Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS
Abstract
:1. Introduction
2. Results
2.1. Method Validation
2.1.1. Selectivity
2.1.2. Linearity and Sensitivity
2.1.3. Precision and Accuracy
2.1.4. Extraction Recovery and Matrix Effect
2.1.5. Stability
2.2. Pharmacokinetic Analysis and Bioavailability
2.3. Tissue Distribution Study
2.4. Excretory Study
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Animals
4.3. Instrumentation and Analytical Conditions
4.4. Preparation of Calibration Standards and Quality Control Samples
4.4.1. Plasma Pharmacokinetic Study
4.4.2. Tissue Distribution Study
4.4.3. Excretion Study
4.5. Sample Preparation
4.5.1. Preparation of Plasma Samples
4.5.2. Preparation of Tissue Samples
4.5.3. Preparation of Fecal Samples
4.5.4. Preparation of Urine Samples
4.6. Method Validation
4.6.1. Specificity
4.6.2. Linearity
4.6.3. Accuracy and Precision
4.6.4. Extraction Recovery and Matrix Effect
4.6.5. Stability
4.7. Pharmacokinetic Study
4.7.1. Preparation of Drug Solution
4.7.2. Plasma Pharmacokinetic Study
4.7.3. Tissue Distribution Study
4.7.4. Excretory Study
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Matrix | Equation | Range (ng/mL) | LLOQ (ng/mL) |
---|---|---|---|
Plasma | y = 0.018x + 0.006 (r2 = 0.9991) | 5–200 | 5 |
Heart | y = 0.014x + 0.014 (r2 = 0.9986) | 5–1000 | 5 |
Liver | y = 0.017x + 0.012 (r2 = 0.9997) | 5–1000 | 5 |
Spleen | y = 0.016x + 0.003 (r2 = 0.9993) | 5–1000 | 5 |
Lung | y = 0.014x − 0.004 (r2 = 0.9997) | 5–1000 | 5 |
Kidney | y = 0.015x + 0.012 (r2 = 0.9997) | 5–1000 | 5 |
Brain | y = 0.014x + 0.010 (r2 = 0.9997) | 5–1000 | 5 |
Urine | y = 0.014x + 0.016 (r2 = 0.9910) | 5–1000 | 5 |
Feces | y = 0.010x + 0.017 (r2 = 0.9991) | 5–1000 | 5 |
Matrix | Spiked (ng/mL) | Precision (RSD, %) | Accuracy (%) (n = 6) | |
---|---|---|---|---|
Intra-Day (n = 6) | Inter-Day (n = 18) | |||
Plasma | 5 | 5.07 | 3.64 | 104.28 |
10 | 1.21 | 2.90 | 102.97 | |
50 | 0.49 | 1.22 | 101.02 | |
160 | 0.20 | 0.95 | 102.87 | |
Heart | 5 | 7.67 | 8.48 | 98.10 |
10 | 5.69 | 7.18 | 94.41 | |
100 | 8.15 | 7.73 | 97.21 | |
800 | 3.73 | 6.52 | 96.03 | |
Liver | 5 | 6.05 | 7.44 | 104.82 |
10 | 7.93 | 7.49 | 105.2 | |
100 | 2.11 | 5.39 | 102.62 | |
800 | 4.31 | 5.51 | 98.51 | |
Spleen | 5 | 7.40 | 9.68 | 105.13 |
10 | 7.56 | 7.22 | 105.20 | |
100 | 6.06 | 6.45 | 95.86 | |
800 | 5.76 | 5.32 | 92.84 | |
Lung | 5 | 8.91 | 7.34 | 101.26 |
10 | 10.48 | 9.35 | 102.64 | |
100 | 5.74 | 4.64 | 102.19 | |
800 | 3.36 | 4.17 | 96.94 | |
Kidney | 5 | 7.82 | 11.62 | 98.10 |
10 | 7.05 | 9.01 | 94.41 | |
100 | 7.56 | 6.12 | 97.21 | |
800 | 4.91 | 3.63 | 96.03 | |
Brain | 5 | 10.6 | 9.65 | 100.78 |
10 | 5.54 | 7.11 | 104.69 | |
100 | 5.95 | 4.47 | 97.21 | |
800 | 4.85 | 4.42 | 95.41 | |
Feces | 5 | 6.32 | 8.31 | 102.15 |
10 | 5.61 | 4.46 | 101.12 | |
100 | 4.77 | 4.12 | 99.88 | |
800 | 4.85 | 4.42 | 99.28 | |
Urine | 5 | 4.95 | 9.79 | 94.79 |
10 | 11.71 | 8.97 | 101.10 | |
100 | 6.33 | 5.51 | 102.59 | |
800 | 3.34 | 3.30 | 102.41 |
Matrix | Nominal Concentration (ng/mL) | Extraction Recovery (%, Mean ± SD) | Matrix Effect (%, Mean ± SD) |
---|---|---|---|
Plasma | 10 | 99.35 ± 3.96 | 100.86 ± 6.30 |
50 | 96.87 ± 3.54 | 97.54 ± 5.36 | |
160 | 100.46 ± 1.39 | 101.74 ± 2.51 | |
Heart | 10 | 109.91 ± 2.26 | 98.36 ± 7.52 |
100 | 101.73 ± 6.38 | 95.70 ± 5.72 | |
800 | 108.08 ± 5.24 | 102.58 ± 5.94 | |
