Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of Carthamus tinctorius Extract and Notoginseng Total Saponins
Abstract
1. Introduction
2. Materials and Methods
2.1. Plant Materials
2.2. Animals and Rat Liver Microsomes
2.3. Plasma Pharmacokinetic Studies
2.4. Incubation Procedure and CYP450 Activity Assay
2.5. LVDI-UHPLC-MS/MS Analysis
2.6. Method Validations
2.7. Data Processing
3. Results
3.1. Injection Solvent Optimization
3.2. Optimization of the Loading Phase for the LVDI-UHPLC-MS/MS-Based Method
3.3. Comparative Multiple-Component PK Studies
3.4. CYP450-Mediated Herb–Herb Interactions
3.5. Discussion
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Analyte | Group | t1/2 (h) | Tmax (h) | Cmax (ng·mL−1) | AUC0–t (ng·h·mL−1) | AUC0–∞ (ng·h·mL−1) |
---|---|---|---|---|---|---|
HSYA | CTE | 2.01 ± 0.34 | 0.88 ± 0.54 | 12.16 ± 3.09 | 33.05 ± 10.70 | 33.85 ± 10.78 |
CNP | 1.68 ± 0.79 | 1.17 ± 0.41 | 15.17 ± 4.39 | 38.33 ± 8.42 | 38.94 ± 8.60 | |
NGR1 | NGTS | 10.53 ± 3.06 | 1.15 ± 1.06 | 0.64 ± 0.18 | 6.30 ± 2.41 | 8.14 ± 3.60 |
CNP | 12.36 ± 4.48 | 1.04 ± 0.97 | 0.79 ± 0.18 | 8.12 ± 1.53 | 11.49 ±3.54 | |
GRb1 | NGTS | 36.89 ± 9.65 | 5.50 ± 1.80 | 113.08 ± 41.78 | 2317.66 ± 682.70 | 2808.87 ± 617.99 |
CNP | 34.47 ± 8.45 | 6.33 ± 3.45 | 129.00 ± 65.97 | 2472.33 ± 394.72 | 2816.01 ± 563.44 | |
GRd | NGTS | 42.75 ± 8.84 * | 4.50 ± 1.76 | 29.43 ± 10.69 | 460.90 ± 117.22 | 618.90 ± 157.23 |
CNP | 27.79 ± 6.94 | 6.33 ± 3.44 | 31.07 ± 16.78 | 459.04 ± 51.04 | 549.18 ± 58.09 | |
GRg1 | NGTS | 11.68 ± 2.09 * | 4.71 ± 3.71 | 0.78 ± 0.13 | 13.99 ± 5.03 | 16.72 ± 3.93 |
CNP | 15.11 ± 8.89 | 5.38 ± 4.66 | 1.04 ± 0.34 | 16.69 ± 3.42 | 20.23 ± 3.35 | |
GRe | NGTS | 5.25 ± 2.27 | 2.60 ± 0.89* | 0.29 ± 0.04* | 1.82 ± 0.19 | 2.90 ± 0.60 |
CNP | 5.99 ± 3.86 | 0.80 ± 0.41 | 0.39 ± 0.08 | 1.93 ± 0.19 | 3.33 ± 1.13 |
No. | IC50 (µg·mL−1/μM) # | ||||||
---|---|---|---|---|---|---|---|
CYP2C9 | CYP2E1 | CYP2C19 | CYP2D6 | CYP2B6 | CYP1A2 | CYP3A4 | |
CNP | 21.66 ± 1.15 | 31.85 ± 4.15 | 62.95 ± 1.17 | 25.27 ± 0.25 | 52.19 ± 2.24 | 26.36 ± 6.98 | 91.77 ± 5.16 |
CTE | 183.30 ± 17.98 | 35.47 ± 2.98 | >200 | 126.17 ± 17.63 | 58.09 ± 13.41 | 138.60 ± 14.36 | >200 |
NGTS | 9.32 ± 0.56 | 16.12 ± 2.59 | 40.85 ± 6.98 | 12.23 ± 4.25 | 43.90 ± 7.91 | 60.68 ± 2.26 | 106.27 ± 14.00 |
GRg1 (A1) | 36.49 ± 1.32 | 34.08 ± 4.76 | 78.12 ± 5.25 | 55.73 ± 6.08 | 11.02 ± 0.87 | 13.09 ± 8.24 | 39.25 ± 4.57 |
GRb1 (A2) | 17.57 ± 2.03 | 27.96 ± 2.39 | 16.80 ± 2.52 | 17.06 ± 1.29 | 120.83 ± 10.89 | 5.84 ± 0.14 | 30.04 ± 2.47 |
GRd (A3) | 73.01 ± 3.71 | 43.46 ± 0.06 | 71.36 ± 14.28 | 64.81 ± 11.68 | >200 | 4.36 ± 2.31 | 61.43 ± 14.32 |
