Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF
Abstract
:1. Introduction
2. Results and Discussion
2.1. Metabolite Identification
2.2. HLM Biotransformation of Dapoxetine
2.3. Hepatic Biotransformation Pathways
2.4. 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. In Silico Assessment of the Toxicity of Dapoxetine and Its Metabolites
4. Conclusions
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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Name | Reaction Type | Retention TIMe (min) | Measured Mass (m/z) | Theoretical Mass (m/z) | Mass Error (ppm) | Molecular Formula ([M + H]+) | MS/MS Fragmentation (m/z) and Formulas ([M + H]+) |
---|---|---|---|---|---|---|---|
DAP | – | 7.55 | 306.1843 | 306.1852 | −2.94 | C21H24NO | 261.1287 (C19H17O); 233.0967 (C17H13O); 215.0877 (C17H11); 183.0809 (C13H11O); 157.0649 (C11H9O); 145.0638 (C10H9O); 129.0697 (C10H7); 117.0698 (C9H9); 91.0544 (C7H7); 77.0396 (C6H5) |
M1 | Dealk | 7.43 | 292.1687 | 292.1696 | −3.08 | C20H22NO | 261.1272 (C19H17O); 243.1159 (C19H15); 233.0955 (C17H13O); 215.0852 (C17H11); 183.0804 (C13H11O); 157.0645 (C11H9O); 145.0638 (C10H9O); 129.0698 (C10H7); 117.0701 (C9H9); 101.0384 (C8H5); 91.0549 (C7H7); 77.0392 (C6H5) |
M2 | Dealk Ar-OH | 5.31 | 308.1634 | 308.1645 | −3.57 | C20H22NO2 | 277.1220 (C19H17O2); 249.0909 (C17H13O2); 231.0830 (C17H11O); 199.0748 (C13H11O2); 173.0597 (C11H9O2); 159.0451 (C10H9O2); 145.0655 (C10H9O); 127.0545 (C10H7); 117.0696 (C9H9); 105.0703 (C8H9); 91.0548 (C7H7) |
M3 | Ar-OH | 5.36 | 322.1770 | 322.1801 | −9.62 | C21H24NO2 | 277.1277 (C19H17O2); 249.0906 (C17H13O2); 199.0749 (C13H11O2); 173.0593 (C11H9O2); 145.0649 (C10H9O); 117.0702 (C9H9) |
M4 | Dearyl Red | 0.75 | 180.1373 | 180.1383 | −5.55 | C11H18NO | 135.0797 (C9H11O); 117.0689 (C9H9); 105.0698 (C8H9); 91.0546 (C7H7) |
M5 | N-ox | 7.86 | 322.1770 | 322.1801 | −9.62 | C21H24NO2 | 261.1271 (C19H17O); 233.0940 (C17H13O); 183.0802 (C13H11O); 157.0638 (C11H9O); 129.0694 (C10H7); 117.0698 (C9H9); 74.0979 (C4H12N); 62.0610 (C2H8NO) |
M6 | Dealk | 7.04 | 278.1528 | 278.1539 | −3.95 | C19H20NO | 261.1263 (C19H17O); 233.0973 (C17H13O); 183.0804 (C13H11O); 157.0646 (C11H9O); 129.0687 (C10H7); 117.0690 (C9H9) |
M7 | Ar-OH | 6.46 | 322.1770 | 322.1801 | −9.62 | C21H24NO2 | 277.1218 (C19H17O2); 199.0774 (C13H11O2); 145.0640 (C10H9O); 117.0704 (C9H9) |
M8 | Dealk Ar-OH | 6.39 | 308.1634 | 308.1645 | −3.57 | C20H22NO2 | 277.1231 (C19H17O2); 145.0640 (C10H9O); 117.0703 (C9H9) |
M9 | Dealk Ar-OH | 4.90 | 294.1479 | 294.1489 | −3.40 | C19H20NO2 | 277.1225 (C19H17O2); 199.0744 (C13H11O2); 173.0583 (C11H9O2); 177.0699 (C9H9) |
M10 | N-ox Ar-OH | 5.62 | 338.1724 | 338.1751 | −7.98 | C21H24NO3 | 277.1218 (C19H17O2); 199.0737 (C13H11O2); 173.0600 (C11H9O2); 117.0698 (C9H9); 62.0615 (C2H8NO) |
M11 | Dearyl | 0.88 | 178.1216 | 178.1226 | −5.61 | C11H16NO | 136.9301 (C9H14N); 117.0709 (C9H9); 105.0710 (C8H9); 91.0551 (C7H7) |
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Skibiński, R.; Trawiński, J.; Gawlik, M. Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF. Molecules 2021, 26, 3794. https://doi.org/10.3390/molecules26133794
Skibiński R, Trawiński J, Gawlik M. Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF. Molecules. 2021; 26(13):3794. https://doi.org/10.3390/molecules26133794
Chicago/Turabian StyleSkibiński, Robert, Jakub Trawiński, and Maciej Gawlik. 2021. "Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF" Molecules 26, no. 13: 3794. https://doi.org/10.3390/molecules26133794