Determination of Bioactive Components in Chinese Herbal Formulae and Pharmacokinetics of Rhein in Rats by UPLC-MS/MS
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimization of LC-MS/MS Conditions
2.2. Determination of Bioactive Components in Commercial Pharmaceutical Herbal Products
Intra-day | Inter-day | |||||
---|---|---|---|---|---|---|
Nominal concentration (ng/mL) | Observed concentration (ng/mL) | Precision (% RSD) | Accuracy (% Bias) | Observed concentration (ng/mL) | Precision (% RSD) | Accuracy (% Bias) |
Emodin | ||||||
25 | 25.6 ± 3.84 | 2.53 | 14.9 | 25.7 ± 3.73 | 2.87 | 14.5 |
50 | 56.2 ± 4.87 | 12.4 | 8.67 | 55.4 ± 4.26 | 10.8 | 7.69 |
100 | 97.8 ± 2.01 | −2.21 | 2.06 | 98.4 ± 2.27 | −1.64 | 2.31 |
250 | 239 ± 5.31 | −4.10 | 2.22 | 241 ± 5.63 | −3.62 | 2.33 |
500 | 503 ± 3.09 | 0.65 | 0.61 | 504 ± 2.97 | 0.71 | 0.59 |
Rhein | ||||||
100 | 94.1 ± 10.7 | −5.86 | 11.3 | 103 ± 10.2 | 3.11 | 9.11 |
250 | 229 ± 24.9 | −8.37 | 10.9 | 226 ± 25.7 | −9.74 | 11.4 |
500 | 492 ± 64.8 | −1.56 | 13.2 | 506 ± 70.4 | 1.23 | 13.9 |
1000 | 1017 ± 99.6 | 1.72 | 9.79 | 992 ± 76.3 | −0.70 | 7.68 |
2500 | 2480 ± 144 | −0.77 | 5.82 | 2504 ± 138 | 0.19 | 5.51 |
Berberine | ||||||
100 | 94.3 ± 1.59 | 1.69 | −5.70 | 97.4 ± 7.26 | 7.46 | −2.60 |
250 | 259 ± 2.75 | 1.06 | 3.65 | 252 ± 17.5 | 6.96 | 0.67 |
500 | 497 ± 0.92 | 0.19 | −0.68 | 502 ± 13.2 | 0.62 | 0.40 |
Palmatine | ||||||
25 | 28.4 ± 3.48 | 12.3 | 13.5 | 26.2 ± 1.94 | 7.41 | 4.88 |
50 | 48.5 ± 2.36 | 4.86 | −3.01 | 48.5 ± 3.06 | 6.30 | −3.07 |
100 | 88.1 ± 1.52 | 1.73 | −11.9 | 92.3 ± 5.69 | 6.17 | −7.74 |
250 | 265 ± 8.49 | 3.20 | 6.16 | 265 ± 9.21 | 3.47 | 6.00 |
500 | 495 ± 3.80 | 0.77 | −1.06 | 495 ± 3.80 | 0.77 | −1.06 |
Baicalin | ||||||
50 | 56.3 ± 4.94 | 8.79 | 12.6 | 55.4 ± 4.20 | 7.59 | 10.8 |
100 | 95.4 ± 4.61 | 4.83 | −4.61 | 94.3 ± 5.27 | 5.59 | −5.69 |
250 | 247 ± 10.6 | 4.30 | −1.40 | 252 ± 5.05 | 2.01 | 0.75 |
500 | 503 ± 10.5 | 2.09 | 0.51 | 503 ± 10.4 | 2.07 | 0.58 |
Baicalein | ||||||
25 | 25.0 ± 1.40 | 5.61 | −0.17 | 25.9 ± 0.99 | 3.83 | 3.85 |
50 | 53.7 ± 4.62 | 8.61 | 7.43 | 54.8 ± 2.92 | 5.33 | 9.61 |
100 | 91.3 ± 6.68 | 7.32 | −8.70 | 92.8 ± 8.48 | 9.14 | −7.17 |
250 | 257 ± 18.9 | 7.40 | 2.69 | 249 ± 6.66 | 2.68 | −0.55 |
500 | 497 ± 19.9 | 4.01 | −0.52 | 506 ± 20.9 | 4.15 | 1.11 |
1000 | 1004 ± 13.7 | 1.36 | 0.41 | 1000 ± 16.6 | 1.66 | −0.01 |
Brand | Emodin(mg/g) | Rhein(mg/g) | Berberine(mg/g) | Palmatine(mg/g) | Baicalin(mg/g) | Baicalein(mg/g) |
---|---|---|---|---|---|---|
A | 0.23 ± 0.01 | 1.04 ± 0.04 | 29.2 ± 1.53 | 2.48 ± 0.08 | 56.0 ± 6.36 | 5.26 ± 0.32 |
B | 0.71 ± 0.02 | 2.38 ± 0.10 | 26.2 ± 1.60 | 2.13 ± 0.04 | 84.1 ± 3.48 | 16.6 ± 1.00 |
C | 0.39 ± 0.03 | 0.64 ± 0.06 | 35.8 ± 2.98 | 2.72 ± 0.16 | 36.9 ± 3.48 | 30.5 ± 1.63 |
D | 0.26 ± 0.01 | 0.49 ± 0.01 | 24.1 ± 1.06 | 2.29 ± 0.08 | 69.8 ± 4.04 | 3.69 ± 0.29 |
E | 0.55 ± 0.04 | 1.07 ± 0.11 | 28.5 ± 2.20 | 2.32 ± 0.09 | 66.4 ± 2.26 | 5.70 ± 0.46 |
F | 0.07 ± 0.00 | 0.06 ± 0.02 | 14.5 ± 0.65 | 1.11 ± 0.10 | 32.4 ± 0.81 | 6.53 ± 0.34 |
