Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study
Abstract
:1. Introduction
2. Experimental
2.1. Chemicals and Reagents
2.2. HPLC–MS/MS Instrumentation and Chromatography Conditions
2.3. Preparation of Calibration Standard and Quality Control (QC) Samples
2.4. Sample Preparation
2.5. Method Validation
2.5.1. Selectivity and Specificity
2.5.2. Linearity and Lower Limits of Quantification (LLOQ)
2.5.3. Precision and Accuracy
2.5.4. Extraction Recovery and Matrix Effect
2.5.5. Stability Experiment and Dilution Integrity
2.6. Pharmacokinetic Study
2.7. Date Analysis
3. Results and Discussion
3.1. Method Development
3.1.1. Optimization of HPLC–MS/MS Conditions
3.1.2. Optimization of Sample Preparation
3.2. Method Validation
3.2.1. Specificity and Selectivity
3.2.2. Linearity and Sensitivity
3.2.3. Precision and Accuracy
3.2.4. Extraction Recovery and Matrix Effect
3.2.5. Stability and Dilution Integrity
3.3. Pharmacokinetic Study
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: The extracts of Corydalis yanhusuo are available from the authors. |
No. | Alkaloids | Ret. Time (min) | MRM Transition Precursor Ion > Product Ion | Fragmentor Voltage (V) | Collision Energy (eV) |
---|---|---|---|---|---|
1 | Corydaline | 3.67 | 370.2 > 192.1 | 150 | 27 |
2 | Tetrahydroberberine | 3.54 | 340.2 > 176.1 | 150 | 27 |
3 | Tetrahydropalmatine | 3.00 | 356.2 > 192.1 | 150 | 29 |
4 | Tetrahydrocolumbamine | 2.08 | 342.1 > 178.1 | 150 | 27 |
5 | Tetrahydrocoptisine | 3.19 | 324.1 > 176.2 | 150 | 24 |
6 | Columbamine | 2.90 | 338.1 > 322.1 | 150 | 27 |
7 | Palmatine | 4.04 | 352.3 > 336.2 | 150 | 30 |
8 | Berberine | 4.21 | 336.1 > 320.1 | 150 | 30 |
9 | Epiberberine | 2.98 | 336.1 > 320.1 | 150 | 30 |
10 | Coptisine | 3.12 | 320.0 > 292.1 | 150 | 30 |
11 | Jatrorrhizine | 3.04 | 338.1 > 322.1 | 150 | 27 |
12 | Dehydrocorydaline | 4.49 | 366.1 > 350.1 | 150 | 30 |
13 | Oxoglaucine | 4.89 | 352.3 > 306.0 | 150 | 28 |
14 | Protopine | 2.58 | 354.2 > 188.0 | 150 | 30 |
IS | Nitidine chloride | 4.43 | 348.1 > 332.0 | 210 | 35 |
No. | Alkaloids | Linear Regression Equation | Range (ng/mL) | Correlation Coeffiicient (r) | LLOQ (ng/mL) |
---|---|---|---|---|---|
1 | Corydaline | Y = 0.139805χ − 0.006704 | 0.74–73.89 | 0.998 | 0.74 |
2 | Tetrahydroberberine | Y = 0.097085χ − 0.004676 | 0.68–67.88 | 0.998 | 0.68 |