GRe (A4) | >200 | 25.59 ± 9.03 | 50.53 ± 15.39 | >200 | 39.40 ± 4.81 | 94.41 ± 4.52 | 75.11 ± 7.24 |
NGR1 (A5) | 154.47 ± 16.65 | 121.70 ± 8.96 | 107.59 ± 29.58 | 20.42 ± 3.45 | >200 | 112.07 ± 7.72 | 84.59 ± 1.79 |
A6 | 55.84 ± 3.40 | 40.76 ± 1.65 | 53.67 ± 0.22 | 19.46 ± 2.83 | 114.70 ± 3.04 | 52.77 ± 1.93 | 26.45 ± 1.39 |
A7 | 80.47 ± 1.05 | 13.59 ± 0.60 | 18.50 ± 1.60 | 31.02 ± 4.17 | 177.17 ± 4.21 | 153.27 ± 8.73 | 126.70 ± 4.24 |
A8 | 1.21 ± 0.51 | 9.06 ± 1.85 | 111.26 ± 21.57 | 10.54 ± 1.11 | >200 | >200 | 34.38 ± 9.16 |
A9 (HSYA) | 0.17 ± 0.02 | 0.73 ± 0.15 | 49.33 ± 3.28 | 0.14 ± 0.06 | >200 | >200 | 9.42 ± 2.26 |
A10 | 39.06 ± 0.09 | >200 | >200 | >200 | >200 | >200 | >200 |
A11 | 24.92 ± 4.96 | 5.45 ± 1.37 | >200 | 64.55 ± 7.71 | 17.33 ± 0.96 | 53.17 ± 6.12 | 16.18 ± 4.30 |
A12 | >200 | >200 | >200 | 98.56 ± 12.30 | >200 | >200 | >200 |
A13 | 93.00 ± 2.56 | 10.22 ± 0.65 | 48.91 ± 4.36 | 37.12 ± 8.85 | 21.02 ± 2.31 | 13.35 ± 2.27 | 58.52 ± 0.66 |
A14 | >200 | >200 | >200 | >200 | >200 | >200 | >200 |
A15 | >200 | >200 | >200 | >200 | >200 | 127.47 ± 6.55 | >200 |
A16 | 13.48 ± 2.41 | 20.29 ± 4.13 | 46.35 ± 7.05 | 31.11 ± 3.91 | 68.48 ± 9.88 | 41.22 ± 3.18 | 73.74 ± 13.64 |
A17 | 14.92 ± 4.24 | 32.46 ± 5.79 | 70.38 ± 1.18 | 59.17 ± 1.01 | >200 | 21.46 ± 4.50 | 117.00 ± 6.77 |
A18 | 2.13 ± 0.64 | 4.27 ± 1.30 | 1.79 ± 0.52 | 0.98 ± 0.38 | 4.42 ± 1.31 | 0.12 ± 0.01 | 2.48 ± 0.48 |
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Chen, J.; Guo, X.; Lu, Y.; Shi, M.; Mu, H.; Qian, Y.; Wang, J.; Lu, M.; Zhao, M.; Tu, P.; et al. Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of Carthamus tinctorius Extract and Notoginseng Total Saponins. Pharmaceutics 2020, 12, 180. https://doi.org/10.3390/pharmaceutics12020180
Chen J, Guo X, Lu Y, Shi M, Mu H, Qian Y, Wang J, Lu M, Zhao M, Tu P, et al. Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of Carthamus tinctorius Extract and Notoginseng Total Saponins. Pharmaceutics. 2020; 12(2):180. https://doi.org/10.3390/pharmaceutics12020180
Chicago/Turabian StyleChen, Jinfeng, Xiaoyu Guo, Yingyuan Lu, Mengling Shi, Haidong Mu, Yi Qian, Jinlong Wang, Mengqiu Lu, Mingbo Zhao, Pengfei Tu, and et al. 2020. "Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of Carthamus tinctorius Extract and Notoginseng Total Saponins" Pharmaceutics 12, no. 2: 180. https://doi.org/10.3390/pharmaceutics12020180
APA StyleChen, J., Guo, X., Lu, Y., Shi, M., Mu, H., Qian, Y., Wang, J., Lu, M., Zhao, M., Tu, P., Song, Y., & Jiang, Y. (2020). Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of Carthamus tinctorius Extract and Notoginseng Total Saponins. Pharmaceutics, 12(2), 180. https://doi.org/10.3390/pharmaceutics12020180