Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison
Abstract
:1. Introduction
2. Results and Discussion
2.1. Method Development
2.2. Method Validation
2.2.1. Specificity and Linearity
2.2.2. Precision and Accuracy
2.2.3. Recovery and Matrix Effect
2.2.4. Stability
2.3. Pharmacokinetic Interactions
2.3.1. AF or Other Ingredients in TPG Enhanced Exposure and Reduced Elimination of PF in Rats
2.3.2. Other Ingredients in TPG Reduced Elimination of AF in Rats
2.4. Pharmacokinetics Comparisonunder Normoxic and Hypoxic Conditions
3. Experimental Section
3.1. Materials and Reagents
3.2. Animals
3.3. UPLC-MS/MS Instruments and Conditions
3.4. Preparation of Standard Stock Solutions and Quality Control Samples
3.5. Plasma Sample Preparation
3.6. UPLC-MS/MS Method Validation
3.6.1. Specificity, Linearity and LLOQ
3.6.2. Accuracy and Precision
3.6.3. Extraction Recovery and Matrix Effect
3.6.4. Stability
3.7. in vivo Pharmacokinetic Experiment
3.8. Data Processing and Comparison
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Compounds | Added (ng/mL) | Intra-Day (n = 5) | Inter-Day (n = 15) | ||
---|---|---|---|---|---|
Accuracy (%) | Precision (RSD%) | Accuracy (%) | Precision (RSD%) | ||
AF | 1.0 | 96.9 | 13.0 | 108.4 | 14.6 |
100 | 97.3 | 1.7 | 99.8 | 6.7 | |
1000 | 105.9 | 1.3 | 95.8 | 9.3 | |
PF | 1.0 | 98.8 | 12.3 | 97.8 | 14.2 |
100 | 108.2 | 5.3 | 111.3 | 5.2 | |
1000 | 105.4 | 6.6 | 104.8 | 5.2 |
Parameters (Unit) | PF Alone | PF Combined with AF | PF in TPG |
---|---|---|---|
AUC(0→24 h) (ng/mL·min ) | 35,702 ± 6355.8 | 51,907 ± 13,552 * | 54,128 ± 18,416 * |
MRT(0→24 h) (min) | 109.6 ± 25.3 | 199.9 ± 97.4 ** | 288.8 ± 44.7 *** |
t1/2 (min) | 108.6 ± 37.8 | 97.9 ± 39.9 | 234.6 ± 96.2 ** |
tmax (min) | 35.0 ± 12.2 | 41.7 ± 39.2 | 23.3 ± 10.3 |
Cmax (ng/mL) | 332.7 ± 63.6 | 319.8 ± 120.9 | 290.9 ± 141.1 |
CL (L·kg/min) | 2.3 ± 0.4 | 1.6 ± 0.4 | 1.7 ± 0.6 |
Parameters (Unit) | AF Alone | AF Combined with PF | AF in TPG |
---|---|---|---|
AUC(0→24 h) (ng/mL·min) | 8527.2 ± 2194.3 | 7754.7 ± 1897.5 | 11,777 ± 3419.4 |
MRT(0→24 h) (min) | 135.0 ± 29.3 | 178.2 ± 93.2 | 225.8 ± 32.1 * |
t1/2 (min) | 119.6 ± 29.7 | 130.1 ± 58.7 | 215.7 ± 91.9 * |
tmax (min) | 26.7 ± 8.2 | 41.7 ± 39.2 | 31.7 ± 16.0 |
Cmax (ng/mL) | 70.3 ± 19.1 | 42.4 ± 18.7 ** | 56.9 ± 12.9 |
CL (L·kg/min) | 1.7 ± 0.5 | 1.8 ± 0.6 | 1.2 ± 0.4 |
Parameters (Unit) | PF under Normoxia | PF under Hypoxia |
---|---|---|
AUC(0→24 h) (ng/mL·min) | 35,702± 6355 | 26,600 ± 4729 * |
MRT(0→24 h) (min) | 109.6 ± 25.3 | 127.2 ± 35.3 |
t1/2 (min) | 108.6 ± 37.8 | 111.6 ± 28.5 |
tmax (min) | 35.0 ± 12.2 | 50.8 ± 39.8 |
Cmax (ng/mL) | 332.7 ± 63.6 | 176.9 ± 55.1 ** |
CL (L·kg/min) | 2.3 ± 0.4 | 3.05 ± 0.54 |
Parameters (Unit) | AF under Normoxia | AF under Hypoxia |
---|---|---|
AUC(0→24 h) (ng/mL·min) | 8527.2 ± 2194 | 8299.0 ± 2202 |
MRT(0→24 h) (min) | 135.0 ± 29.3 | 129.5 ± 24.9 |
t1/2 (min) | 119.6 ± 29.7 | 131.5 ± 57.5 |
tmax (min) | 26.7 ± 8.2 | 35.0 ± 12.3 |
Cmax (ng/mL) | 70.3 ± 19.1 | 49.1 ± 16.2 |
CL (L·kg/min) | 1.7 ± 0.5 | 1.6 ± 0.7 |
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Xu, W.; Zhao, Y.; Qin, Y.; Ge, B.; Gong, W.; Wu, Y.; Li, X.; Zhao, Y.; Xu, P.; Xue, M. Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison. Molecules 2016, 21, 874. https://doi.org/10.3390/molecules21070874
Xu W, Zhao Y, Qin Y, Ge B, Gong W, Wu Y, Li X, Zhao Y, Xu P, Xue M. Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison. Molecules. 2016; 21(7):874. https://doi.org/10.3390/molecules21070874
Chicago/Turabian StyleXu, Weizhe, Yan Zhao, Yi Qin, Beikang Ge, Wenwen Gong, Yingting Wu, Xiaorong Li, Yuming Zhao, Pingxiang Xu, and Ming Xue. 2016. "Enhancement of Exposure and Reduction of Elimination for Paeoniflorin or Albiflorin via Co-Administration with Total Peony Glucosides and Hypoxic Pharmacokinetics Comparison" Molecules 21, no. 7: 874. https://doi.org/10.3390/molecules21070874