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Abstract:

The corresponding o-aminobenzophenones are usually reported as the main degradation products in the hydrolysis of 1,4-benzodiazepinones. Nevertheless, in previous studies of diazepam (DZ) in acidic aqueous medium we isolated and characterized seven unexpected degradation products. Kinetic measurements under several reaction conditions shed some light on the mechanisms of the complex reactions that are taking place, and photochemical studies give hints on the mechanisms of chlorination and annelation processes. Alprazolam (AL) seems to exhibit an unusually high stability against hydrolysis under several conditions; nevertheless, the structure is sensitive to photolytic cleavage. The photodegradation of AL was studied in aqueous and methanolic solutions. Characterization of the isolated products by 1H and 13C NMR and mass spectrometry revealed that electron transfer, oxidation and rearrangement reactions take place. The influence of several variables such as pH, solvent composition and light irradiation were examined and mechanisms for the formation of three photoproducts are proposed. A specific method for the determination of AL in the presence of photoproducts was developed, which allowed kinetic determinations of the photostability of AL. The photosensitivity observed in some patients treated with AL seems to be due to one of the characterized photoproducts. Copyright © 2004 John Wiley & Sons, Ltd.

Registro:

Documento: Artículo
Título:Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
Autor:Cabrera, C.G.; Goldberg De Waisbaum, R.; Nudelman, N.S.
Filiación:Depto. de Quím. Orgán., Fac. de Ciencias Exactas y Naturales, Ciudad Universitaria, Pab. II, P. 3, 1428 Buenos Aires, Argentina
Palabras clave:Alprazolam; Anxiolytics; Benzodiazepinone pharmaceuticals; Diazepam; Drug stability; Hydrolysis; Photosensitivity; Photostability; Electron transitions; Mass spectrometry; Nuclear magnetic resonance spectroscopy; Oxidation; pH effects; Photodegradation; Photosensitivity; Reaction kinetics; Alprazolam; Anxiolytics; Benzodiazepinone pharmaceuticals; Diazepam; Drug stability; Photostability; Hydrolysis
Año:2005
Volumen:18
Número:2
Página de inicio:156
Página de fin:161
DOI: http://dx.doi.org/10.1002/poc.861
Título revista:Journal of Physical Organic Chemistry
Título revista abreviado:J Phys Org Chem
ISSN:08943230
CODEN:JPOCE
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08943230_v18_n2_p156_Cabrera

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Citas:

---------- APA ----------
Cabrera, C.G., Goldberg De Waisbaum, R. & Nudelman, N.S. (2005) . Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam. Journal of Physical Organic Chemistry, 18(2), 156-161.
http://dx.doi.org/10.1002/poc.861
---------- CHICAGO ----------
Cabrera, C.G., Goldberg De Waisbaum, R., Nudelman, N.S. "Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam" . Journal of Physical Organic Chemistry 18, no. 2 (2005) : 156-161.
http://dx.doi.org/10.1002/poc.861
---------- MLA ----------
Cabrera, C.G., Goldberg De Waisbaum, R., Nudelman, N.S. "Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam" . Journal of Physical Organic Chemistry, vol. 18, no. 2, 2005, pp. 156-161.
http://dx.doi.org/10.1002/poc.861
---------- VANCOUVER ----------
Cabrera, C.G., Goldberg De Waisbaum, R., Nudelman, N.S. Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam. J Phys Org Chem. 2005;18(2):156-161.
http://dx.doi.org/10.1002/poc.861