Identification of the major degradation pathways of ticagrelor

Yayé, Hassane Sadou; Secrétan, Philippe-Henri; Henriet, Théo; Bernard, Mélisande; Amrani, Fatma; Akrout, Wiem; Tilleul, P.; Yagoubi, Najet; Do, Bernard

doi:10.1016/j.jpba.2014.11.046

Cited by 19 publications

(9 citation statements)

References 8 publications

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“…All our experiments were conducted without any protection from daylight. However, in view of the sensitivity of the five molecules to oxidation, it is thus advocated to protect the mixtures from light, so as to avoid indirect photolysis in the presence of oxygen [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs

et al. 2022

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Background: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered. Methods: The drug mixtures were studied in a pure form or diluted in NaCl 0.9% or G5%. Twenty-six possible combinations of the five drugs were produced in glass vials or polypropylene syringes and stored at 25 °C for 14 days. The LC method was implemented to study drugs combinations in the presence of the degradation products. The clearness and pH were also monitored. Results: All the 26 possible combinations displayed adequate physicochemical stability at 25 °C: at least 3 days and 7 days, respectively, for the dilution in 0.9% NaCl or glucose 5%, and the pure drug products mixtures. Conclusions: The study provided sufficient stability results, covering the medication administration period of at least three days. The combination of more than two drugs offers the advantage of minimizing the individual doses and reduces unwanted side-effects. Hence, this study opens up the possibility of combining the five drugs in one single syringe, which is useful especially under the current circumstances associated with an important shortage of programmable syringe pumps and pharmaceuticals.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs

et al. 2022

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“…The fragmentation pattern of TIC was obtained in a previous publication [14]. Those results will be used to analyse the interaction and degradation products in the present mixture with TIC and ASA.…”

Section: Thermal Stress Testingmentioning

confidence: 90%

“…In our previous study, we have demonstrated that TIC gives rise to the degradation product m/z 371 by N-dealkylation when it is subjected to 80°C in solution [14]. However, the interaction with ASA increased the appearance of this dealkylation productten-fold.…”

Section: Proposed Pathways For the Observed Degradation Products In Tmentioning

confidence: 95%

“…In the case of TIC, a single patent exists describing four polymorphs called I, II, III and IV melting at 128, 135, 139 and 150 °C respectively [13]. Previously, the chemical behaviour of TIC under several stress conditions has been investigated, which resulted in the elucidation of nine main degradation products formed through oxidation, S-dealkylation and N-dealkylation mechanisms [14]. Taking into account the physical and chemical properties of the pure compounds, mixtures of ASA and TIC will be investigated using differential scanning calorimetry (DSC) andliquid chromatography -high resolution -multistage mass spectrometry (LC-HR-MS TIC and ASA substances were dried at 80 °C in an oven for 24 hours, then mixed (1:1molar ratio) by gentle grinding using a mortar and a pestle for 5 minutes.…”

Section: Introductionmentioning

confidence: 99%

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Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies

Yayé

Rietveld

Secrétan

et al. 2017

European Journal of Pharmaceutical Sciences

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“…Degradation products resulted from oxidation/autooxidation, S-dealkylation and N-dealkylation have been identified, covering a large range of possible degradation pathways. Degradation kinetics was studied in order to assess the molecule's shelf-life and to identify the most important degradation factors; TCG proved to be extremely sensitive towards light and oxidative conditions (Yaye et al, 2015).…”

Section: Liquid Chromatography-mass Spectrometrymentioning

confidence: 99%

Analytical methodologies for the determination of ticagrelor

Kelemen

Hancu

Papp

2019

Biomedical Chromatography

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Ticagrelor is an orally administered platelet aggregation inhibitor with a cyclopentyl‐triazolopyrimidine structure; it is a selective reversible P2Y12 receptor antagonist, which prevents P2Y12‐mediated and ADP‐mediated platelet activation and aggregation. It is used to reduce the rate of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome or history of myocardial infarction. Several analytical methods have been published for the determination of ticagrelor in pharmaceuticals and biological materials by spectrophotometry, high‐performance liquid chromatography with ultraviolet detection and liquid chromatography coupled with tandem mass spectrometry. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the determination of ticagrelor since its introduction in therapy until today.

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Identification of the major degradation pathways of ticagrelor

Cited by 19 publications

References 8 publications

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs

Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies

Analytical methodologies for the determination of ticagrelor

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