Quantification of six potential unspecific human biomarkers of 1-vinyl-2-pyrrolidone exposure in Sprague-Dawley rat urine using gas chromatography coupled with triple mass spectrometry.

RATIONALE The monomer 1-vinyl-2-pyrrolidone (VP) is a substance with excellent solvent features. It is used in a wide variety of pharmaceutical, cosmetic, food industrial or technical applications and produced in industrial scale. Since VP has caused adenocarcinoma of the nasal cavity and liver cell carcinoma in long term experiments with rats, a human biomarker would be appreciated for risk assessment. METHODS A sensitive analytical electron ionization GCMSMS method for the determination of six possible biomarkers for VP in urine was established and validated. Two isotope labeled internal standards (ISTD) were used for quantification. A simple and easy to use freeze drying step was performed prior to derivatization with N-tert-butyldimethylsilyl-N-methyltrifluoracetamide (MTBSTFA) and following sample extraction for cleanup purposes. RESULTS A calibration curve with 6 calibration standards ranging from 50 μg/L to 2000 μg/L (10 fold higher for H-OPAA) in urine was prepared. Validation results were satisfying with recoveries ranging from 88.2 to 110.2 % with two exceptions for the lowest quality control for two substances without ISTD (126.4 % and 139.3 %). Three of the substances could be identified as VP metabolites in an exposure study with Sprague-Dawley (SD) rats. CONCLUSIONS The paper provided describes a quick and easy to use method of six target molecules investigated for better understanding of the VP metabolization. Two of three substances identified as metabolites of VP might serve as a nonspecific human biomarker for a VP exposure as shown with an excerpt of an exposure study performed in SD rats.