title: Direct determination of N-methyl-2-pyrrolidone metabolites in urine by HPLC-electrospray ionization-MS/MS using deuterium-labeled compounds as internal standard.
abstract: N-methyl-2-pyrrolidone (NMP) has been used in many industries and biological monitoring of NMP exposure is preferred to atmospheric monitoring in occupational health. We developed an analytical method that did not include solid phase extraction (SPE) but utilized deuterium-labeled compounds as internal standard for high-performance liquid chromatography-electrospray ionization-mass spectrometry using a C30 column. Urinary concentrations of NMP and its known metabolites 5-hydoxy-N-methyl-2-pyrrolidone (5-HNMP), N-methyl-succinimide (MSI), and 2-hydroxy-N-methylsuccinimide (2-HMSI) were determined in a single run. The method provided baseline separation of these compounds. Their limits of detection in 10-fold diluted urine were 0.0001, 0.006, 0.008, and 0.03 mg/L, respectively. Linear calibration covered a biological exposure index (BEI) for urinary concentration. The within-run and total precisions (CV, %) were 5.6% and 9.2% for NMP, 3.4% and 4.2% for 5-HNMP, 3.7% and 6.0% for MSI, and 6.5% and 6.9% for 2-HMSI. The method was evaluated using international external quality assessment samples, and urine samples from workers exposed to NMP in an occupational area.
authors.affiliation: Research Center for Occupational Poisoning, Tokyo Rosai Hospital, Japan Labour Health and Welfare Organization, 4-13-21, Ohmori-Minami, Ohta-ku, Tokyo 143-0013, Japan. suzy@tokyoh.rofuku.go.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo
authors.forename: Masanori
authors.initials: M
authors.lastname: Ogawa
authors.forename: Shinobu
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Akito
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Onda
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D003903:Deuterium / Q000737:chemistry*; D006801:Humans; D011760:Pyrrolidinones / Q000378:metabolism* / Q000652:urine*; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: D011760:Pyrrolidinones; D003903:Deuterium; C038678:N-methylpyrrolidone