LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin
Abstract
:1. Introduction
2. Results and Discussion
2.1. Method Development
2.2. Method Validation
2.2.1. Selectivity
2.2.2. Analytical Curve and Lower Limit of Quantification
2.2.3. Accuracy and Precision
2.2.4. Extraction Recovery and Matrix Effects
2.2.5. Stability
2.3. Application
2.3.1. Pharmacokinetic Study
2.3.2. Liver Tissue Distribution
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Animals
3.3. Chromatographic and Mass Spectrometry Conditions
3.4. Preparation of Calibration Standard and Quality Control Samples
3.5. Sample Preparation
3.6. Method Validation
3.7. Pharmacokinetic and Tissue Distribution
3.7.1. Pharmacokinetic Study
3.7.2. Liver Tissue Distribution Study
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Not available. |
Compounds | Q1 | Q3 | DP (V) | EP (V) | CE (V) | CXP (V) |
---|---|---|---|---|---|---|
Linarin | 591.3 | 283.3 | −120 | −10 | −22 | −17 |
Acacetin | 283.2 | 267.9 | −100 | −10 | −30 | −17 |
Apigenin | 269 | 117 | −45 | −10 | −45 | −17 |
p-Hydroxy benzaldehyde | 121 | 92.1 | −108 | −10 | −35 | −17 |
Luteolin-7-O-glucopyranoside (IS) | 447 | 285 | −40 | −10 | −37 | −17 |
Compounds | Analytical Curves | r | Linear Range (ng/mL) | LLOQ (ng/mL) | RSD (%) | RE (%) |
---|---|---|---|---|---|---|
Linarin | y = 0.00116x + 0.0011 | 0.9966 | 1.00–200 | 1.00 | 9.1 | −4.1 |
Acacetin | y = 0.171x + 0.0921 | 0.9951 | 1.00–200 | 1.00 | 3.6 | 5.2 |
Apigenin | y = 0.0875x + 0.0366 | 0.9974 | 1.00–200 | 1.00 | 6.4 | −0.6 |
p-Hydroxy benzaldehyde | y = 0.0767x + 0.1950 | 0.9955 | 1.00–200 | 1.00 | 7.2 | 3.1 |
Compounds | Added Concentration | Found Concentration | Intra-Day | Inter-Day | Accuracy | Recovery | Matrix Effect |
---|---|---|---|---|---|---|---|
(ng/mL) | (ng/mL) | RSD (%) | RSD (%) | RE (%) | (%) | (%) | |
Linarin | 3.00 | 2.97 ± 0.29 | 9.3 | 13.3 | −0.9 | 60.9 ± 8.3 | 88.1 ± 7.8 |
25.0 | 24.3 ± 2.35 | 8.0 | 14.6 | −2.9 | 62.0 ± 6.8 | 102.8 ± 3.3 | |
160 | 155 ± 12.1 | 7.9 | 7.3 | −3.2 | 60.5 ± 4.7 | 94.1 ± 2.0 | |
Acacetin | 3.00 | 2.87 ± 0.18 | 6.6 | 4.2 | −4.5 | 76.1 ± 3.6 | 106.8 ± 5.5 |
25.0 | 24.8 ± 0.94 | 3.3 | 6.4 | −0.8 | 72.7 ± 1.3 | 104.1 ± 3.1 | |
160 | 163 ± 5.30 | 3.3 | 2.9 | 2.0 | 73.9 ± 1.6 | 104.1 ± 1.0 | |
Apigenin | 3.00 | 2.89 ± 0.22 | 8.0 | 4.3 | −3.8 | 71.3 ± 3.8 | 105.4 ± 6.5 |
25.0 | 24.4 ± 1.06 | 2.6 | 10.6 | −2.5 | 72.4 ± 1.3 | 104.1 ± 1.9 | |
160 | 161 ± 7.86 | 3.1 | 11.4 | 0.4 | 74.0 ± 1.8 | 102.6 ± 1.7 | |