3 | Tetrahydropalmatine | Y = 0.301153χ + 0.199059 | 1.78–177.7 | 0.996 | 1.78 |
4 | Tetrahydrocolumbamine | Y = 0.216374χ − 0.021908 | 1.71–170.7 | 0.998 | 1.71 |
5 | Tetrahydrocoptisine | Y = 0.177838χ − 0.044206 | 1.62–161.7 | 0.997 | 1.62 |
6 | Columbamine | Y = 0.089586χ + 0.011028 | 0.68–67.68 | 0.999 | 0.68 |
7 | Palmatine | Y = 0.120359χ + 0.052267 | 0.71–70.48 | 0.998 | 0.71 |
8 | Berberine | Y = 0.125996χ + 0.005547 | 0.67–67.27 | 0.999 | 0.67 |
9 | Epiberberine | Y = 0.072013χ − 0.003910 | 0.67–67.27 | 0.999 | 0.67 |
10 | Coptisine | Y = 0.007792χ + 0.11179 | 3.20–320.3 | 0.998 | 3.20 |
11 | Jatrorrhizine | Y = 0.085938χ − 0.008861 | 0.68–67.68 | 0.999 | 0.68 |
12 | Dehydrocorydaline | Y = 0.106311χ + 0.107424 | 1.83–183.2 | 0.998 | 1.83 |
13 | Oxoglaucine | Y = 0.113817χ + 0.031077 | 0.70–70.27 | 0.998 | 0.70 |
14 | Protopine | Y = 0.106329χ + 0.007831 | 0.71–70.67 | 0.999 | 0.71 |
Alkaloids | Nominal Conc. (ng/mL) | Intra-Day Batch (n = 5) | Inter-Day Batch (n = 9) | ||||
---|---|---|---|---|---|---|---|
Observed Conc. (ng/mL) | Precision (%, RSD) | Accuracy (%, RE) | Observed Conc. (ng/mL) | Precision (%, RSD) | Accuracy (%, RE) | ||
Corydaline | 0.74 | 0.73 ± 0.023 | 3.1 | −1.5 | 0.75 ± 0.012 | 1.6 | 1.1 |
1.85 | 1.86 ± 0.096 | 5.2 | 0.5 | 1.82 ± 0.059 | 3.2 | −1.6 | |
9.24 | 9.59 ± 0.21 | 2.2 | 3.8 | 9.39 ± 0.31 | 3.3 | 1.6 | |
55.42 | 53.27 ± 1.36 | 2.5 | −3.9 | 55.9 ± 2.01 | 3.6 | 0.9 | |
Tetrahydroberberine | 0.68 | 0.68 ± 0.017 | 2.5 | 0.7 | 0.68 ± 0.019 | 2.9 | −0.6 |
1.70 | 1.72 ± 0.039 | 2.2 | 1.3 | 1.68 ± 0.033 | 2.0 | −1.2 | |
8.48 | 8.82 ± 0.16 | 1.8 | 4.0 | 8.68 ± 0.35 | 4.0 | 2.3 | |
50.91 | 48.51 ± 1.18 | 2.4 | −4.7 | 51.32 ± 1.97 | 3.8 | 0.8 | |
Tetrahydropalmatine | 1.78 | 1.78 ± 0.099 | 5.5 | 0.2 | 1.78 ± 0.024 | 1.4 | 0.2 |
3.55 | 3.66 ± 0.14 | 3.9 | 3.0 | 3.56 ± 0.09 | 2.5 | 0.2 | |
17.77 | 19.15 ± 0.28 | 1.5 | 7.7 | 18.7 ± 0.60 | 3.2 | 5.2 | |
142.17 | 129.2 ± 2.92 | 2.3 | −9.2 | 137.2 ± 5.75 | 4.2 | −3.5 | |
Tetrahydrocolumbamine | 1.71 | 1.72 ± 0.038 | 2.2 | 0.9 | 1.72 ± 0.036 | 2.1 | 0.9 |
3.41 | 3.61 ± 0.036 | 1.0 | 5.6 | 3.40 ± 0.14 | 4.0 | −0.3 | |
17.07 | 17.11 ± 0.83 | 4.8 | 0.3 | 17.34 ± 0.27 | 1.6 | 1.6 | |
136.6 | 133.1 ± 2.52 | 1.9 | −2.5 | 134.1 ± 6.47 | 4.8 | −1.8 | |
