Abstract
The aim was to study the metabolic pathway forN-methyl-2-pyrrolidone (NMP) in humans. Three healthy male volunteers were administered 100 mg NMP orally. All urine was collected during nine consecutive days. The identification and quantification of the metabolites were performed by gas chromatography/mass spectrometry (GC/MS). NMP, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP),N-methylsuccinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) were found in urine. The mean excreted fractions for NMP, 5-HNMP, MSI, and 2-HMSI were 0.8%, 44%, 0.4%, and 20%, respectively. There was no conjugation with glucoronic acid or sulfate or either 5-HNMP or 2-HMSI. One-third of the orally dosed NMP was not recovered in urine as either NMP, 5-HNMP, MSI, or 2-HMSI. The half-lives for 5-HNMP, MSI, and 2-HMSI in urine were approximateley 4, 8, and 17 hr, respectively.
Footnotes
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Received April 25, 1996; accepted November 8, 1996.
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This study was supported by the Swedish Council for Work Life Research and the Medical Faculty of Lund University.
- Abbreviations used are::
- NMP
- N-methyl-2-pyrrolidone
- 5-HNMP
- 5-hydroxy-N-methyl-2-pyrrolidone
- 2H4-5-HNMP
- tetradeuterium-labeledN-methyl-2-pyrrolidone
- 2H4-MSI
- tetradeuterium-labeled-N-methylsuccinimide
- 2H3-2-HMSI
- trideuterium-labeled 2-hydroxy-N-methylsuccinimide
- MSI
- N-methylsuccinimide
- 2-HMSI
- 2-hydroxy-N-methylsuccinimide
- EI
- electron impact
- IS
- internal standard
- CO
- carbon monoxide
- 3-HNMP
- 3-hydroxy-N-methyl-2-pyrrolidone
- The American Society for Pharmacology and Experimental Therapeutics
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