title: Simultaneous determination of N-hydroxymethyl-N-methylformamide, N-methylformamide and N-acetyl-S-(N-methylcarbamoyl)cystein in urine samples from workers exposed to N,N-dimethylformamide by liquid chromatography-tandem mass spectrometry.
abstract: N-Hydroxymethyl-N-methylformamide (HMMF) and N-methylformamide (NMF) in urine samples from workers exposed to N,N-dimethylformamide (DMF) cannot be distinguished by a gas chromatographic method because HMMF is converted to NMF at the injection port of gas chromatography (GC). Total NMF (HMMF+NMF) has been measured instead. Also, the determination of N-acetyl-S-(N-methylcarbamoyl)cystein (AMCC), which is supposed to be related to the toxicity of DMF, needs multiple treatments to convert to a volatile compound before GC analysis. There is no previous report of a simultaneous determination of three major metabolites of DMF in urine. The aim of this study is to develop a simple and selective method for the determination of DMF metabolite in urine. By using a liquid chromatography-tandem mass spectrometry, we can directly distinguish these three major metabolites of DMF in a single run. The diluted urine samples were analyzed on Capcell Pak MF SG80 column with the mobile phase of methanol in 2mM formic acid (10:90, v/v). The analytes were detected by an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. The standard curves were linear (r>0.999) over the concentration ranges of 0.004-8 microg/mL. The precision and accuracy of quality control samples for inter-batch (n=6) analyses were in the range of 1.3-9.8% and 94.7-116.8, respectively. The sum of each HMMF and NMF concentration determined by LC-MS/MS method shows high correlation (r=0.9927 with the slope of 1.0415, p<0.0001) with NMF included HMMF concentration determined by GC method for 13 urine samples taken from workers exposed to DMF. The excretion ratio of HMMF:NMF:AMCC is approximately 4:1:1 in molar concentration.
authors.affiliation: Phillips Exeter Academy, Exeter, NH 03833-2460, USA.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Sohn
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Han
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Kang
authors.forename: Jeong Sun
authors.initials: JS
authors.lastname: Yang
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods; D004126:Dimethylformamide / Q000032:analysis* / Q000378:metabolism; D004785:Environmental Pollutants / Q000652:urine*; D005559:Formamides / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D016273:Occupational Exposure / Q000032:analysis*
chemical_list: D004785:Environmental Pollutants; D005559:Formamides; C052469:N-acetyl-S-(N-methylcarbamoyl)cysteine; D004126:Dimethylformamide; D000111:Acetylcysteine; C002950:methylformamide