Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS
Abstract
:1. Introduction
2. Experimental Results
2.1. Method Validation
2.1.1. Specificity Test
2.1.2. Calibration Curve and Linear Range
2.1.3. Precision and Accuracy
2.1.4. Substrate Effect and Extraction Recoveries
2.1.5. Stability Test
2.2. Pharmacokinetic Analysis of Control Group
2.3. Pharmacokinetic Study of JYPs in ADHD Model Group
2.4. Pharmacokinetic Comparison of JYPs in Control Rats and ADHD Model Rats
3. Materials and Methods
3.1. Chemical and Reagents
3.2. Instruments
3.3. Experimental Animals
3.4. Preparation of JYP Gavage Solution
3.5. Preparation of Control Solution
3.6. Drug Administration
3.7. Pretreatment of Biological Samples
3.8. Chromatography–Mass Spectrometry Detection Conditions
3.9. Method Validation
3.10. Statistical Analyses and Data Processing
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Compound | Calibration Curve | Linear Range (ng/mL) | r |
---|---|---|---|
Saikosaponin A | y = 0.0039x + 0.0527 | 0.53–334.12 | 0.9944 |
Saikosaponin D | y = 0.0039x + 0.0172 | 0.47–298.65 | 0.9979 |
Z-Ligustilide | y = 0.0164x + 0.3872 | 0.39–99.72 | 0.9977 |
Levistilide A | y = 0.0249x + 0.5986 | 0.26–133.65 | 0.9954 |
Ferulic acid | y = 0.0017x + 0.0083 | 0.44–275.83 | 0.9993 |
Liquiritigenin | y = 0.0265x + 0.1190 | 0.22–109.96 | 0.9992 |
Liquiritin | y = 0.018x + 0.0918 | 0.39–99.8 | 0.9993 |
Paeoniflorin | y = 0.0001x + 0.0038 | 0.37–231.77 | 0.9944 |
Albiflorin | y = 0.0003x − 0.0012 | 0.37–236.9 | 0.9980 |
Oxypaeoniflorin | y = 0.0012x + 0.0076 | 0.44–110.4 | 0.9986 |
Poricoic acid A | y = 0.0105x + 0.2400 | 0.42–107.04 | 0.9959 |
Poricoic acid B | y = 0.0045x + 0.0166 | 0.45–114.7 | 0.9986 |
Licochalcone A | y = 0.1271x + 0.2547 | 0.21–107.91 | 0.9987 |
Compound | Concentration | Intra-Day | Inter-Day | ||||
---|---|---|---|---|---|---|---|
Mean ± SD | Accuracy | Precision | Mean ± SD | Accuracy | Precision | ||
ng/mL | ng/mL | RE, % | RSD, % | ng/mL | RE, % | RSD, % | |
Saikosaponin A | 334.12 | 338.83 ± 10.69 | 1.41 | 3.16 | 336.59 ± 25.59 | 6.66 | 1.46 |
167.06 | 167.65 ± 5.61 | 0.35 | 3.35 | 163.66 ± 4.12 | 1.42 | 4.16 | |
0.53 | 0.50 ± 0.02 | −6.17 | 3.58 | 0.52 ± 0.03 | −2.64 | 6.19 | |
