Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam

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 measuremen...

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Detalles Bibliográficos
Autor principal: Goldberg de Waisbaum, Raquel Nora
Publicado: 2005
Materias:
Alprazolam
Anxiolytics
Benzodiazepinone pharmaceuticals
Diazepam
Drug stability
Hydrolysis
Photosensitivity
Photostability
Electron transitions
Mass spectrometry
Nuclear magnetic resonance spectroscopy
Oxidation
pH effects
Photodegradation
Reaction kinetics
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08943230_v18_n2_p156_Cabrera
http://hdl.handle.net/20.500.12110/paper_08943230_v18_n2_p156_Cabrera
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id paper:paper_08943230_v18_n2_p156_Cabrera
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spelling paper:paper_08943230_v18_n2_p156_Cabrera2023-06-08T15:47:43Z Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam Goldberg de Waisbaum, Raquel Nora 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 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. Fil:Goldberg De Waisbaum, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08943230_v18_n2_p156_Cabrera http://hdl.handle.net/20.500.12110/paper_08943230_v18_n2_p156_Cabrera
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic 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
spellingShingle 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
Goldberg de Waisbaum, Raquel Nora
Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
topic_facet 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
description 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.
author Goldberg de Waisbaum, Raquel Nora
author_facet Goldberg de Waisbaum, Raquel Nora
author_sort Goldberg de Waisbaum, Raquel Nora
title Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
title_short Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
title_full Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
title_fullStr Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
title_full_unstemmed Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
title_sort kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
publishDate 2005
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08943230_v18_n2_p156_Cabrera
http://hdl.handle.net/20.500.12110/paper_08943230_v18_n2_p156_Cabrera
work_keys_str_mv AT goldbergdewaisbaumraquelnora kineticandmechanisticstudiesonthehydrolysisandphotodegradationofdiazepamandalprazolam
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