From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors
Abstract
:1. Introduction
2. Results
2.1. Determination of trans-Lobeline Content
2.1.1. Optimized HPLC Conditions Were Feasible
2.1.2. Determination of trans-Lobeline Percentage Content
2.2. Effects of Two Isomers on Stimulation of Respiratory Are Significantly Different
2.3. Method Validation in the Experiment on Influencing Factors of Isomerization
2.3.1. Selectivity and Specificity
2.3.2. Linearity and LLOQ
2.3.3. Precision and Accuracy
2.3.4. Extraction Recovery
2.3.5. Stability
2.4. Influencing Factors of Isomerization
2.4.1. Temperature Is the Catalytic Factor of Isomerization
2.4.2. pH Is the Key Factor of Isomerization
3. Materials and Methods
3.1. Drugs and Reagents
3.2. Animals, Animal Management, and Experimental Design
3.3. Determination of cis-Lobeline and trans-Lobeline Content
3.4. Method Validation
3.5. Pharmacodynamic Study of trans-Lobeline Isomer
3.6. Study on the Influencing Factors of Isomerization
3.6.1. Investigation of the Relationship between Temperature and Isomerization
3.6.2. Investigation of the Relationship between pH and Isomerization
3.7. Statistical Analysis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Sample Name | cis-Lobeline (%) | trans-Lobeline (%) | Degree of Isomerization (%) |
---|---|---|---|
Fresh | 100% | 0 | 0 |
105 °C 15 min | 61.3 ± 0.45% | 36.9 ± 0.68% | 38.7% |
121 °C 120 min | 32.3 ± 0.47% | 22.5 ± 1.05% | 67.7% |
Sample Name | Degree of Isomerization (%) | Increased Respiratory Rate (bpm) |
---|---|---|
Fresh | 0 | 22.7 ± 4.14 |
105 °C 15 min | 38.7% | 11.3 ± 2.21 *** |
121 °C 120 min | 67.7% | 8.4 ± 1.07 ***, ## |
Name | Standard Curves | R2 | Linear Range (μg/mL) | LLOQ (μg/mL) |
---|---|---|---|---|
cis-lobeline | y = 21.426x − 8.0696 | 0.9998 | 30–240 | 0.36 |
Name | QC Conc. (μg/mL) | Intraday | Interday | ||||
---|---|---|---|---|---|---|---|
Calc Conc. (μg/mL) | RSD (%) | Accuracy (%) | Calc Conc. (μg/mL) | RSD (%) | Accuracy (%) | ||
cis-lobeline | 60.52 | 60.08 ± 2.13 | 0.27 | 99.67 ± 0.28 | 61.03 ± 1.96 | 0.38 | 99.15 ± 1.06 |
121.48 | 120.61 ± 3.27 | 0.50 | 98.79 ± 1.02 | 120.57 ± 2.69 | 0.50 | 98.76 ± 0.94 | |
242.55 | 245.37 ± 4.95 | 0.69 | 97.34 ± 2.06 | 240 ± 3.54 | 0.63 | 96.25 ± 3.21 |
Group | Sample Intake (mg) | Reference Material Added (mg) | Content Determination (mg) | Recovery (%) | Average (%) | RSD (%) |
---|---|---|---|---|---|---|
80% | 2.122 | 1.960 | 4.016 | 98.37 | 98.38 | 0.51 |
2.122 | 1.960 | 3.997 | 97.89 | |||
2.122 | 1.960 | 4.037 | 98.89 | |||
100% | 2.653 | 2.450 | 5.119 | 100.31 | 100.51 | 0.61 |
2.653 | 2.450 | 5.165 | 101.20 | |||
2.653 | 2.450 | 5.105 | 100.03 | |||
120% | 3.184 | 2.941 | 6.138 | 100.23 | 100.27 | 0.42 |
3.184 | 2.941 | 6.117 | 99.88 | |||
3.184 | 2.941 | 6.168 | 100.71 |
Sample Name | cis-Lobeline (%) | trans-Lobeline (%) | Degree of Isomerization (%) |
---|---|---|---|
Fresh | 100 | 0 | 0 |
4 °C 60 days | 99.2 ± 0.39 | 0.6 ± 0.08 | 0.8 |
40 °C 60 days | 93.2 ± 0.63 | 6.7 ± 0.49 | 6.8 |
105 °C 15 min | 61.3 ± 0.45 | 36.9 ± 0.68 | 38.7 |
121 °C 120 min | 32.3 ± 0.47 | 22.5 ± 1.05 | 67.7 |
pH | Hydrogen Ion Concentration (μmol/L) | Degree of Isomerization (%) |
---|---|---|
1.97 | 10,715.2 | 3.084 |
2.04 | 9120.1 | 4.04 |
2.18 | 6606.9 | 4.629 |
2.32 | 4786.3 | 6.316 |
2.64 | 2290.9 | 10.237 |
2.87 | 1349.0 | 12.132 |
2.97 | 1071.5 | 13.537 |
3.1 | 794.3 | 16.236 |
3.24 | 575.4 | 21.66 |
3.43 | 371.5 | 26.61 |
3.63 | 234.4 | 27.134 |
3.9 | 125.9 | 34.796 |
4.27 | 53.7 | 45.824 |
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Xu, H.-H.; Yang, L.; Tang, M.-X.; Ye, A.-P.; Tu, B.-D.; Jiang, Z.-H.; Yi, J.-F. From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors. Molecules 2022, 27, 6253. https://doi.org/10.3390/molecules27196253
Xu H-H, Yang L, Tang M-X, Ye A-P, Tu B-D, Jiang Z-H, Yi J-F. From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors. Molecules. 2022; 27(19):6253. https://doi.org/10.3390/molecules27196253
Chicago/Turabian StyleXu, Huan-Hua, Liang Yang, Ming-Xia Tang, An-Ping Ye, Bo-Dan Tu, Zhen-Hong Jiang, and Jian-Feng Yi. 2022. "From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors" Molecules 27, no. 19: 6253. https://doi.org/10.3390/molecules27196253