Saikosaponin D | 298.65 | 286.23 ± 7.83 | −4.16 | 2.74 | 283.88 ± 11.11 | −4.94 | 3.91 |
149.32 | 136.60 ± 6.17 | 0.32 | 4.52 | 143.01 ± 7.40 | 0.32 | 5.17 | |
0.48 | 0.42 ± 0.02 | 1.71 | 4.82 | 0.44 ± 0.03 | 1.71 | 6.68 | |
Z-Ligustilide | 99.72 | 103.01 ± 4.68 | 3.29 | 4.54 | 99.43 ± 4.54 | 3.30 | 2.46 |
49.86 | 50.42 ± 1.64 | 1.13 | 3.25 | 45.16 ± 3.20 | 0.83 | 2.58 | |
0.20 | 0.20 ± 0.01 | −2.22 | 5.45 | 0.19 ± 0.01 | −4.13 | 3.27 | |
Levistilide A | 133.65 | 137.57 ± 4.37 | 2.93 | 3.18 | 133.81 ± 5.30 | 0.12 | 3.96 |
66.82 | 64.34 ± 2.92 | −3.72 | 4.54 | 61.59 ± 3.90 | −7.82 | 6.32 | |
0.26 | 0.24 ± 0.01 | −7.88 | 3.87 | 0.24 ± 0.02 | −4.43 | 5.88 | |
Ferulic acid | 275.83 | 280.29 ± 5.39 | 1.62 | 1.92 | 270.57 ± 16.60 | −1.91 | 6.14 |
137.92 | 135.87 ± 7.97 | −1.49 | 5.86 | 135.87 ± 7.97 | −5.61 | 8.78 | |
0.44 | 0.43 ± 0.02 | −2.96 | 4.65 | 0.41 ± 0.06 | −3.93 | 5.65 | |
Liquiritigenin | 109.96 | 111.12 ± 2.31 | 1.05 | 2.08 | 106.17 ± 4.74 | −2.73 | 4.67 |
54.98 | 54.13 ± 2.46 | −1.54 | 4.54 | 52.07 ± 4.78 | −1.87 | 4.31 | |
0.22 | 0.21 ± 0.00 | −6.13 | 1.30 | 0.21 ± 0.02 | −4.39 | 5.98 | |
Liquiritin | 99.80 | 104.48 ± 1.90 | 4.69 | 1.82 | 99.16 ± 3.72 | −0.64 | 3.75 |
49.90 | 48.44 ± 3.11 | −2.92 | 6.42 | 46.29 ± 1.78 | −7.24 | 3.84 | |
0.39 | 0.36 ± 0.01 | −7.90 | 3.24 | 0.37 ± 0.02 | −4.45 | 5.63 | |
Paeoniflorin | 237.77 | 230.19 ± 13.02 | −3.19 | 5.66 | 236.63 ± 16.46 | −0.48 | 6.96 |
115.89 | 106.94 ± 4.70 | −7.72 | 4.39 | 102.51 ± 8.40 | 6.05 | 2.40 | |
0.37 | 0.40 ± 0.01 | 8.98 | 3.70 | 0.35 ± 0.02 | −0.68 | 4.73 | |
Albiflorin | 236.90 | 230.32 ± 8.11 | −2.78 | 3.52 | 236.71 ± 11.63 | −0.08 | 4.91 |
118.45 | 122.04 ± 2.41 | 3.03 | 1.98 | 105.95 ± 6.58 | 1.56 | 3.60 | |
0.37 | 0.36 ± 0.02 | −2.48 | 4.44 | 0.35 ± 0.02 | −4.98 | 4.65 | |
Oxypaeoniflorin | 110.40 | 109.05 ± 1.12 | −1.22 | 1.03 | 106.90 ± 5.92 | 2.95 | 2.42 |
55.20 | 53.77 ± 2.82 | −2.59 | 5.25 | 48.93 ± 2.48 | −0.71 | 3.55 | |
0.44 | 0.42 ± 0.01 | −4.23 | 2.52 | 0.44 ± 0.02 | −0.68 | 4.17 | |
Poricoic acid A | 107.04 | 104.64 ± 5.37 | −2.25 | 5.14 | 105.15 ± 2.17 | −1.77 | 2.07 |
53.52 | 56.00 ± 2.52 | 4.63 | 4.50 | 47.39 ± 2.61 | −0.96 | 4.86 | |
