A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study
Abstract
:1. Introduction
2. Results and Discussion
2.1. UPLC-MS/MS Method Development
2.2. UPLC-MS/MS Method Validation
2.2.1. Selectivity
2.2.2. Calibration Curve and LLOQ
2.2.3. Precision and Accuracy
2.2.4. Matrix Effect and Extraction Recovery
2.2.5. Stability
2.3. Pharmacokinetic Interaction of TEL with LEN
3. Materials and Methods
3.1. Drugs and Reagents
3.2. Chromatographic Equipment and Conditions
3.3. Mass Spectrometry Equipment and Conditions
3.4. Preparation of Stock Solution and Working Solution
3.5. Preparation of Calibration Standards and Quality Control (QC) Samples
3.6. Plasma Sample Preparation
3.7. Method Validation
3.7.1. Selectivity
3.7.2. Calibration Curve and LLOQ
3.7.3. Precision and Accuracy
3.7.4. Matrix Effect and Extraction Recovery
3.7.5. Stability
3.8. Application to Pharmacokinetic and Drug-Drug Interaction Study in Rats
3.9. Statistical Analysis
4. 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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Analytes | Concentration (ng/mL) | Intra-Batch (n = 6) | Inter-Batch (n = 18) | ||||
---|---|---|---|---|---|---|---|
Mean ± SD | RSD (%) | RE (%) | Mean ± SD | RSD (%) | RE (%) | ||
LEN | 0.2 | 0.20 ± 0.01 | 7.09 | 0.08 | 0.21 ± 0.02 | 9.58 | 5.06 |
0.5 | 0.51 ± 0.02 | 3.29 | 2.47 | 0.50 ± 0.03 | 5.28 | 0.22 | |
150 | 155.00 ± 8.15 | 5.26 | 3.33 | 151.11 ± 7.61 | 5.03 | 0.74 | |
800 | 810.33 ± 13.94 | 1.72 | 1.29 | 788.83 ± 28.50 | 3.61 | −1.40 | |
TEL | 0.1 | 0.11 ± 0.01 | 6.68 | 6.45 | 0.11 ± 0.01 | 5.88 | 5.94 |
0.25 | 0.25 ± 0.01 | 2.93 | 1.27 | 0.25 ± 0.01 | 3.86 | −0.31 | |
75 | 75.10 ± 2.77 | 3.69 | 0.13 | 76.27 ± 4.38 | 5.75 | 1.70 | |
400 | 393.50 ± 14.18 | 3.60 | −1.63 | 394.22 ± 18.98 | 4.81 | −1.44 |
Analytes | Concentration (ng/mL) | Matrix Effect | Extraction Recovery | ||
---|---|---|---|---|---|
Mean ± SD (%) | RSD (%) | Mean ± SD (%) | RSD (%) | ||
LEN | 0.5 | 106.79 ± 6.54 | 6.12 | 106.57 ± 5.99 | 5.62 |
150 | 100.30 ± 8.40 | 8.38 | 97.94 ± 2.80 | 2.86 | |
800 | 100.80 ± 8.03 | 7.97 | 99.43 ± 11.59 | 11.65 | |
TEL | 0.25 | 109.29 ± 5.09 | 4.66 | 104.05 ± 5.37 | 5.16 |
75 | 107.16 ± 6.48 | 6.05 | 96.04 ± 4.73 | 4.93 | |
400 | 105.77 ± 6.37 | 6.02 | 101.99 ± 10.61 | 10.40 |
Analytes | Conditions | Concentration (ng/mL) | Mean ± SD (ng/mL) | Precision (RSD%) | Accuracy (RE%) |
---|---|---|---|---|---|
LEN | Autosampler for 24 h | 0.5 | 0.48 ± 0.03 | 6.65 | −3.30 |
