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Biomed Chromatogr ; 33(6): e4496, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30663135

RESUMO

The purpose of this paper is to describe the glycosylation of ambrisentan (AMB) by cultures of Cunninghamella elegans ATCC 9245. AMB is an endothelin receptor antagonist, which is used to treat pulmonary arterial hypertension. Filamentous fungi are morphologically complex and may exhibit different forms depending on the species and the nature of the culture medium. A biotransformation study was conducted to investigate the ability of C. elegans to metabolize AMB. Parameters were optimized by testing on different culture media and concentrations, pH, drug concentration, static and shaking conditions. Ambrisentan's metabolite, obtained after 240 h of incubation as a result of glycosylation pathway, was separated by HPLC and determined by high-resolution mass spectrometry. The method showed linearity over 300-1000 µg mL-1 (r = 0.998). Accuracy, precision, robustness and stability studies agree with international guidelines. Results are consistent in accordance with the principles of green chemistry as the experimental conditions had a low environmental impact, and used little solvent.


Assuntos
Cunninghamella/metabolismo , Glicosídeos/análise , Glicosídeos/metabolismo , Fenilpropionatos/análise , Fenilpropionatos/metabolismo , Piridazinas/análise , Piridazinas/metabolismo , Biotransformação , Técnicas de Cultura de Células , Cromatografia Líquida de Alta Pressão , Glicosídeos/química , Espectrometria de Massas , Fenilpropionatos/química , Piridazinas/química
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