t, AUC0-∞, V/F and CL/F between the two groups.3. The contents of albiflorin and paeoniflorin of SGT were lower than single herb Paeony decoction.4. The total systemic exposure level of these two compounds was lower in the SGT group than that in single herb Paeony decoction group.Conclusions:1. Pharmacokinetic parameters of albiflorin and paeoniflorin were significantly altered when Radix Paeoniae Alba was used with Radix Glycyrrhizae.2. The total systemic exposure level of albiflorin and paeoniflorin was lower in the SGT group than that in single herb Paeony decoction group. Part three Effects of Shaoyao-Gancao-Tang on the Pharmacokinetics of Intravenous Paclitaxel in RatsObjective:To investigate the effect of Shaoyao-Gancao-Tang on the pharmacokinetics of intravenously administered paclitaxel in rats.Methods:Male Sprague-Dawley rats (270-300g) were randomized into 3 groups (n=6 for each treatment):Two groups of rats received an oral dose of SGT for 14 consecutive days (long-term pretreatment) or 1 day (short-term pretreatment), and the third group received distilled water, as a control. Blood samples were collected at different time points after intravenous administration of paclitaxel and prepared with ethyl acetate. Plasma concentrations of paclitaxel were determined using a UPLC method, and main pharmacokinetic parameters were evaluated.Results:1. The UPLC method has advantages of rapid, satisfactory selectivity, accuracy, precision, recovery, stability.2. There were statistically significant differences in the pharmacokinetic parameters of paclitaxel including the values for AUCo-t, AUC0-∞Vdss and CL between long-term pretreatment with SGT group and control group. There were significant decreases in area under the curve (p< 0.01) and the total clearance increased by 1.2 fold (p< 0.01) in the long-term pretreatment of SGT.3. The pharmacokinetic parameters of paclitaxel were not significantly affected by short-term pretreatment with SGT.4. The total systemic exposure level of these two compounds was lower in the SGT group than that in single herb Paeony decoction group. Conclusions:1. Pharmacokinetic parameters of paclitaxel were significantly altered with oral dose of SGT for 14 consecutive days (long-term pretreatment).2. The pharmacokinetic parameters of paclitaxel were not significantly affected by oral dose of SGT for 1 day (short-term pretreatment). |
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