Advanced oxidation chemistry of paracetamol. UV/H(2)O(2)-induced hydroxylation/degradation pathways and (15)N-aided inventory of nitrogenous breakdown products.
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.
Vogna
Davide
D
Department of Organic Chemistry and Biochemistry, University of Naples Federico II, Via Cinthia 4, I-80126 Naples, Italy.
Marotta
Raffaele
R
Napolitano
Alessandra
A
D'Ischia
Marco
M
D000082:Acetaminophen / Q000737:chemistry* / Q000528:radiation effects; D018712:Analgesics, Non-Narcotic / Q000737:chemistry* / Q000528:radiation effects; D016227:Benzoquinones / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006861:Hydrogen Peroxide; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D009587:Nitrogen Isotopes / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014466:Ultraviolet Rays
D018712:Analgesics, Non-Narcotic; D016227:Benzoquinones; D009587:Nitrogen Isotopes; D000082:Acetaminophen; C004532:quinone; D006861:Hydrogen Peroxide; D009584:Nitrogen