Liver | 10 | 108.07 ± 3.93 | 104.24 ± 7.71 |
100 | 102.23 ± 5.91 | 98.77 ± 7.49 | |
800 | 100.78 ± 1.81 | 101.45 ± 6.33 | |
Spleen | 10 | 108.04 ± 3.71 | 104.32 ± 6.70 |
100 | 106.63 ± 3.29 | 99.73 ± 7.54 | |
800 | 99.06 ± 6.10 | 102.91 ± 7.31 | |
Lung | 10 | 103.24 ± 3.69 | 101.01 ± 7.01 |
100 | 98.48 ± 4.10 | 96.42 ± 6.99 | |
800 | 100.72 ± 3.93 | 100.70 ± 4.92 | |
Kidney | 10 | 104.75 ± 5.60 | 99.93 ± 6.65 |
100 | 94.34 ± 3.61 | 99.31 ± 5.95 | |
800 | 102.33 ± 5.30 | 102.62 ± 6.16 | |
Brain | 10 | 106.15 ± 8.78 | 102.61 ± 4.27 |
100 | 100.90 ± 5.46 | 99.36 ± 7.68 | |
800 | 98.91 ± 2.42 | 94.48 ± 4.40 | |
Feces | 10 | 97.99 ± 6.50 | 101.85 ± 6.02 |
100 | 103.99 ± 2.20 | 100.19 ± 3.87 | |
800 | 101.44 ± 0.94 | 102.58 ± 6.21 | |
Urine | 10 | 106.49 ± 3.78 | 99.57 ± 8.17 |
100 | 107.78 ± 5.96 | 98.84 ± 3.85 | |
800 | 105.40 ± 6.55 | 104.49 ± 6.57 |
Matrix | Spiked (ng/mL) | 24 h (Automatic Sampler) | Freeze–Thaw at −20 °C | Stored at −20 °C for 30 Days | |||
---|---|---|---|---|---|---|---|
Precision (%, RSD) | Accuracy (%) | Precision (%, RSD) | Accuracy (%) | Precision (%, RSD) | Accuracy (%) | ||
Plasma | 10 | 4.61 | 100.97 | 1.48 | 97.20 | 9.15 | 101.09 |
160 | 0.49 | 99.92 | 1.70 | 99.79 | 5.02 | 97.03 | |
Heart | 10 | 7.15 | 107.09 | 5.24 | 95.63 | 5.85 | 94.72 |
800 | 7.20 | 106.65 | 9.77 | 99.82 | 4.11 | 97.51 | |
Liver | 10 | 11.41 | 99.32 | 9.92 | 94.59 | 9.77 | 99.60 |
800 | 7.45 | 96.3 | 7.35 | 99.63 | 4.56 | 100.98 | |
Spleen | 10 | 8.62 | 101.97 | 15.39 | 103.61 | 6.45 | 99.67 |
800 | 8.55 | 92.34 | 7.14 | 97.54 | 2.51 | 98.02 | |
Lung | 10 | 15.86 | 98.59 | 9.88 | 97.42 | 6.06 | 98.89 |
800 | 5.92 | 102.03 | 4.64 | 101.74 | 2.78 | 103.02 | |
Kidney | 10 | 14.83 | 103.91 | 18.22 | 99.06 | 7.44 | 98.10 |
800 | 6.78 | 103.48 | 6.54 | 101.88 | 6.37 | 97.36 | |
Brain | 10 | 8.17 | 102.78 | 12.88 | 103.21 | 8.06 | 98.22 |
800 | 4.54 | 97.04 | 3.95 | 95.94 | 6.62 | 94.08 | |
Feces | 10 | 6.51 | 99.33 | 7.90 | 100.5 | 6.44 | 94.98 |
800 | 4.54 | 97.04 | 3.95 | 95.94 | 5.13 | 96.50 | |
Urine | 10 | 18.88 | 100.84 | 15.33 | 96.55 | 4.34 | 99.57 |
800 | 4.72 | 100.47 | 4.62 | 98.70 | 3.93 | 100.46 |
PK Parameters | I.V (1.92 mg/kg) | P.O (15 mg/kg) |
---|---|---|
AUC0–24 (ng/mL × h) | 540.14 ± 43.71 | 427.95 ± 66.09 |
AUC0–∞ (ng/mL × h) | 599.20 ± 31.78 | 502.93 ± 77.72 |
T1/2 (h) | 3.50 ± 2.24 | 9.16 ± 0.90 |
CL (mL/h × kg) | 1.61 ± 0.09 | 30.48 ± 5.28 |
V (mL/kg) | 4.03 ± 1.80 | 401.70 ± 69.59 |
Cmax (ng/mL) | 691.20 ± 119.86 | 153.48 ± 15.93 |
Tmax (h) | 0.083 ± 0.00 | 0.75 ± 0.18 |
F (%) | / | 10.70 ± 1.72 |
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Guo, Z.; Gao, B.; Fan, M.; Chen, L.; Zhang, C.; Liang, X.; Su, W.; Xie, Y. Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS. Molecules 2023, 28, 2377. https://doi.org/10.3390/molecules28052377
Guo Z, Gao B, Fan M, Chen L, Zhang C, Liang X, Su W, Xie Y. Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS. Molecules. 2023; 28(5):2377. https://doi.org/10.3390/molecules28052377
Chicago/Turabian StyleGuo, Zili, Bianbian Gao, Miaoliang Fan, Lisha Chen, Changjun Zhang, Xianrui Liang, Weike Su, and Yuanyuan Xie. 2023. "Study on Absorption, Distribution and Excretion of a New Candidate Compound XYY-CP1106 against Alzheimer’s Disease in Rats by LC-MS/MS" Molecules 28, no. 5: 2377. https://doi.org/10.3390/molecules28052377