Tetrahydrocoptisine | 1.62 | 1.48 ± 0.050 | 3.4 | −8.8 | 1.59 ± 0.067 | 4.2 | −1.6 |
3.23 | 3.42 ± 0.12 | 3.5 | 5.6 | 3.16 ± 0.11 | 3.5 | −2.2 | |
16.17 | 15.74 ± 0.98 | 6.2 | −2.6 | 16.33 ± 0.31 | 1.9 | 1.0 | |
129.3 | 130.4 ± 3.11 | 2.4 | 0.8 | 127.7 ± 5.12 | 4.0 | −1.3 | |
Columbamine | 0.68 | 0.65 ± 0.011 | 1.6 | −4.1 | 0.67 ± 0.013 | 2.0 | −0.4 |
1.69 | 1.75 ± 0.056 | 3.2 | 3.5 | 1.66 ± 0.043 | 2.6 | −1.7 | |
8.46 | 8.89 ± 0.25 | 2.8 | 5.0 | 8.76 ± 0.41 | 4.6 | 3.6 | |
50.76 | 49.29 ± 1.59 | 3.2 | −2.9 | 51.63 ± 1.95 | 3.8 | 1.7 | |
Palmatine | 0.70 | 0.69 ± 0.032 | −1.9 | 4.6 | 0.71 ± 0.015 | 2.1 | 0.4 |
1.76 | 1.90 ± 0.16 | 8.2 | 7.9 | 1.78 ± 0.059 | 3.3 | 0.9 | |
8.81 | 9.26 ± 0.20 | 2.1 | 5.2 | 8.95 ± 0.22 | 2.5 | 1.6 | |
52.86 | 50.70 ± 1.36 | 2.7 | −4.1 | 52.6 ± 1.50 | 2.8 | −0.5 | |
Berberine | 0.67 | 0.67 ± 0.014 | 2.1 | −0.3 | 0.68 ± 0.013 | 2.0 | 0.6 |
1.68 | 1.78 ± 0.12 | 6.9 | 5.9 | 1.68 ± 0.027 | 1.6 | 0.1 | |
8.41 | 8.77 ± 0.25 | 2.9 | 4.2 | 8.62 ± 0.24 | 2.8 | 2.5 | |
50.45 | 48.34 ± 1.20 | 2.5 | −4.2 | 50.23 ± 1.30 | 2.6 | −0.4 | |
Epiberberine | 0.67 | 0.68 ± 0.036 | 5.3 | 1.1 | 0.69 ± 0.022 | 3.2 | 2.3 |
1.68 | 1.71 ± 0.088 | 5.2 | 1.9 | 1.66 ± 0.051 | 3.0 | −1.0 | |
8.41 | 8.86 ± 0.19 | 2.1 | 5.3 | 8.57 ± 0.26 | 3.0 | 2.0 | |
50.45 | 48.76 ± 1.49 | 3.1 | −3.4 | 50.19 ± 1.31 | 2.6 | −0.5 | |
Coptisine | 3.20 | 2.83 ± 0.18 | 6.5 | −11.5 | 3.16 ± 0.18 | 5.7 | −1.5 |
6.41 | 6.87 ± 0.87 | 12.6 | 7.3 | 6.35 ± 0.31 | 4.8 | −0.9 | |
32.03 | 35.58 ± 3.82 | 10.7 | 11.1 | 30.97 ± 0.99 | 3.2 | −3.3 | |
256.3 | 254.7 ± 15.00 | 5.9 | −0.6 | 256.9 ± 7.23 | 2.8 | 0.2 | |
Jatrorrhizine | 0.68 | 0.69 ± 0.021 | 3.1 | 1.6 | 0.70 ± 0.015 | 2.2 | 3.6 |
1.69 | 1.79 ± 0.045 | 2.5 | 5.9 | 1.65 ± 0.058 | 3.5 | −2.3 | |
8.46 | 8.73 ± 0.33 | 3.8 | 3.2 | 8.54 ± 0.14 | 1.6 | 0.9 | |
50.76 | 48.82 ± 1.48 | 3.0 | −3.8 | 51.03 ± 3.41 | 6.7 | 0.5 | |
Dehydrocorydaline | 1.83 | 1.76 ± 0.23 | 12.9 | −3.8 | 1.78 ± 0.11 | 6.4 | −2.8 |
3.66 | 3.85 ± 0.27 | 6.9 | 5.0 | 3.65 ± 0.12 | 3.3 | −0.4 | |
18.32 | 17.28 ± 1.39 | 8.0 | −5.7 | 18.16 ± 0.34 | 1.9 | −0.9 | |
146.6 | 144.5 ± 5.45 | 3.8 | −1.4 | 144.1 ± 2.86 | 2.0 | −1.7 | |
Oxoglaucine | 0.70 | 0.66 ± 0.045 | 6.8 | −5.5 | 0.69 ± 0.039 | 5.6 | −1.5 |
1.76 | 1.82 ± 0.075 | 4.1 | 3.6 | 1.75 ± 0.021 | 1.2 | −0.1 | |
8.78 | 9.57 ± 0.20 | 2.1 | 9.0 | 9.13 ± 0.26 | 2.9 | 3.9 | |