0.42 | 0.41 ± 0.01 | −2.79 | 2.81 | 0.42 ± 0.02 | 0.88 | 5.87 | |
Poricoic acid B | 114.70 | 113.56 ± 2.46 | −0.99 | 2.17 | 104.84 ± 4.25 | −0.32 | 2.48 |
57.35 | 56.44 ± 1.24 | −1.59 | 2.20 | 48.90 ± 2.67 | −0.98 | 3.05 | |
0.45 | 0.45 ± 0.02 | −0.40 | 4.41 | 0.45 ± 0.02 | 0.26 | 4.61 | |
Licochalcone A | 107.91 | 104.80 ± 3.22 | −2.88 | 3.08 | 103.65 ± 2.58 | −0.23 | 2.33 |
53.96 | 53.95 ± 2.21 | 1.06 | 3.53 | 48.21 ± 2.24 | 1.21 | 5.36 | |
0.21 | 0.20 ± 0.01 | −3.30 | 2.71 | 0.20 ± 0.01 | 1.61 | 3.63 |
Compound | Concentration Added | Matrix Effect | Extraction Recovery | ||
---|---|---|---|---|---|
(ng/mL) | Mean ± SD (%) | RSD (%) | Mean ± SD (%) | RSD (%) | |
Saikosaponin A | 334.12 | 92.43 ± 3.31 | 3.59 | 90.12 ± 2.48 | 2.75 |
167.06 | 94.11 ± 5.35 | 5.69 | 92.17 ± 4.31 | 4.68 | |
0.53 | 90.93 ± 6.05 | 6.65 | 88.33 ± 6.94 | 7.86 | |
Saikosaponin D | 298.65 | 95.28 ± 4.82 | 5.06 | 91.15 ± 6.00 | 6.58 |
149.32 | 92.86 ± 5.38 | 5.79 | 88.44 ± 4.48 | 5.07 | |
0.48 | 96.43 ± 7.63 | 7.91 | 90.67 ± 6.57 | 7.25 | |
Z-Ligustilide | 99.72 | 91.10 ± 5.95 | 6.53 | 90.07 ± 3.35 | 3.72 |
49.86 | 97.15 ± 4.82 | 4.96 | 92.93 ± 4.39 | 4.73 | |
0.20 | 87.78 ± 6.41 | 7.30 | 93.24 ± 3.07 | 3.30 | |
Levistilide A | 133.65 | 88.60 ± 3.82 | 4.31 | 88.52 ± 3.73 | 4.22 |
66.82 | 97.45 ± 4.89 | 5.02 | 90.58 ± 7.33 | 8.10 | |
0.26 | 94.08 ± 8.04 | 8.55 | 92.43 ± 5.81 | 6.29 | |
Ferulic acid | 275.83 | 95.58 ± 5.90 | 6.18 | 94.51 ± 2.97 | 3.14 |
137.92 | 92.03 ± 7.10 | 7.72 | 91.20 ± 3.98 | 4.36 | |
0.44 | 90.01 ± 6.50 | 7.22 | 89.99 ± 4.23 | 4.70 | |
Liquiritigenin | 99.80 | 94.15 ± 7.07 | 7.51 | 94.04 ± 3.48 | 3.70 |
49.90 | 87.59 ± 4.98 | 5.69 | 87.83 ± 7.88 | 8.97 | |
0.39 | 96.11 ± 4.96 | 4.88 | 90.97 ± 4.30 | 4.73 | |
Liquiritin | 109.96 | 91.46 ± 3.43 | 3.75 | 88.13 ± 7.37 | 8.37 |
54.98 | 101.24 ± 4.44 | 4.39 | 92.31 ± 4.86 | 5.27 | |
0.22 | 98.45 ± 6.07 | 6.17 | 90.99 ± 3.16 | 3.47 | |
Paeoniflorin | 231.77 | 93.78 ± 5.31 | 5.66 | 93.15 ± 6.20 | 6.65 |
115.89 | 94.40 ± 6.66 | 7.06 | 89.84 ± 5.46 | 6.08 | |
0.37 | 91.78 ± 6.73 | 7.34 | 102.23 ± 8.76 | 8.57 | |
Albiflorin | 236.90 | 93.91 ± 5.66 | 6.02 | 91.87 ± 4.18 | 4.54 |
118.45 | 92.65 ± 3.65 | 3.93 | 88.66 ± 4.16 | 4.70 | |
