Identification of the major degradation pathways of ticagrelor
Copyright © 2014 Elsevier B.V. All rights reserved..
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: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2015 |
|---|---|
| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
|---|---|
| Enthalten in: |
Journal of pharmaceutical and biomedical analysis - 105(2015) vom: 12. Feb., Seite 74-83 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sadou Yayé, Hassane [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 30.09.2015 Date Revised 21.02.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jpba.2014.11.046 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM244911266 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM244911266 | ||
| 003 | DE-627 | ||
| 005 | 20231224135722.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jpba.2014.11.046 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0816.xml |
| 035 | |a (DE-627)NLM244911266 | ||
| 035 | |a (NLM)25543285 | ||
| 035 | |a (PII)S0731-7085(14)00590-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sadou Yayé, Hassane |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Identification of the major degradation pathways of ticagrelor |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 30.09.2015 | ||
| 500 | |a Date Revised 21.02.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2014 Elsevier B.V. All rights reserved. | ||
| 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Degradation kinetic | |
| 650 | 4 | |a Degradation pathways | |
| 650 | 4 | |a Electrospray orbitrap mass spectrometry | |
| 650 | 4 | |a LC stability-indicating assay method | |
| 650 | 4 | |a Ticagrelor | |
| 650 | 7 | |a Platelet Aggregation Inhibitors |2 NLM | |
| 650 | 7 | |a Purinergic P2Y Receptor Antagonists |2 NLM | |
| 650 | 7 | |a Ticagrelor |2 NLM | |
| 650 | 7 | |a GLH0314RVC |2 NLM | |
| 650 | 7 | |a Adenosine |2 NLM | |
| 650 | 7 | |a K72T3FS567 |2 NLM | |
| 700 | 1 | |a Secrétan, Philippe-Henri |e verfasserin |4 aut | |
| 700 | 1 | |a Henriet, Théo |e verfasserin |4 aut | |
| 700 | 1 | |a Bernard, Mélisande |e verfasserin |4 aut | |
| 700 | 1 | |a Amrani, Fatma |e verfasserin |4 aut | |
| 700 | 1 | |a Akrout, Wiem |e verfasserin |4 aut | |
| 700 | 1 | |a Tilleul, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Yagoubi, Najet |e verfasserin |4 aut | |
| 700 | 1 | |a Do, Bernard |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of pharmaceutical and biomedical analysis |d 1983 |g 105(2015) vom: 12. Feb., Seite 74-83 |w (DE-627)NLM012641928 |x 1873-264X |7 nnns |
| 773 | 1 | 8 | |g volume:105 |g year:2015 |g day:12 |g month:02 |g pages:74-83 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jpba.2014.11.046 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 105 |j 2015 |b 12 |c 02 |h 74-83 | ||