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Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution
SY0916 has been proven to be a potent treatment agent against rheumatoid arthritis in preclinical studies and has been shown to be safe in phase I clinical trials. However, SY0916 is unstable in water, which is frequently used in pharmaceutical development processes. The degradation behaviour and st...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350595/ https://www.ncbi.nlm.nih.gov/pubmed/30766739 http://dx.doi.org/10.1155/2019/8789470 |
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author | Jin, Bo Wang, Yanan Zhang, Tingting Yin, Wanting Zhang, Dongfeng Huang, Haihong Ma, Chen |
author_facet | Jin, Bo Wang, Yanan Zhang, Tingting Yin, Wanting Zhang, Dongfeng Huang, Haihong Ma, Chen |
author_sort | Jin, Bo |
collection | PubMed |
description | SY0916 has been proven to be a potent treatment agent against rheumatoid arthritis in preclinical studies and has been shown to be safe in phase I clinical trials. However, SY0916 is unstable in water, which is frequently used in pharmaceutical development processes. The degradation behaviour and stability of SY0916 in aqueous solutions were investigated at different pH levels, periods of time, and temperatures. Two degradation products (DPs) were successfully separated and characterized by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS), liquid chromatography coupled to nuclear magnetic resonance with solid phase extraction (LC-SPE-NMR), and nuclear magnetic resonance (NMR). SY0916 decomposed to its α,β-unsaturated ketone in protonic solvents, and the α,β-unsaturated ketone further transformed into its alcohol form through a conjugate addition reaction in aqueous media. The results of this study indicate that the pH of the buffer solutions should be maintained between 3.0 and 3.6 for maximum SY0916 stability. Factors that affect degradation should be carefully controlled to mitigate or avoid drug decay. |
format | Online Article Text |
id | pubmed-6350595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-63505952019-02-14 Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution Jin, Bo Wang, Yanan Zhang, Tingting Yin, Wanting Zhang, Dongfeng Huang, Haihong Ma, Chen J Anal Methods Chem Research Article SY0916 has been proven to be a potent treatment agent against rheumatoid arthritis in preclinical studies and has been shown to be safe in phase I clinical trials. However, SY0916 is unstable in water, which is frequently used in pharmaceutical development processes. The degradation behaviour and stability of SY0916 in aqueous solutions were investigated at different pH levels, periods of time, and temperatures. Two degradation products (DPs) were successfully separated and characterized by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS), liquid chromatography coupled to nuclear magnetic resonance with solid phase extraction (LC-SPE-NMR), and nuclear magnetic resonance (NMR). SY0916 decomposed to its α,β-unsaturated ketone in protonic solvents, and the α,β-unsaturated ketone further transformed into its alcohol form through a conjugate addition reaction in aqueous media. The results of this study indicate that the pH of the buffer solutions should be maintained between 3.0 and 3.6 for maximum SY0916 stability. Factors that affect degradation should be carefully controlled to mitigate or avoid drug decay. Hindawi 2019-01-14 /pmc/articles/PMC6350595/ /pubmed/30766739 http://dx.doi.org/10.1155/2019/8789470 Text en Copyright © 2019 Bo Jin et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Jin, Bo Wang, Yanan Zhang, Tingting Yin, Wanting Zhang, Dongfeng Huang, Haihong Ma, Chen Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution |
title | Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution |
title_full | Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution |
title_fullStr | Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution |
title_full_unstemmed | Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution |
title_short | Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution |
title_sort | degradation characteristics of a novel paf receptor antagonist, sy0916, in aqueous solution |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350595/ https://www.ncbi.nlm.nih.gov/pubmed/30766739 http://dx.doi.org/10.1155/2019/8789470 |
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