Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications
Abstract
:1. Introduction
2. Results and Discussion
2.1. LC-MS/MS Analysis
2.2. Preparation of Plasma Samples
2.3. Method Validation
2.3.1. Selectivity
2.3.2. Linearity and Lower Limit of Quantification
2.3.3. Precision and Accuracy
Concentration Added (ng/mL) | Concentration Observed (ng/mL) | Intra-day RSD (%) | Inter-Day RSD (%) | Accuracy (%) | ||
---|---|---|---|---|---|---|
First Day | Second Day | Third Day | ||||
3.03 | 3.03 ± 0.26 | 8.72 | - | - | - | 99.96 ± 8.71 |
6.06 | 5.84 ± 0.29 | 2.59 | 5.57 | 5.15 | 5.01 | 96.40 ± 4.82 |
181.68 | 172.96 ± 10.20 | 3.01 | 4.50 | 2.54 | 5.89 | 95.20 ± 5.61 |
363.36 | 347.91 ± 29.62 | 10.65 | 10.44 | 2.78 | 8.51 | 95.75 ± 8.15 |
2.3.4. Recovery and Matrix Effect
Drug | Concentration Added (ng/mL) | Recovery (R) | Matrix Effect (ME) | ||
---|---|---|---|---|---|
R (%) | RSD (%) | ME (%) | RSD (%) | ||
MP | 6.06 | 76.06 ± 3.38 | 4.45 | 93.67 ± 8.88 | 9.48 |
181.68 | 93.41 ± 2.47 | 2.64 | 100.85 ± 6.27 | 6.22 | |
363.36 | 95.25 ± 2.93 | 3.07 | 104.19 ± 5.71 | 5.48 | |
IS | 86.40 | 93.71 ± 2.29 | 2.44 | 97.54 ± 2.15 | 2.20 |
2.3.5. Stability
Conditions | Concentration Added (ng/mL) | Concentration Observed (ng/mL) | Accuracy (%) | RSD (%) |
---|---|---|---|---|
Long-term ( two months) | 6.06 | 5.97 ± 0.48 | 98.49 ± 7.91 | 8.03 |
181.68 | 177.06 ± 4.73 | 97.46 ± 2.60 | 2.67 | |
363.36 | 354.33 ± 6.27 | 97.52 ± 1.72 | 1.77 | |
Short-term (24 h) | 6.06 | 6.18 ± 0.23 | 102.13 ± 3.80 | 3.69 |
181.68 | 177.24 ± 1.60 | 97.56 ± 0.89 | 0.91 | |
363.36 | 360.98 ± 26.25 | 99.30 ± 7.25 | 7.27 | |
Frozen-thaw | 6.06 | 5.75 ± 0.36 | 95.01 ± 5.94 | 6.19 |
181.68 | 171.11 ± 8.31 | 94.18 ± 4.57 | 4.86 | |
363.36 | 342.22 ± 9.13 | 94.18 ± 2.51 | 2.66 | |
Post-preparative (24 h) | 6.06 | 5.74 ± 0.35 | 94.77 ± 5.87 | 6.16 |
181.68 | 176.92 ± 1.80 | 97.51 ± 1.22 | 1.02 | |
363.36 | 354.17 ± 7.67 | 97.47 ± 2.11 | 2.17 |
2.4. Pharmacokinetics Study of MP Tartrate Tablets in Beagle Dogs
Pharmacokinetic Parameters | Mean ± SD |
---|---|
AUC0-t (µg/L·h) | 919.88 ± 195.67 |
AUC0-∞ (µg/L·h) | 934.42 ± 200.92 |
MRT0-t (h) | 2.40 ± 0.19 |
MRT0-∞ (h) | 2.56 ± 0.17 |
t1/2 (h) | 1.73 ± 0.49 |
Tmax (h) | 0.96 ± 0.33 |
Cmax (ng/mL) | 349.12 ± 78.04 |
3. Experimental
3.1. Drugs and Reagents
3.2. Animals
3.3. LC-MS/MS Conditions and Instrumentation
3.4. Preparation of Standard and Quality Control Working Solutions
3.5. Preparation of Plasma Samples
3.6. Method Validation
3.6.1. Selectivity
3.6.2. Linearity and Lower Limit of Quantification
3.6.3. Precision and Accuracy
3.6.4. Recovery and Matrix Effect
3.6.5. Stability
3.7. Pharmacokinetics Study of MP Tartrate Tablets in Beagle Dogs
4. Conclusions
Acknowledgments
- Samples Availability: Please contact the authors.
References and Notes
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Li, S.; Wang, X.; Peng, K.; Ma, Z.; Zhang, X.; Fu, S.; Li, X.; Li, L.; Hong, A.; Jiang, J. Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications. Molecules 2012, 17, 2663-2674. https://doi.org/10.3390/molecules17032663
Li S, Wang X, Peng K, Ma Z, Zhang X, Fu S, Li X, Li L, Hong A, Jiang J. Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications. Molecules. 2012; 17(3):2663-2674. https://doi.org/10.3390/molecules17032663
Chicago/Turabian StyleLi, Sha, Xingli Wang, Kelong Peng, Zhiguo Ma, Xiaoqi Zhang, Shaolian Fu, Xiaofei Li, Linlin Li, Aihua Hong, and Jie Jiang. 2012. "Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications" Molecules 17, no. 3: 2663-2674. https://doi.org/10.3390/molecules17032663