Photodegradation of novel oral anticoagulants under sunlight irradiation in aqueous matrices
Montaha Yassine1, Laura Fuster2, Marie-Hélène Dévier2
1Univ. Bordeaux, UMR EPOC CNRS 5805, LPTC, F-33405, Talence, France; CNRS, EPOC, UMR 5805, LPTC, F-33400, Talence, France; National Council of Scientific Research (NCSR), Lebanese Atomic Energy Commission (LAEC), Laboratory of Analysis of Organic Pollutants (LAOP), B. P. 11-8281, Riad El Solh, 1107 2260, Beirut, Lebanon.
Abstract:
Kinetics of photodegradation of novel oral anticoagulants dabigatran, rivaroxaban, and apixaban were studied under simulated solar light irradiation in purified, mineral, and river waters. Dabigatran and rivaroxaban underwent direct photolysis with polychromatic quantum yields of 2.2 × 10-4 and 4.4 × 10-2, respectively. The direct photodegradation of apixaban was not observed after 19 h of irradiation. Kinetics of degradation of rivaroxaban was not impacted by the nature of the aqueous matrix while photosensitization from nitrate ions was observed for dabigatran and apixaban dissolved in a mineral water. The photosensitized reactions were limited in the tested river water (Isle River, Périgueux, France) certainly due to the hydroxyl radical scavenging effect of the dissolved organic matter. The study of photoproduct structures allowed to identify two compounds for dabigatran. One of them is the 4-aminobenzamidine while the second one is a cyclization product. In the case of rivaroxaban, as studied by very high field NMR, only one photoproduct was observed i.e. a photoisomer. Finally, seven photoproducts were clearly identified from the degradation of apixaban under simulated solar light.
Insights
Photodegradation kinetics of novel oral anticoagulants (NOACs) dabigatran, rivaroxaban, and apixaban were investigated. Rivaroxaban degraded directly, while dabigatran and apixaban showed photosensitization, with varying photoproducts identified.
Area of Science:
- Environmental Chemistry
- Photochemistry
- Pharmaceutical Science
Background:
- Novel oral anticoagulants (NOACs) like dabigatran, rivaroxaban, and apixaban are increasingly used.
- Understanding their environmental fate, particularly photodegradation, is crucial for risk assessment.
Purpose of the Study:
- To investigate the photodegradation kinetics and pathways of dabigatran, rivaroxaban, and apixaban.
- To assess the influence of water matrices (purified, mineral, river) on NOAC photodegradation.
- To identify photodegradation products of these pharmaceuticals.
Main Methods:
- Simulated solar light irradiation experiments were conducted in different water types.
- Direct photolysis and photosensitization reactions were analyzed.
- Photoproducts were identified using techniques like very high field NMR.
Main Results:
- Dabigatran and rivaroxaban underwent direct photolysis; apixaban did not show direct photodegradation.
- Photosensitization by nitrate ions was observed for dabigatran and apixaban in mineral water.
- Dissolved organic matter in river water limited photosensitized reactions.
- Specific photoproducts were identified for dabigatran (4-aminobenzamidine, cyclization product), rivaroxaban (photoisomer), and apixaban (seven products).
Conclusions:
- The photodegradation of NOACs is influenced by water composition and light exposure.
- Rivaroxaban exhibits relatively stable photodegradation, while dabigatran and apixaban pathways are more complex.
- Further research is needed to fully elucidate the environmental impact and transformation of these widely used anticoagulants.
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