Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker

Objectives The aims were to study the toxicokinetics of 5-hydroxy-N-methyl- 2-pyrrolidone (5-HNMP) in blood and urine after exposure to N-methyl-2-pyrr olidone (NMP) and to study the suitability of 5-HNMP as a biomarker for ass essing NMP exposure. Methods Six male volunteers were exposed for 8 hours to NMP concentrations of 0, 10, 25, and 50 mg/m(3). Blood and urine were sampled before, during, and up to 40 hours after exposure. Aliquots of urine and plasma were purifi ed, derivatized, and analyzed for 5-HNMP on a gas chromatograph/mass spectr ometer in the electron impact mode. Results The mean plasma concentration [P-(5-HNMP)] after 8-hour NMP exposur e to 10, 25, and 50 mg/m(3) was 8.0, 19.6, and 44.4 mu mol/l, respectively. The mean urinary concentration [U-(5-HNMP)] for the 2 last hours of exposu re was 17.7, 57.3, and 117.3 mmol/mol creatinine, respectively. The maximal P-(5-HNMP)and U-(5-HNMP) concentrations occurred 1 hour and 0-2 hours, res pectively, after the exposure. The half-times of P-(5-HNMP) and U-(5-HNMP) were 6.3 and 7.3 hours, respectively. The 5-HNMP urinary concentrations wer e 58% of the calculated retained dose. There was a close correlation (r) be tween P-(5-HNMP) (r=0.98) and U-(5-HNMP) (r=0.97) with NMP exposure. Conclusions 5-HNMP is an excellent biomarker for assessing exposure to NMP. Its plasma and urinary half-times (6-7 hours), the minimal risk for contam ination during sampling in occupational settings, and the close correlation of P-(5-HNMP) and U-(5-HNMP) with NMP exposure makes 5-HNMP suitable for m onitoring exposure to NMP. 5-HNMP in plasma is recommended.