52.7 | 50.76 ± 1.52 | 3.0 | −3.7 | 52.83 ± 1.29 | 2.4 | 0.2 | |
Protopine | 0.71 | 0.68 ± 0.019 | 2.7 | −3.5 | 0.71 ± 0.013 | 1.9 | 0.9 |
1.77 | 1.80 ± 0.050 | 2.8 | 1.7 | 1.77 ± 0.042 | 2.4 | 0.3 | |
8.83 | 9.34 ± 0.16 | 1.7 | 5.8 | 9.16 ± 0.32 | 3.5 | 3.7 | |
53.01 | 51.00 ± 1.40 | 2.7 | −3.8 | 53.36 ± 1.94 | 3.6 | 0.7 |
Alkaloids | Conc. (ng/mL) | Recovery (%) | Absolute Matrix Effect (%) | ||
---|---|---|---|---|---|
(Mean ± SD, n = 5) | RSD | (Mean ± SD, n = 6) | RSD | ||
Corydaline (1) | 1.85 | 93.73 ± 3.12 | 3.3 | 102.5 ± 1.55 | 1.5 |
9.24 | 92.12 ± 3.30 | 3.6 | 102.2 ± 2.39 | 2.3 | |
55.42 | 92.57 ± 2.48 | 2.7 | 98.28 ± 2.45 | 2.5 | |
Tetrahydroberberine (2) | 1.70 | 95.83 ± 2.19 | 2.3 | 103.0 ± 2.13 | 2.1 |
8.48 | 92.39 ± 3.56 | 3.8 | 100.5 ± 2.24 | 2.2 | |
50.91 | 93.16 ± 2.8 | 3.0 | 96.40 ± 2.95 | 3.1 | |
Tetrahydropalmatine (3) | 3.55 | 94.18 ± 2.37 | 2.5 | 106.6 ± 2.32 | 2.2 |
17.77 | 91.74 ± 2.77 | 3.0 | 103.8 ± 2.38 | 2.3 | |
142.2 | 108.0 ± 1.97 | 1.8 | 100.4 ± 2.79 | 2.8 | |
Tetrahydrocolumbamine (4) | 3.41 | 83.00 ± 2.55 | 3.1 | 106.5 ± 2.08 | 2.0 |
17.07 | 86.30 ± 1.53 | 1.8 | 106.1 ± 1.80 | 1.7 | |
136.6 | 86.38 ± 1.94 | 2.2 | 110.6 ± 2.86 | 2.6 | |
Tetrahydrocoptisine (5) | 3.23 | 71.73 ± 2.77 | 3.9 | 104.2 ± 4.21 | 4.0 |
16.17 | 76.32 ± 1.15 | 1.5 | 102.3 ± 1.18 | 1.2 | |
129.3 | 80.90 ± 4.08 | 5.0 | 102.4 ± 4.96 | 4.8 | |
Columbamine (6) | 1.69 | 96.77 ± 5.95 | 6.2 | 105.7 ± 2.78 | 2.6 |
8.46 | 91.23 ± 3.15 | 3.5 | 101.7 ± 2.85 | 2.8 | |
50.76 | 92.41 ± 2.55 | 2.8 | 98.07 ± 2.64 | 2.7 | |
Palmatine (7) | 1.76 | 95.88 ± 8.92 | 9.3 | 108.0 ± 3.28 | 3.0 |
8.81 | 86.52 ± 3.24 | 3.8 | 102.6 ± 2.46 | 2.4 | |
52.86 | 89.90 ± 2.30 | 2.6 | 99.70 ± 2.84 | 2.8 | |
Berberine (8) | 1.68 | 97.73 ± 7.28 | 7.4 | 102.2 ± 2.28 | 2.2 |
8.41 | 88.21 ± 4.34 | 4.9 | 101.6 ± 2.48 | 2.4 | |
50.45 | 90.29 ± 2.58 | 2.9 | 97.93 ± 2.83 | 2.9 | |
Epiberberine (9) | 1.68 | 90.67 ± 3.96 | 4.4 | 105.3 ± 3.61 | 3.4 |
8.41 | 88.14 ± 3.61 | 4.1 | 101.7 ± 2.09 | 2.0 | |
50.45 | 90.49 ± 3.22 | 3.6 | 97.60 ± 2.82 | 2.9 | |
Coptisine (10) | 6.41 | 96.83 ± 10.61 | 11.0 | 107.5 ± 5.78 | 5.4 |
32.03 | 93.39 ± 9.84 | 10.5 | 101.9 ± 1.74 | 1.7 | |
256.3 | 92.03 ± 5.11 | 5.6 | 97.06 ± 2.91 | 3.0 | |
Jatrorrhizine (11) | 1.69 | 76.38 ± 2.83 | 3.7 | 108.9 ± 2.66 | 2.4 |
