Document Detail


Advanced oxidation chemistry of paracetamol. UV/H(2)O(2)-induced hydroxylation/degradation pathways and (15)N-aided inventory of nitrogenous breakdown products.
MedLine Citation:
PMID:  12182655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The advanced oxidation chemistry of the antipyretic drug paracetamol (1) with the UV/H(2)O(2) system was investigated by an integrated methodology based on (15)N-labeling and GC-MS, HPLC, and 2D (1)H, (13)C, and (15)N NMR analysis. Main degradation pathways derived from three hydroxylation steps, leading to 1,4-hydroquinone/1,4-benzoquinone, 4-acetylaminocatechol and, to a much lesser extent, 4-acetylaminoresorcine. Oxidation of the primary aromatic intermediates, viz. 4-acetylaminocatechol, 1,4-hydroquinone, 1,4-benzoquinone, and 1,2,4-benzenetriol, resulted in a series of nitrogenous and non-nitrogenous degradation products. The former included N-acetylglyoxylamide, acetylaminomalonic acid, acetylaminohydroxymalonic acid, acetylaminomaleic acid, diastereoisomeric 2-acetylamino-3-hydroxybutanedioic acids, 2-acetylaminobutenedioic acid, 3-acetylamino-4-hydroxy-2-pentenedioic acid, and 2,4-dihydroxy-3-acetylamino-2-pentenedioic acid, as well as two muconic and hydroxymuconic acid derivatives. (15)N NMR spectra revealed the accumulation since the early stages of substantial amounts of acetamide and oxalic acid monoamide. These results provide the first insight into the advanced oxidation chemistry of a 4-aminophenol derivative by the UV/H(2)O(2) system, and highlight the investigative potential of integrated GC-MS/NMR methodologies based on (15)N-labeling to track degradation pathways of nitrogenous species.
Authors:
Davide Vogna; Raffaele Marotta; Alessandra Napolitano; Marco D'Ischia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of organic chemistry     Volume:  67     ISSN:  0022-3263     ISO Abbreviation:  J. Org. Chem.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-16     Completed Date:  2003-03-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985193R     Medline TA:  J Org Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6143-51     Citation Subset:  IM    
Affiliation:
Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Via Cinthia 4, I-80126 Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acetaminophen / chemistry*,  radiation effects
Analgesics, Non-Narcotic / chemistry*,  radiation effects
Benzoquinones / chemistry
Chemistry, Organic / methods
Chromatography, High Pressure Liquid
Gas Chromatography-Mass Spectrometry
Hydrogen Peroxide / diagnostic use
Hydroxylation
Magnetic Resonance Spectroscopy
Molecular Structure
Nitrogen / chemistry*
Nitrogen Isotopes / chemistry,  diagnostic use
Oxidation-Reduction
Stereoisomerism
Ultraviolet Rays / diagnostic use
Chemical
Reg. No./Substance:
0/Analgesics, Non-Narcotic; 0/Benzoquinones; 0/Nitrogen Isotopes; 103-90-2/Acetaminophen; 106-51-4/benzoquinone; 7722-84-1/Hydrogen Peroxide; 7727-37-9/Nitrogen

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