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Determination of the peptide AWRK6 in rat plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and its application to pharmacokinetics
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Jin, Lili, Ding, Haibo, Degirmenci, Volkan, Xin, Hongchuan, Miao, Qifan, Wang, Qiuyu and Zhang, Dianbao (2021) Determination of the peptide AWRK6 in rat plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and its application to pharmacokinetics. Molecules, 27 (1). e92. doi:10.3390/molecules27010092 ISSN 1420-3049.
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WRAP-determination-peptide-AWRK6-rat-plasma-liquid-chromatography-tandem-mass-spectrometry-application-pharmacokinetics-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (820Kb) | Preview |
Official URL: https://doi.org/10.3390/molecules27010092
Abstract
AWRK6 was a synthesized peptide developed based on the natural occurring peptide dybowskin-2CDYa, which was discovered in frog skin in our previous study. Here, a quantitative determination method for AWRK6 analysis in rat plasma by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established and validated following U.S. FDA guidelines. A combination of plasma precipitation and liquid−liquid extraction was applied for the extraction. For pharmacokinetics study, the rats were administrated with AWRK6 via intraperitoneal and intravenous injection. The prepared plasma samples were separated on an ODS column and analyzed by tandem MS using precursor-to-product ion pairs of m/z: 533.4→84.2 for AWRK6 and m/z: 401.9→101.1 for internal standard Polymyxin B sulfate in multiple reaction monitoring mode. AWRK6 concentrations in rat plasma peaked at about 1.2 h after intraperitoneal injections at 2.35, 4.7 and 9.4 mg/kg bodyweight. The terminal half-life was around 2.8 h. The absolute bioavailability of AWRK6 was 50% after 3 doses via injection, and the apparent volume of distribution was 4.884 ± 1.736 L. The obtained determination method and pharmacokinetics profiles of AWRK6 provides a basis for further development, and forms a benchmark reference for peptide quantification.
| Item Type: | Journal Article | |||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering | |||||||||
| SWORD Depositor: | Library Publications Router | |||||||||
| Library of Congress Subject Headings (LCSH): | Peptides, Peptide antibiotics, Pharmacokinetics, Rats | |||||||||
| Journal or Publication Title: | Molecules | |||||||||
| Publisher: | MDPI | |||||||||
| ISSN: | 1420-3049 | |||||||||
| Official Date: | 24 December 2021 | |||||||||
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| Volume: | 27 | |||||||||
| Number: | 1 | |||||||||
| Article Number: | e92 | |||||||||
| DOI: | 10.3390/molecules27010092 | |||||||||
| Status: | Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Date of first compliant deposit: | 27 January 2022 | |||||||||
| Date of first compliant Open Access: | 28 January 2022 | |||||||||
| RIOXX Funder/Project Grant: |
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