8.46 | 82.54 ± 1.49 | 1.8 | 104.6 ± 1.56 | 1.5 | |
50.76 | 72.26 ± 2.30 | 3.2 | 108.0 ± 3.71 | 3.4 | |
Dehydrocorydaline (12) | 3.66 | 83.90 ± 3.45 | 4.1 | 112.4 ± 3.40 | 3.0 |
18.32 | 83.51 ± 5.27 | 6.3 | 110.9 ± 6.39 | 5.8 | |
146.6 | 86.45 ± 3.14 | 3.6 | 109.0 ± 2.40 | 2.2 | |
Oxoglaucine (13) | 1.76 | 111.2 ± 3.08 | 2.8 | 109.6 ± 5.53 | 5.0 |
8.78 | 104.4 ± 2.82 | 2.7 | 115.4 ± 5.97 | 5.2 | |
52.7 | 112.3 ± 4.27 | 3.8 | 108.4 ± 3.23 | 3.0 | |
Protopine (14) | 1.77 | 94.86 ± 3.04 | 3.2 | 105.2 ± 1.11 | 1.1 |
8.83 | 92.52 ± 2.94 | 3.2 | 102.7 ± 2.72 | 2.6 | |
53.01 | 94.86 ± 2.48 | 2.6 | 98.65 ± 2.93 | 3.0 | |
IS | 5.00 | 71.40 ± 2.89 | 4.0 | 99.50 ± 3.11 | 3.1 |
Alkaloids | Spiked Conc. (ng/mL) | Room Temp. for 8 h | Post-Preparation Stability (10 °C) for 12 h | Frozen for 3 Months (−20 °C) | Three-Freeze–Thaw Cycle | ||||
---|---|---|---|---|---|---|---|---|---|
Accuracy (%, RE) | Precision (%, RSD) | Accuracy (%, RE) | Precision (%, RSD) | Accuracy (%, RE) | Precision (%, RSD) | Accuracy (%, RE) | Precision (%, RSD) | ||
Corydaline (1) | 1.85 | −9.8 | 4.9 | −4.1 | 1.0 | 9.6 | 9.3 | −14.0 | 8.7 |
55.42 | −9.4 | 0.4 | 7.7 | 4.5 | −2.2 | 6.6 | −7.0 | 4.3 | |
Tetrahydroberberine (2) | 1.70 | −9.5 | 2.1 | −3.8 | 1.8 | 8.9 | 7.5 | −13.2 | 6.6 |
50.91 | −10.3 | 1.2 | 6.3 | 4.2 | 1.5 | 7.6 | −8.8 | 3.5 | |
Tetrahydropalmatine (3) | 3.55 | −8.8 | 1.8 | −0.1 | 0.8 | 6.2 | 7.0 | −13.1 | 6.8 |
142.2 | −13.6 | 1.3 | 0.5 | 4.0 | −4.1 | 7.6 | 1.8 | 1.6 | |
Tetrahydrocolumbamine (4) | 3.41 | 14.2 | 2.7 | 1.8 | 4.4 | 4.6 | 3.2 | −10.0 | 1.2 |
136.6 | 8.8 | 1.5 | −3.2 | 0.7 | 3.8 | 1.3 | −2.9 | 3.4 | |
Tetrahydrocoptisine (5) | 3.23 | 12.9 | 1.4 | 4.8 | 2.2 | 5.6 | 2.6 | −11.0 | 1.5 |
129.3 | 6.6 | 2.0 | −1.9 | 1.4 | 4.3 | 0.6 | −7.7 | 3.9 | |
Columbamine (6) | 1.69 | −7.9 | 1.9 | 1.2 | 0.8 | −10.7 | 1.0 | −12.2 | 5.5 |
50.76 | −5.6 | 2.2 | 8.5 | 3.3 | 0.7 | 6.5 | −10.4 | 3.2 | |
Palmatine (7) | 1.76 | −14.5 | 3.4 | −4.0 | 2.6 | −4.0 | 5.3 | −8.6 | 8.5 |
52.86 | −8.6 | 3.3 | 5.5 | 3.9 | 3.3 | 5.6 | −12.7 | 3.5 | |
Berberine (8) | 1.68 | 3.8 | 4.3 | 6.5 | 0.3 | 2.3 | 7.0 | −11.7 | 6.2 |
50.45 | −9.0 | 1.5 | 5.3 | 3.6 | 1.7 | 5.0 | −12.1 | 3.9 | |
Epiberberine (9) | 1.68 | −4.4 | 2.8 | −3.2 | 2.4 | 6.5 | 3.7 | −10.7 | 4.3 |
50.45 | −7.6 | 1.5 | 5.6 | 2.7 | 4.4 | 6.5 | −10.4 | 2.9 | |
