Identification of metabolites of [1,2,3-13C]propargyl alcohol in rat urine by 13C NMR and mass spectrometry

Abstract

Little is known about the metabolism of acetylenic (CC) 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.