150 | 148.33 ± 6.06 | 4.08 | −1.11 | ||
800 | 835.67 ± 34.60 | 4.14 | 4.46 | ||
Room temperature for 8 h | 0.5 | 0.52 ± 0.03 | 5.82 | 4.57 | |
150 | 149.33 ± 11.15 | 7.46 | −0.44 | ||
800 | 751.50 ± 19.74 | 2.63 | −6.06 | ||
−80 °C for 30 days | 0.5 | 0.53 ± 0.05 | 8.81 | 5.67 | |
150 | 154.00 ± 4.77 | 3.10 | 2.67 | ||
800 | 808.00 ± 59.16 | 7.32 | 1.00 | ||
Freeze–thaw stability for three times | 0.5 | 0.48 ± 0.05 | 10.53 | −3.17 | |
150 | 150.17 ± 14.85 | 9.89 | 0.11 | ||
800 | 787.50 ± 40.13 | 5.10 | −1.56 | ||
TEL | Autosampler for 24 h | 0.25 | 0.24 ± 0.02 | 6.61 | −4.33 |
75 | 73.68 ± 1.59 | 2.16 | −1.76 | ||
400 | 398.50 ± 22.76 | 5.71 | −0.38 | ||
Room temperature for 8 h | 0.25 | 0.24 ± 0.01 | 5.18 | −3.53 | |
75 | 73.23 ± 5.40 | 7.37 | −2.36 | ||
400 | 369.67 ± 6.98 | 1.89 | −7.58 | ||
−80 °C for 30 days | 0.25 | 0.25 ± 0.01 | 5.05 | 1.80 | |
75 | 74.73 ± 1.64 | 2.20 | −0.36 | ||
400 | 401.50 ± 27.46 | 6.84 | 0.38 | ||
Freeze–thaw stability for three times | 0.25 | 0.25 ± 0.01 | 3.21 | −0.47 | |
75 | 72.35 ± 2.51 | 3.47 | −3.53 | ||
400 | 391.33 ± 25.73 | 6.57 | −2.17 |
Parameters (Unit) | LEN (1.2 mg/kg) | TEL (4 mg/kg) | ||
---|---|---|---|---|
Alone | with TEL (4 mg/kg) | Alone | with LEN (1.2 mg/kg) | |
AUC0–t (ug/L*h) | 5665.51 ± 602.61 | 5859.99 ± 1350.86 | 4146.02 ± 1035.68 | 2284.10 ± 322.18 ** |
AUC0–∞ (ug/L*h) | 5666.29 ± 602.95 | 5863.68 ± 1350.05 | 4180.86 ± 1035.24 | 2455.98 ± 544.34 ** |
Cmax (ug/L) | 497.83 ± 106.93 | 644.50 ± 210.71 | 171.33 ± 38.05 | 98.98 ± 19.30 ** |
Tmax (h) | 2.5 (0.85–8.5) | 1.5 (0.88–3.25) | 8 (7.5–12) | 11 (7.5–12) |
t1/2z (h) | 8.75 ± 2.55 | 9.32 ± 4.69 | 9.36 ± 2.09 | 12.43 ± 12.71 |
CLz (L/h/kg) | 0.21 ± 0.02 | 0.22 ± 0.05 | 1.00 ± 0.21 | 1.69 ± 0.35 ** |
Vz (L/kg) | 2.69 ± 0.79 | 2.92 ± 1.60 | 13.49 ± 3.97 | 26.59 ± 19.50 * |
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Cui, Y.; Li, Y.; Li, X.; Fan, L.; He, X.; Fu, Y.; Dong, Z. A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study. Molecules 2022, 27, 1291. https://doi.org/10.3390/molecules27041291
Cui Y, Li Y, Li X, Fan L, He X, Fu Y, Dong Z. A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study. Molecules. 2022; 27(4):1291. https://doi.org/10.3390/molecules27041291
Chicago/Turabian StyleCui, Yanjun, Ying Li, Xiao Li, Liju Fan, Xueru He, Yuhao Fu, and Zhanjun Dong. 2022. "A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study" Molecules 27, no. 4: 1291. https://doi.org/10.3390/molecules27041291