Identification of Metabolites of [1,2,3-13C]Propargyl Alcohol in Rat Urine by 13C NMR and Mass Spectrometry

Little is known about the metabolism of acetylenic (C⋮C) compounds commonly used in the formulation of pesticides. To better understand the in vivo reactivity of this bond, we examined the metabolism of propargyl alcohol (PA), 2-propyn-1-ol, used extensively in the chemical industry. [1,2,3-13C, 2,3...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 1999-04, Vol.47 (4), p.1717-1729
Main Authors: Banijamali, Ali R, Xu, Yaodong, Strunk, Richard J, Gay, Michael H, Ellis, Michael C, Putterman, Gerald J, Sumner, Susan J
Format: Article
Language:English
Subjects:
alcohols
Biological and medical sciences
carbon
chemical reactions
chemical structure
Food industries
Food toxicology
Fundamental and applied biological sciences. Psychology
glutathione
identification
mass spectrometry
Medical sciences
metabolic detoxification
metabolism
metabolites
nuclear magnetic resonance spectroscopy
oral administration
oxidation
Pesticides, fertilizers and other agrochemicals toxicology
rats
stable isotopes
Toxicology
urine
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Summary:Little is known about the metabolism of acetylenic (C⋮C) compounds commonly used in the formulation of pesticides. To better understand the in vivo reactivity of this bond, we examined the metabolism of propargyl alcohol (PA), 2-propyn-1-ol, used extensively in the chemical industry. [1,2,3-13C, 2,3-14C]PA was administered orally to male Sprague−Dawley rats. Approximately 56% of the dose was excreted in urine by 96 h. Major metabolites were characterized, directly, in the whole urine by one- and two-dimensional 13C NMR. To determine the complete structures of metabolites of PA, rat urine was also subjected to TLC followed by purification of separated TLC bands on HPLC. The purified metabolites were identified by 13C NMR and mass spectrometry and by comparison with available synthetic standards. The proposed metabolic pathway involves oxidation of propargyl alcohol to 2-propynoic acid and further detoxification via glutathione conjugation to yield as final products:  3,3-bis[(2-(acetylamino)-2-carboxyethyl)thio]-1-propanol, 3-(carboxymethylthio)-2-propenoic acid, 3-(methylsulfinyl)-2-(methylthio)-2-propenoic acid, 3-[[2-(acetylamino)-2-carboxyethyl]thio]-3-[(2-amino-2-carboxyethyl)thio]-1-propanol and 3-[[2-(acetylamino)-2-carboxyethyl]sulfinyl]-3-[2-(acetylamino)-2-carboxyethyl]thio]-1-propanol. These unique metabolites have not been reported previously and represent the first example of multiple glutathione additions to the carbon−carbon triple bond. Keywords: Propargyl alcohol metabolism; metabolism of carbon−carbon triple bond; dicysteinyl conjugates; 2-propyn-1-ol
ISSN:0021-8561
1520-5118
DOI:10.1021/jf980870o