Identification of the major degradation pathways of ticagrelor
Ticagrelor is a direct-acting and reversible P2Y12-adenosine diphosphate (ADP) receptor blocker used as antiplatelet drug. Forced degradation under various stress conditions was carried out. The degradation products have been detected and identified by high-pressure liquid chromatography multistage mass spectrometry (LC-MS(n)) along with high-resolution mass spectrometry. C18 XTerra MS column combined with a linear gradient mobile phase composed of a mixture of 10 mM acetate ammonium/acetonitrile was shown suitable for drug and impurity determinations and validated as a stability indicating method. Structural elucidation of the degradation products relied on MS(n) studies and accurate mass measurements giving access to elemental compositions. Up to nine degradation products resulting from oxidation/auto-oxidation, S-dealkylation and N-dealkylation have been identified, covering a range of possible degradation pathways for derivatives with such functional groups. Kinetics was also studied in order to assess the molecule's shelf-life and to identify the most important degradation factors..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
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| Enthalten in: |
Journal of pharmaceutical and biomedical analysis - 105(2015), Seite 74-83 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sadou Yaye, Hassane [VerfasserIn] |
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| Links: |
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| doi: |
10.1016/j.jpba.2014.11.046 |
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| 245 | 1 | 0 | |a Identification of the major degradation pathways of ticagrelor |
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| 520 | |a Ticagrelor is a direct-acting and reversible P2Y12-adenosine diphosphate (ADP) receptor blocker used as antiplatelet drug. Forced degradation under various stress conditions was carried out. The degradation products have been detected and identified by high-pressure liquid chromatography multistage mass spectrometry (LC-MS(n)) along with high-resolution mass spectrometry. C18 XTerra MS column combined with a linear gradient mobile phase composed of a mixture of 10 mM acetate ammonium/acetonitrile was shown suitable for drug and impurity determinations and validated as a stability indicating method. Structural elucidation of the degradation products relied on MS(n) studies and accurate mass measurements giving access to elemental compositions. Up to nine degradation products resulting from oxidation/auto-oxidation, S-dealkylation and N-dealkylation have been identified, covering a range of possible degradation pathways for derivatives with such functional groups. Kinetics was also studied in order to assess the molecule's shelf-life and to identify the most important degradation factors. | ||
| 540 | |a Nutzungsrecht: Copyright © 2014 Elsevier B.V. All rights reserved. | ||
| 650 | 4 | |a Chromatography, Reverse-Phase - methods | |
| 650 | 4 | |a Adenosine - analogs & derivatives | |
| 650 | 4 | |a Purinergic P2Y Receptor Antagonists - chemistry | |
| 650 | 4 | |a Mass Spectrometry - methods | |
| 650 | 4 | |a Purinergic P2Y Receptor Antagonists - analysis | |
| 650 | 4 | |a Chromatography, Reverse-Phase - instrumentation | |
| 650 | 4 | |a Platelet Aggregation Inhibitors - analysis | |
| 650 | 4 | |a Platelet Aggregation Inhibitors - chemistry | |
| 650 | 4 | |a Adenosine - radiation effects | |
| 650 | 4 | |a Purinergic P2Y Receptor Antagonists - radiation effects | |
| 650 | 4 | |a Adenosine - analysis | |
| 650 | 4 | |a Adenosine - chemistry | |
| 650 | 4 | |a Platelet Aggregation Inhibitors - radiation effects | |
| 700 | 1 | |a Secrétan, Philippe-Henri |4 oth | |
| 700 | 1 | |a Henriet, Théo |4 oth | |
| 700 | 1 | |a Bernard, Mélisande |4 oth | |
| 700 | 1 | |a Amrani, Fatma |4 oth | |
| 700 | 1 | |a Akrout, Wiem |4 oth | |
| 700 | 1 | |a Tilleul, Patrick |4 oth | |
| 700 | 1 | |a Yagoubi, Najet |4 oth | |
| 700 | 1 | |a Do, Bernard |4 oth | |
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| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/25543285 |
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