0.37 | 89.92 ± 5.60 | 6.23 | 93.31 ± 3.22 | 3.45 | |
Oxypaeoniflorin | 110.40 | 94.84 ± 4.28 | 4.51 | 93.85 ± 2.92 | 3.12 |
55.20 | 93.51 ± 7.92 | 8.47 | 89.35 ± 5.93 | 6.64 | |
0.44 | 89.59 ± 5.92 | 6.61 | 90.80 ± 7.28 | 8.01 | |
Poricoic acid A | 107.04 | 100.13 ± 3.67 | 3.67 | 94.65 ± 3.58 | 3.78 |
53.52 | 91.97 ± 4.20 | 4.57 | 86.48 ± 4.09 | 4.73 | |
0.42 | 89.52 ± 4.07 | 4.55 | 92.88 ± 4.48 | 4.82 | |
Poricoic acid B | 114.70 | 88.84 ± 5.55 | 6.18 | 87.96 ± 4.64 | 5.27 |
57.35 | 100.83 ± 2.96 | 2.94 | 89.46 ± 4.66 | 5.21 | |
0.45 | 94.04 ± 3.90 | 4.15 | 90.74 ± 5.53 | 6.10 | |
Licochalcone A | 107.91 | 94.24 ± 5.22 | 5.54 | 93.04 ± 5.80 | 6.23 |
53.96 | 99.05 ± 5.16 | 5.21 | 94.65 ± 1.15 | 1.22 | |
0.21 | 97.01 ± 4.95 | 5.10 | 90.59 ± 6.99 | 7.71 |
Compound | Concentration | Short-Term Stability | Long-Term Stability | Freeze–Thaw Stability | |||
---|---|---|---|---|---|---|---|
Mean ± SD | RSD | Mean ± SD | RSD | Mean ± SD | RSD | ||
ng/mL | ng/mL | % | ng/mL | % | ng/mL | % | |
Saikosaponin A | 334.12 | 333.79 ± 5.23 | 1.57 | 333.87 ± 8.64 | 2.59 | 329.84 ± 6.72 | 2.04 |
167.06 | 163.03 ± 6.85 | 4.20 | 157.57 ± 7.50 | 4.76 | 162.70 ± 2.48 | 1.52 | |
0.53 | 0.52 ± 0.02 | 4.10 | 0.53 ± 0.02 | 4.42 | 0.54 ± 0.02 | 3.10 | |
Saikosaponin D | 298.65 | 292.71 ± 9.07 | 3.10 | 286.73 ± 7.86 | 2.74 | 297.24 ± 6.14 | 2.06 |
149.32 | 149.80 ± 6.27 | 4.19 | 144.97 ± 6.67 | 4.60 | 148.89 ± 2.57 | 1.72 | |
0.48 | 0.49 ± 0.03 | 6.27 | 0.48 ± 0.02 | 4.53 | 0.47 ± 0.02 | 4.53 | |
Z-Ligustilide | 99.72 | 98.66 ± 3.18 | 3.22 | 95.84 ± 3.73 | 3.89 | 94.19 ± 7.09 | 7.53 |
49.86 | 49.75 ± 2.30 | 4.62 | 45.73 ± 2.98 | 6.53 | 45.33 ± 5.63 | 12.42 | |
0.20 | 0.20 ± 0.01 | 6.98 | 0.20 ± 0.01 | 5.86 | 0.18 ± 0.02 | 12.39 | |
Levistilide A | 133.65 | 130.75 ± 10.35 | 7.92 | 121.87 ± 2.34 | 1.92 | 134.59 ± 5.82 | 4.32 |
66.82 | 66.05 ± 2.50 | 3.78 | 60.04 ± 2.90 | 4.84 | 59.51 ± 3.13 | 5.26 | |
0.26 | 0.24 ± 0.02 | 6.59 | 0.23 ± 0.01 | 4.83 | 0.24 ± 0.01 | 5.53 | |
Ferulic acid | 275.83 | 270.59 ± 11.52 | 4.25 | 273.01 ± 7.25 | 2.65 | 267.03 ± 12.54 | 4.69 |
137.92 | 135.24 ± 2.82 | 2.08 | 130.44 ± 5.80 | 4.45 | 130.24 ± 5.58 | 4.29 | |
