Analysis of urinary N-acetyl-S-(N-methylcarbamoyl)cysteine, the mercapturic acid derived from N,N-dimethylformamide.
Human biotransformation of the industrial solvent N,N-dimethylformamide gives raise to N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) which has the longest half-life (about 23 h) among urinary metabolites of N,N-dimethylformamide. It could be used for monitoring industrial exposure over several workdays, by measuring it in urine samples collected at the end of the working week. This is consistent with the suggestions of the American Conference of Governmental Industrial Hygienists, which established a limit of 40 mg/l for the year 2000. An easy, cheap and user-friendly method has been developed for determination of urinary AMCC. Unlike currently available methods, it requires neither a time-consuming preparation phase nor gas chromatographic analysis with a nitrogen-phosphorus or mass detector. The method uses high-performance liquid chromatography (HPLC), with an UV detector at 436 nm. A 10-microl volume of urine is added to a carbonate-hydrogen carbonate buffer and mixed with a dabsyl chloride solution in acetonitrile. The reaction between AMCC and the reagent is performed at 70 degrees C for 10 min. The 'dabsylated' product is stable for at least 12 h. After brief centrifugation, the solution is ready for HPLC analysis using a C18 column (250 x 4.6 mm, 5 microm). The method is sensitive (detection limit 1.8 mg/l) and specific. It identified urinary AMCC in urine of 40 subjects not exposed to N,N-dimethylformamide with a median concentration of 3.9 mg/l. In urine samples from 20 workers exposed to N,N-dimethylformamide (5-40.8 mg/m3), AMCC concentrations ranged from 16 to 170 mg/l. Industrial toxicology laboratories with limited instrumentation will be able to use it in the biological monitoring of workers exposed to N,N-dimethylformamide.
Perbellini
L
L
Department of Medicine and Public Health, Policlinico G.B. Rossi, Verona, Italy.
Maestri
L
L
Veronese
N
N
Romani
S
S
Brugnone
F
F
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000652:urine*; D001711:Biotransformation; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004126:Dimethylformamide / Q000493:pharmacokinetics*; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
C052469:N-acetyl-S-(N-methylcarbamoyl)cysteine; D004126:Dimethylformamide; D000111:Acetylcysteine