G | 0.17 ± 0.01 | ND | 21.0 ± 2.41 | 2.05 ± 0.08 | 18.7 ± 2.25 | 9.76 ± 2.65 |
H | 1.04 ± 0.04 | 2.29 ± 0.13 | 0.01 ± 0.02 | ND | 0.10 ± 0.00 | ND |
2.3. Method Validation of Rhein in Rat Plasma
Nominal concentration (ng/mL) | Set 1 | Set 2 | Set 3 | Matrix effect (%) | Recovery (%) |
---|---|---|---|---|---|
Rhein | |||||
100 | 201 ± 25 | 222 ± 34 | 211 ± 26 | 111 ± 17 | 95 ± 12 |
500 | 1464 ± 76 | 1497 ± 81 | 1322 ± 105 | 102 ± 6 | 88 ± 7 |
1000 | 2390 ± 158 | 2286 ± 157 | 2085 ± 98 | 96 ± 7 | 91 ± 4 |
Mean ± SD | 102.9 ± 7.6 | 91.6 ± 3.4 | |||
Ibuprofen (IS) | |||||
2500 | 3380 ± 143 | 2626 ± 147 | 2646 ± 184 | 77.7 ± 4.4 | 100.7 ± 7.0 |
Intra-day | Inter-day | |||||
---|---|---|---|---|---|---|
Nominal concentration (ng/mL) | Observed concentration (ng/mL) | Precision (% RSD) | Accuracy (% Bias) | Observed concentration (ng/mL) | Precision (% RSD) | Accuracy (% Bias) |
Rhein | ||||||
100 | 96.2 ± 9.48 | 9.86 | −3.83 | 104.4 ± 8.46 | 8.10 | 4.39 |
250 | 241 ± 20.5 | 8.51 | −3.70 | 229 ± 20.4 | 8.93 | −8.49 |
500 | 567 ± 81.4 | 14.34 | 13.43 | 499 ± 24.1 | 4.83 | −0.20 |
1000 | 1057 ± 143 | 13.50 | 5.67 | 1035 ± 129 | 12.5 | 3.47 |
2500 | 2491 ± 49.7 | 2.00 | −0.36 | 2505 ± 63.4 | 2.53 | 0.20 |
2.4. Comparative Pharmacokinetics of Rhein in Rats
PK parameters | Rhein | Rhubarb | SHXXT |
---|---|---|---|
11.9 mg/kg | 5.2 g/kg | 5 g/kg | |
Cmax (µg/mL) | 2.45 ± 0.55 | 4.34 ± 0.65 | 41.8 ± 10.7 * |
Tmax (min) | 25 ± 7.42 | 47.5 ± 7.2 * | 15 ± 0 |
T1/2 (min) | 144 ± 17.2 | 179 ± 25.9 | 50.2 ± 2.73 * |
AUC (min µg/mL) | 188 ± 36.4 | 419 ± 80.5 | 1712 ± 575 * |
CL (mL/min/kg) | 58 ± 7.89 | 25.7 ± 4.85 * | 9.22 ± 1.44 * |
MRT (min) | 112 ± 4.29 | 120 ± 9.12 | 50.2 ± 4.14 * |
Vss (L/kg) | 12.2 ± 2.10 | 6.03 ± 0.97 * | 0.69 ± 0.12 * |
3. Experimental
3.1. Chemicals and Reagents
3.2. LC-MS/MS
3.3. Quantitative Determination of Bioactive Components in Commercial Pharmaceutical Chinese Herbal Formulae, Sample Preparation, Method Validation and Sample Analysis
3.4. Method Validation of Rhein in Rat Plasma
RE (%) = C/B × 100
3.5. Pharmacokinetic Study of Rhein in Rats
3.6. Statistical Analysis
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Hou, M.-L.; Chang, L.-W.; Lin, C.-H.; Lin, L.-C.; Tsai, T.-H. Determination of Bioactive Components in Chinese Herbal Formulae and Pharmacokinetics of Rhein in Rats by UPLC-MS/MS. Molecules 2014, 19, 4058-4075. https://doi.org/10.3390/molecules19044058
Hou M-L, Chang L-W, Lin C-H, Lin L-C, Tsai T-H. Determination of Bioactive Components in Chinese Herbal Formulae and Pharmacokinetics of Rhein in Rats by UPLC-MS/MS. Molecules. 2014; 19(4):4058-4075. https://doi.org/10.3390/molecules19044058
Chicago/Turabian StyleHou, Mei-Ling, Li-Wen Chang, Chi-Hung Lin, Lie-Chwen Lin, and Tung-Hu Tsai. 2014. "Determination of Bioactive Components in Chinese Herbal Formulae and Pharmacokinetics of Rhein in Rats by UPLC-MS/MS" Molecules 19, no. 4: 4058-4075. https://doi.org/10.3390/molecules19044058