Coptisine (10) | 6.41 | 4.0 | 3.5 | 3.0 | 0.5 | 10.9 | 5.5 | −12.9 | 5.9 |
256.3 | −6.5 | 1.1 | 6.2 | 4.1 | 3.2 | 6.0 | −11.4 | 4.2 | |
Jatrorrhizine (11) | 1.69 | 11.4 | 6.2 | −1.1 | 3.2 | 2.6 | 7.3 | −3.8 | 2.5 |
50.76 | 11.3 | 12.4 | −4.1 | 0.5 | 7.0 | 1.4 | −15.6 | 3.7 | |
Dehydrocorydaline (12) | 3.66 | 10.6 | 2.6 | −0.8 | 3.2 | 7.2 | 6.0 | −19.0 | 3.3 |
146.6 | 3.4 | 1.0 | −0.2 | 0.4 | 0.6 | 0.8 | −2.7 | 2.8 | |
Oxoglaucine (13) | 1.76 | 10.2 | 3.8 | 0.2 | 1.6 | 8.4 | 3.7 | −6.0 | 8.9 |
52.7 | −6.4 | 1.8 | 0.1 | 2.0 | −4.1 | 1.5 | −13.2 | 0.8 | |
Protopine (14) | 1.77 | −6.5 | 2.6 | 0.7 | 0.5 | 1.4 | 3.2 | −13.1 | 4.6 |
53.01 | −5.8 | 6.3 | 6.5 | 3.9 | 0.5 | 7.1 | −11.1 | 2.5 |
Alkaloids | Spiked Conc. (ng/mL) | Dilution Factor | Measured Conc. (ng/mL) | Accuracy (%, RE) | Precision (%, RSD) |
---|---|---|---|---|---|
Corydaline (1) | 369.45 | 10 | 33.07 ± 1.96 | −10.5 | 5.9 |
20 | 18.16 ± 0.80 | −1.7 | 4.4 | ||
Tetrahydroberberine (2) | 339.38 | 10 | 36.05 ± 1.27 | 6.2 | 3.5 |
20 | 18.27 ± 1.02 | 7.7 | 5.6 | ||
Tetrahydropalmatine (3) | 355.43 | 10 | 38.57 ± 2.32 | 8.5 | 6.0 |
20 | 17.92 ± 0.15 | 0.8 | 0.8 | ||
Tetrahydrocolumbamine (4) | 341.4 | 10 | 34.74 ± 0.66 | 0.0 | 3.7 |
20 | 17.57 ± 0.65 | −1.1 | 1.9 | ||
Tetrahydrocoptisine (5) | 323.34 | 10 | 31.37 ± 1.25 | −3.0 | 3.1 |
20 | 15.67 ± 0.49 | −3.0 | 4.0 | ||
Columbamine (6) | 338.38 | 10 | 34.15 ± 2.06 | 0.9 | 6.0 |
20 | 16.95 ± 0.49 | 0.2 | 2.9 | ||
Palmatine (7) | 352.4 | 10 | 36.54 ± 1.73 | 3.7 | 4.7 |
20 | 19.63 ± 0.17 | 11.4 | 0.8 | ||
Berberine (8) | 336.36 | 10 | 31.44 ± 1.90 | −6.5 | 6.0 |
20 | 14.80 ± 0.70 | −12.0 | 4.8 | ||
Epiberberine (9) | 336.36 | 10 | 34.05 ± 2.08 | 1.2 | 6.1 |
20 | 16.04 ± 0.65 | −4.6 | 4.0 | ||
Coptisine (10) | 1601.6 | 10 | 165.3 ± 6.02 | 3.2 | 3.6 |
20 | 83.42 ± 1.79 | 4.2 | 2.2 | ||
Jatrorrhizine (11) | 338.38 | 10 | 34.33 ± 0.64 | 0.4 | 2.6 |
20 | 16.99 ± 0.45 | 1.4 | 1.9 | ||
Dehydrocorydaline (12) | 366.43 | 10 | 34.71 ± 0.61 | −4.0 | 8.4 |
20 | 17.59 ± 1.48 | −5.3 | 1.7 | ||
Oxoglaucine (13) | 351.35 | 10 | 36.73 ± 1.92 | 4.5 | 5.2 |
20 | 17.53 ± 0.84 | −0.2 | 4.8 | ||
Protopine (14) | 353.37 | 10 | 36.66 ± 2.20 | 3.8 | 6.0 |
20 | 17.39 ± 0.81 | −1.6 | 4.7 |
No. | Parameters | Cmax (ng/mL) | Tmax (min) | AUC0−t (ng min/mL) | AUC0−∞ (ng min/mL) | MRT0−t (min) | T1/2z (min) |
