Major metabolic pathway for N-methyl-2-pyrrolidone in humans

The aim was to study the metabolic pathway for N-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 approximately 4, 8, and 17 hr, respectively.