Artículo
Thermally induced solid-state transformation of cimetidine. A multi-spectroscopic/chemometrics determination of the kinetics of the process and structural elucidation of one of the products as a stable N3-enamino tautomer
Calvo, Natalia Lorena
; Simonetti, Sebastián Osvaldo
; Maggio, Ruben Mariano
; Kaufman, Teodoro Saul
Fecha de publicación:
05/2015
Editorial:
Elsevier Science
Revista:
Analytica Chimica Acta
ISSN:
0003-2670
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Exposure of cimetidine (CIM) to dry heat (160-180 °C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics.One of the products was structurally characterized by mono- and bi-dimensional NMR experiments. It was found to be the N3-enamino tautomer (TAU) of CIM, resulting from the thermal isomerization of the double bond of the cyanoguanidine moiety of the drug, from the imine form to its N3-enamine state.The thus generated tautomer demonstrated to be stable for months in the glassy solid and in methanolic solutions. A theoretical study of CIM and TAU revealed that the latter is less stable; however, the energy barrier for tautomer interconversion is high enough, precluding the process to proceed rapidly at room temperature.
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Articulos(IQUIR)
Articulos de INST.DE QUIMICA ROSARIO
Articulos de INST.DE QUIMICA ROSARIO
Citación
Calvo, Natalia Lorena; Simonetti, Sebastián Osvaldo; Maggio, Ruben Mariano; Kaufman, Teodoro Saul; Thermally induced solid-state transformation of cimetidine. A multi-spectroscopic/chemometrics determination of the kinetics of the process and structural elucidation of one of the products as a stable N3-enamino tautomer; Elsevier Science; Analytica Chimica Acta; 875; 5-2015; 22-32
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