p-Hydroxy benzaldehyde | 3.00 | 2.97 ± 0.23 | 7.2 | 6.8 | −0.9 | 61.0 ± 2.4 | 107.9 ± 7.8 |
25.0 | 24.9 ± 1.39 | 4.8 | 9.8 | −0.4 | 68.3 ± 2.7 | 101.9 ± 3.0 | |
160 | 166 ± 10.9 | 4.0 | 14.5 | 3.7 | 63.6 ± 1.0 | 104.3 ± 7.2 | |
Luteolin-7-O-glucopyranoside (IS) | 50.0 | - | - | - | - | 48.9 ± 1.4 | 108.4 ± 3.1 |
Compounds | Added Concentration | Post-Preparative Stability | Short-Term Stability | Freeze-Thaw Stability | Long-Term Stability | ||||
---|---|---|---|---|---|---|---|---|---|
(ng/mL) | RE (%) | RSD (%) | RE (%) | RSD (%) | RE (%) | RSD (%) | RE (%) | RSD (%) | |
Linarin | 3.00 | 7.0 | 3.7 | 5.3 | 8.9 | −7.3 | 7.9 | 9.7 | 4.6 |
160 | −8.5 | 5.8 | −8.5 | 1.5 | −3.5 | 9.1 | 2.3 | 4.8 | |
Acacetin | 3.00 | −7.0 | 3.9 | −8.0 | 7.6 | −1.3 | 5.7 | −5.0 | 2.5 |
160 | 3.3 | 5.0 | 7.9 | 6.4 | 4.4 | 2.4 | 2.9 | 2.3 | |
Apigenin | 3.00 | 6.0 | 11.0 | −10.0 | 0.7 | −7.0 | 3.9 | −3.3 | 4.8 |
160 | −4.8 | 3.5 | 10.6 | 6.7 | 6.0 | 1.4 | 4.2 | 0.7 | |
p-Hydroxy | 3.00 | 7.7 | 4.0 | 11.3 | 3.3 | −4.3 | 9.1 | −7.0 | 3.2 |
benzaldehyde | 160 | 0.4 | 6.1 | 7.3 | 4.2 | 11.5 | 3.7 | 9.4 | 3.0 |
Parameters | Linarin | Acacetin | ||
---|---|---|---|---|
Normal Rats | Model Rats | Normal Rats | Model Rats | |
t1/2z (h) | 36.9 ± 21.8 | 37.4 ± 27.9 | 16.5 ± 3.7 | 11.0 ± 6.1 |
Tmax (h) | 0.12 ± 0.10 | 8.65 ± 5.17 | 15.13 ± 13.83 | 12.25 ± 5.28 |
Cmax (μg/L) | 14.40 ± 4.37 | 13.85 ± 4.47 | 16.78 ± 14.30 | 41.65 ± 30.77 |
AUC0–t (μg/L·h) | 174 ± 54 | 352 ± 99 | 282 ± 116 | 839 ± 682 |
AUC0–∞ (μg/L·h) | 250 ± 52 | 367 ± 51 | 340 ± 128 | 919 ± 658 |
Vz/F (L/kg) | 22517 ± 14103 | 9077 ± 4335 | 11233 ± 7029 | 2595 ± 2117 |
CLz/F (L/h/kg) | 335 ± 145 | 225 ± 77 | 322 ± 187 | 149 ± 91 |
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Li, Y.; Guang, C.; Zhao, N.; Feng, X.; Qiu, F. LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin. Molecules 2019, 24, 3342. https://doi.org/10.3390/molecules24183342
Li Y, Guang C, Zhao N, Feng X, Qiu F. LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin. Molecules. 2019; 24(18):3342. https://doi.org/10.3390/molecules24183342
Chicago/Turabian StyleLi, Yang, Chenxi Guang, Na Zhao, Xinchi Feng, and Feng Qiu. 2019. "LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin" Molecules 24, no. 18: 3342. https://doi.org/10.3390/molecules24183342
APA StyleLi, Y., Guang, C., Zhao, N., Feng, X., & Qiu, F. (2019). LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin. Molecules, 24(18), 3342. https://doi.org/10.3390/molecules24183342