0.44 | 0.46 ± 0.02 | 3.30 | 0.40 ± 0.02 | 5.72 | 0.38 ± 0.02 | 5.72 | |
Liquiritigenin | 109.96 | 109.52 ± 5.78 | 5.28 | 100.24 ± 4.19 | 4.18 | 103.39 ± 4.89 | 4.73 |
54.98 | 54.93 ± 2.87 | 5.22 | 52.98 ± 2.55 | 4.82 | 52.83 ± 2.92 | 5.53 | |
0.22 | 0.21 ± 0.02 | 7.80 | 0.21 ± 0.01 | 4.29 | 0.23 ± 0.01 | 3.28 | |
Liquiritin | 99.80 | 96.45 ± 2.60 | 2.69 | 95.60 ± 3.67 | 3.84 | 95.10 ± 3.05 | 3.20 |
49.90 | 48.26 ± 3.11 | 6.44 | 47.24 ± 1.59 | 3.37 | 48.52 ± 1.78 | 3.67 | |
0.39 | 0.37 ± 0.02 | 5.06 | 0.40 ± 0.01 | 3.60 | 0.40 ± 0.01 | 3.67 | |
Paeoniflorin | 237.77 | 237.17 ± 6.60 | 2.78 | 231.08 ± 10.05 | 4.35 | 230.52 ± 6.66 | 2.89 |
115.89 | 111.05 ± 5.21 | 4.74 | 112.57 ± 4.52 | 4.01 | 111.74 ± 4.34 | 3.89 | |
0.37 | 0.37 ± 0.02 | 5.22 | 0.35 ± 0.01 | 2.67 | 0.33 ± 0.01 | 3.00 | |
Albiflorin | 236.90 | 230.34 ± 9.76 | 4.24 | 234.12 ± 5.07 | 2.17 | 225.62 ± 4.52 | 2.00 |
118.45 | 115.59 ± 4.47 | 3.87 | 1140.07 ± 4.96 | 4.35 | 113.38 ± 3.35 | 2.95 | |
0.37 | 0.37 ± 0.02 | 5.65 | 0.35 ± 0.01 | 3.57 | 0.35 ± 0.02 | 5.27 | |
Oxypaeoniflorin | 110.40 | 106.80 ± 3.52 | 3.30 | 108.06 ± 4.11 | 3.80 | 105.05 ± 2.64 | 2.52 |
55.20 | 54.62 ± 1.43 | 2.62 | 52.95 ± 1.78 | 3.37 | 53.32 ± 2.50 | 4.68 | |
0.44 | 0.43 ± 0.02 | 3.61 | 0.42 ± 0.02 | 4.77 | 0.44 ± 0.03 | 6.27 | |
Poricoic acid A | 107.04 | 107.66 ± 3.53 | 3.28 | 107.10 ± 3.59 | 3.35 | 105.14 ± 1.60 | 1.52 |
53.52 | 51.71 ± 1.40 | 2.72 | 51.89 ± 1.82 | 3.50 | 51.34 ± 1.91 | 3.72 | |
0.42 | 0.42 ± 0.02 | 4.50 | 0.38 ± 0.02 | 5.18 | 0.44 ± 0.02 | 5.57 | |
Poricoic acid B | 114.70 | 113.41 ± 4.31 | 3.80 | 111.42 ± 2.38 | 2.13 | 109.52 ± 3.94 | 3.60 |
57.35 | 53.19 ± 4.00 | 7.52 | 53.53 ± 2.25 | 4.21 | 52.46 ± 1.27 | 2.43 | |
0.45 | 0.43 ± 0.03 | 6.80 | 0.42 ± 0.02 | 4.70 | 0.44 ± 0.03 | 7.34 | |
Licochalcone A | 107.91 | 107.24 ± 2.63 | 2.46 | 105.15 ± 2.91 | 2.77 | 105.15 ± 2.91 | 2.77 |
53.96 | 53.79 ± 0.97 | 1.81 | 52.17 ± 3.64 | 6.97 | 50.15 ± 1.82 | 3.62 | |
0.21 | 0.21 ± 0.01 | 4.17 | 0.20 ± 0.01 | 5.35 | 0.21 ± 0.01 | 5.77 |
Compound | Low Dose | Medium Dose | High Dose |
---|---|---|---|
μg/kg/d | μg/kg/d | μg/kg/d | |
Saikosaponin A | 877.72 | 1775.44 | 3550.88 |
Saikosaponin D | 557.39 | 1114.78 | 2229.56 |
