Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N-methylsuccinimide in human plasma and urine using liquid chromatography-electrospray tandem mass spectrometry

A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These c ompounds are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used organic solvent. 5-HNMP and 2-HMSI were purified from plasma an d urine by solid-phase extraction using Isolute ENV+ columns, and analysed by liquid chromatography coupled to a mass spectrometer fitted with an atmo spheric pressure turbo ion spray ionisation interface in the positive ion m ode. The method was validated for plasma and urine concentrations from 0.12 to 25 mug/ml. The recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 9 8%, respectively, and in urine 111 and 106%, respectively. For 5-HNMP and 2 -HMSI, the within-day precision in plasma was 1-4 and 3-6%, respectively, a nd in urine 2-12 and 3-10%, respectively. The corresponding data for the be tween-day precision was 5 and 3-6%, respectively, and 4-6 and 7-8%, respect ively. The detection limit for 5-HNMP was 4 ng/ml in plasma and 120 ng/ml i n urine. For 2-HMSI, it was 5 ng/ml in plasma and 85 ng/ml in urine. The me thod is applicable for analysis of plasma and urine samples from workers ex posed to NMP. (C) 2001 Published by Elsevier Science B.V.