Comparative Pharmacokinetic Study of Forchlorfenuron in Adult and Juvenile Rats
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimization of Sample Preparation
2.2. Optimization of LC and MS Conditions
2.3. Method Validation
2.4. Application in a Comparative PK Study of Rats
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Animals
3.3. Instrumentation and Chromatographic Conditions
3.4. Preparation of Standard and Quality Control Samples
3.5. Sample Preparation
3.6. Method Validation
3.7. PK Study
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Concentration of CPPU (ng/mL) | Intra-Assay | Inter-Assay | ||||
---|---|---|---|---|---|---|
Mean ± SD | Precision (%) | Accuracy (%) | Mean ± SD | Precision (%) | Accuracy (%) | |
20 | 20.6 ± 1.3 | 6.5 | 102.9 | 20.2 ± 1.1 | 5.4 | 101.2 |
60 | 61.4 ± 1.5 | 2.5 | 102.3 | 60.9 ± 0.5 | 0.9 | 101.5 |
1000 | 933.3 ± 18 | 1.9 | 93.3 | 952.8 ± 17.4 | 1.8 | 95.3 |
1600 | 1478.9± 12.2 | 0.8 | 92.5 | 1475.5 ± 6.4 | 0.4 | 92.2 |
Substance | Concentration of CPPU (ng/mL) | RE (%) | ME (%) |
---|---|---|---|
CPPU | 60 | 85.7 ± 0.4 | 90.5 ± 1.2 |
1000 | 82.5 ± 4.9 | 98.1 ± 3.2 | |
1600 | 93.1 ± 1.3 | 96.4 ± 1.1 | |
IS | 200 | 106.5 ± 5.3 | 108.3 ± 5.2 |
Spiked Samples (ng/mL) | 12 h (Benchtop) | 24 h (Autosampler) | 14 Days (at −20 °C) | Three Freeze-Thaw Cycles | ||||
---|---|---|---|---|---|---|---|---|
Mean ± SD | Accuracy (%) | Mean ± SD | Accuracy (%) | Mean ± SD | Accuracy (%) | Mean ± SD | Accuracy (%) | |
60 | 57.5 ± 1.7 | 95.9 | 58.5 ± 1.3 | 97.5 | 61.6 ± 0.9 | 102.7 | 61.4 ± 1.6 | 101.7 |
1000 | 974.6 ± 16.7 | 97.5 | 970.6 ± 8.4 | 97.1 | 1042.7 ± 23.1 | 104.3 | 1030.7 ± 12.1 | 103.1 |
1600 | 1564.9 ± 23.7 | 97.8 | 1546.3 ± 27.3 | 96.6 | 1664.4 ± 17.5 | 104.0 | 1632.9 ± 8.9 | 102.1 |
Animals | Dose (mg/kg) | Cmax (ng/mL) | T1/2 (h) | CLz (L/h/kg) | MRT0–t (h) | AUC0–t (ng /mL·h) | AUC0–∞ (ng /mL·h) | F (%) |
---|---|---|---|---|---|---|---|---|
Adult rats | 10 (p.o.) | 711.1 ± 70.4 | 2.6 ± 1.1 | 5.0 ± 1.3 | 3.0 ± 0.6 | 1935.7 ± 361.5 | 2108.3 ± 553.3 | 6.1 |
30 (p.o.) | 3266.3 ± 50.2 | 2.4 ± 1.1 | 3.4 ± 0.7 | 3.1 ± 0.6 | 9294.4 ± 862.0 | 9310.6 ± 867.7 | 9.8 | |
90 (p.o.) | 6273.3 ± 133.1 | 2.5 ± 0.8 | 4.6 ± 0.2 | 2.9 ± 0.1 | 18,915.9 ± 622.7 | 18,967.7 ± 643.2 | 6.6 | |
5 (i.v.) | 7977.4 ± 143.7 | 1.8 ± 0.1 | 0.3 ± 0.01 | 3.0 ± 0.1 | 15,851.6 ± 351.9 | 15,852.4 ± 352.8 | - | |
Juvenile rats | 10 (p.o.) | 1148.9 ± 145.1 ** | 2.6 ± 1.1 | 3.8 ± 0.9 | 2.6 ± 0.3 | 2745.5 ± 632.7 | 2753.6 ± 608.1 | 10.2 |
30 (p.o.) | 3386.1 ± 195.5 | 2.3 ± 0.2 | 2.8 ± 0.2 | 4.9 ± 0.1 *** | 10,713.5 ± 559.5 *** | 10,720.4 ± 563.4 *** | 13.3 | |
90 (p.o.) | 9805.7 ± 77.5 *** | 2.5 ± 0.1 | 2.5 ± 0.1 | 3.3 ± 0.1 *** | 36,442.7 ± 1086.1 *** | 36,513.9 ± 1085.8 *** | 15.1 | |
5 (i.v.) | 7571.2 ± 183.1 | 1.7 ± 0.4 | 0.3 ± 0.04 | 2.9 ± 0.3 | 13,470.0 ± 1281.6 | 13,471.3 ± 1280.4 | - |
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Ping, L.; Xu, B.; Zhou, Q.; Hong, Y.; Sun, Q.; Wang, J.; Zhu, D. Comparative Pharmacokinetic Study of Forchlorfenuron in Adult and Juvenile Rats. Molecules 2021, 26, 4276. https://doi.org/10.3390/molecules26144276
Ping L, Xu B, Zhou Q, Hong Y, Sun Q, Wang J, Zhu D. Comparative Pharmacokinetic Study of Forchlorfenuron in Adult and Juvenile Rats. Molecules. 2021; 26(14):4276. https://doi.org/10.3390/molecules26144276
Chicago/Turabian StylePing, Li, Bingyong Xu, Qian Zhou, Yawen Hong, Qingmei Sun, Jincheng Wang, and Difeng Zhu. 2021. "Comparative Pharmacokinetic Study of Forchlorfenuron in Adult and Juvenile Rats" Molecules 26, no. 14: 4276. https://doi.org/10.3390/molecules26144276