Z-Ligustilide | 904.50 | 1809.00 | 3618.00 |
Levistilide A | 62.96 | 125.92 | 251.84 |
Ferulic acid | 28.73 | 57.46 | 114.92 |
Liquiritigenin | 16.31 | 32.62 | 65.24 |
Liquiritin | 163.40 | 326.80 | 653.60 |
Paeoniflorin | 2080.62 | 4161.24 | 8322.48 |
Albiflorin | 1994.65 | 3989.30 | 7978.60 |
Oxypaeoniflorin | 61.78 | 123.56 | 247.12 |
Poricoic acid A | 23.65 | 47.30 | 94.60 |
Poricoic acid B | 11.34 | 22.68 | 45.36 |
Licochalcone A | 5.29 | 10.58 | 21.16 |
Compound | Precursor Ion | Daughter Ion | Collision Voltage | RT (min) | ESI |
---|---|---|---|---|---|
Saikosaponin A | 779.41 | 144.88 | 45 | 10.89 | - |
Saikosaponin D | 779.43 | 439.13 | 65 | 12.36 | - |
Z-Ligustilide | 190.98 | 76.88 | 40 | 15.75 | + |
Levistilide A | 381.11 | 78.88 | 47 | 15.76 | + |
Ferulic acid | 192.96 | 133.96 | 15 | 7.44 | - |
Liquiritigenin | 254.98 | 90.80 | 27 | 8.78 | - |
Liquiritin | 416.98 | 118.88 | 45 | 6.96 | - |
Paeoniflorin | 479.01 | 120.88 | 20 | 7.87 | - |
Albiflorin | 479.01 | 76.88 | 42 | 6.48 | - |
Oxypaeoniflorin | 495.05 | 136.88 | 29 | 5.17 | - |
Poricoic acid A | 497.30 | 211.05 | 43 | 14.83 | - |
Poricoic acid B | 483.31 | 409.13 | 30 | 14.27 | - |
Licochalcone A | 339.03 | 92.88 | 44 | 12.47 | + |
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Liu, X.; Wan, Y.; Sun, S.; Wang, T.; Li, T.; Sun, Q.; Zhang, W.; Zhao, D.; Tian, Y.; Feng, S. Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS. Molecules 2024, 29, 1230. https://doi.org/10.3390/molecules29061230
Liu X, Wan Y, Sun S, Wang T, Li T, Sun Q, Zhang W, Zhao D, Tian Y, Feng S. Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS. Molecules. 2024; 29(6):1230. https://doi.org/10.3390/molecules29061230
Chicago/Turabian StyleLiu, Xuefang, Yan Wan, Shuding Sun, Ting Wang, Ting Li, Qi Sun, Weiwei Zhang, Di Zhao, Yange Tian, and Suxiang Feng. 2024. "Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS" Molecules 29, no. 6: 1230. https://doi.org/10.3390/molecules29061230
APA StyleLiu, X., Wan, Y., Sun, S., Wang, T., Li, T., Sun, Q., Zhang, W., Zhao, D., Tian, Y., & Feng, S. (2024). Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS. Molecules, 29(6), 1230. https://doi.org/10.3390/molecules29061230