---|---|---|---|---|---|---|---|
1 | Corydaline | 53.27 ± 23.9 | 11.88 ± 2.59 | 4213.67 ± 1053.77 | 4219.32 ± 1052.51 | 115.09 ± 16.58 | 129.76 ± 53.45 |
2 | Tetrahydroberberine | 36.00 ± 23.1 | 10.00 ± 2.67 | 2017.5 ± 625.79 | 2020.81 ± 626 | 86.64 ± 22.68 | 90.31 ± 29.54 |
3 | Tetrahydropalmatine | 196.8 ± 116.3 | 17.50 ± 8.02 | 23,339.78 ± 7008.07 | 23,532.54 ± 7028.61 | 111.04 ± 17.06 | 62.11 ± 28.68 |
4 | Tetrahydrocolumbamine | 29.45 ± 22.39 | 35.63 ± 11.16 | 5330.56 ± 1151.48 | 5629.85 ± 1260.27 | 142.33 ± 9.13 | 94.02 ± 42.89 |
5 | Tetrahydrocoptisine | 65.86 ± 27.11 | 10.63 ± 1.77 | 6399.24 ± 1272.69 | 6402.31 ± 1274.6 | 123.42 ± 17.29 | 82.19 ± 30.62 |
6 | Columbamine | 1.66 ± 1.01 | 10.00 ± 2.67 | 492.33 ± 155.03 | 513.41 ± 155.25 | 327.8 ± 92.90 | 346.25 ± 148.93 |
7 | Palmatine | 14.33 ± 11.83 | 15.00 ± 6.55 | 2122.38 ± 549.93 | 2394.48 ± 518.15 | 169.29 ± 26.40 | 130.94 ± 28.77 |
8 | Berberine | ND * | ND | ND | ND | ND | ND |
9 | Epiberberine | ND | ND | ND | ND | ND | ND |
10 | Coptisine | 18.73 ± 13.31 | 28.13 ± 9.61 | 8039.17 ± 1924.04 | 8917.46 ± 1825.53 | 387.9 ± 90.88 | 432.93 ± 209.37 |
11 | Jatrorrhizine | 1.78 ± 0.57 | 15.63 ± 6.23 | 449.51 ± 160.24 | 461.64 ± 152.08 | 246.78 ± 59.02 | 196.09 ± 90.99 |
12 | Dehydrocorydaline | 8.50 ± 6.57 | 11.88 ± 7.53 | 2185.27 ± 1137.06 | 2222.64 ± 1125.92 | 163.18 ± 77.61 | 90.71 ± 56.48 |
13 | Oxoglaucine | 32.73 ± 21.2 | 15.00 ± 7.07 | 4797.27 ± 329.42 | 4831.29 ± 336.64 | 232.27 ± 33.42 | 202.93 ± 50.20 |
14 | Protopine | 26.43 ± 24.22 | 21.25 ± 9.54 | 3025.95 ± 736.76 | 3075.23 ± 706.99 | 163.5 ± 21.94 | 318.76 ± 251.55 |
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Du, W.; Jin, L.; Li, L.; Wang, W.; Zeng, S.; Jiang, H.; Zhou, H. Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study. Molecules 2018, 23, 714. https://doi.org/10.3390/molecules23040714
Du W, Jin L, Li L, Wang W, Zeng S, Jiang H, Zhou H. Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study. Molecules. 2018; 23(4):714. https://doi.org/10.3390/molecules23040714
Chicago/Turabian StyleDu, Weijuan, Lisha Jin, Liping Li, Wei Wang, Su Zeng, Huidi Jiang, and Hui Zhou. 2018. "Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study" Molecules 23, no. 4: 714. https://doi.org/10.3390/molecules23040714