Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics
Abstract
:1. Introduction
2. Results and Discussion
2.1. HLM Biotransformation of Nebivolol
2.2. Chemometric Analysis
2.3. Metabolite Identification
2.4. Hepatic Biotransformation Pathways
2.5. In Silico Assessment of Toxicity
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. In Vitro Simulation of Metabolism by HLM
3.3. Analytical Procedures
3.4. Chemometric and Toxicity Prediction Software
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Name | Reaction Type | Retention Time (min) | Measured Mass (m/z) | Theoretical Mass (m/z) | Mass Error (ppm) | Molecular Formula [M + H]+ |
---|---|---|---|---|---|---|
NEB | – | 6.05 | 406.1831 | 406.1824 | 1.72 | C22H26F2NO4 |
M1 | Al-OH | 4.84 | 422.1761 | 422.1774 | 3.07 | C22H26F2NO5 |
M2 | Al-OH | 4.57 | 422.1785 | 422.1774 | 2.61 | C22H26F2NO5 |
M3 | Ar-OH | 5.58 | 422.1761 | 422.1774 | 3.08 | C22H26F2NO5 |
M4 | Al-OH, Deh | 5.30 | 420.1618 | 420.1617 | 0.24 | C22H24F2NO5 |
M5 | Al-OH | 3.45 | 438.1726 | 438.1723 | 0.68 | C22H26F2NO6 |
M6 | N-dealk | 2.08 | 212.1083 | 212.1081 | 0.94 | C11H15FNO2 |
Toxicity Model | NEB | M6 | M1 | M2 | M3 | M4 | M5 |
---|---|---|---|---|---|---|---|
Mouse IP | 2.34 | 2.88 | 2.45 | 2.42 | 2.4 | 2.36 | 2.45 |
Mouse OR | 2.59 | 2.68 | 2.68 | 2.65 | 2.67 | 2.81 | 2.87 |
Mouse IV | 1.72 | 2.04 | 1.73 | 1.83 | 1.78 | 1.8 | 1.75 |
Mouse SC | 3.32 | 2.84 | 3.45 | 3.38 | 3.36 | 3.3 | 3.53 |
Rat IP | 1.70 | 2.54 | 1.76 | 1.85 | 1.84 | 1.93 | 1.81 |
Rat OR | 2.83 | 2.76 | 2.88 | 2.86 | 3.01 | 2.8 | 2.96 |
Rat OR T.E.S.T. | 3.15 | 2.64 | 3.06 | 3.4 | 2.67 | 3.01 | 2.77 |
Ames Percepta | 0.06 | 0.61 | 0.08 | 0.06 | 0.05 | 0.07 | 0.08 |
Ames T.E.S.T. | 0.10 | 0.45 | 0.46 | 0.21 | 0.5 | 0.56 | 0.46 |
Developmental Toxicity | 0.62 | 0.76 | 0.71 | 0.57 | 0.81 | 0.75 | 0.65 |
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Trawiński, J.; Wroński, M.; Gawlik, M.; Skibiński, R. Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics. Molecules 2022, 27, 763. https://doi.org/10.3390/molecules27030763
Trawiński J, Wroński M, Gawlik M, Skibiński R. Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics. Molecules. 2022; 27(3):763. https://doi.org/10.3390/molecules27030763
Chicago/Turabian StyleTrawiński, Jakub, Michał Wroński, Maciej Gawlik, and Robert Skibiński. 2022. "Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics" Molecules 27, no. 3: 763. https://doi.org/10.3390/molecules27030763