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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
Author(s) -
Bertram J.,
Schettgen T.,
Kraus T.
Publication year - 2017
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.7972
Subject(s) - chemistry , chromatography , derivatization , gas chromatography–mass spectrometry , mass spectrometry , gas chromatography , urine , calibration curve , extraction (chemistry) , detection limit , sample preparation , solid phase extraction , biochemistry
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 on an 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 gas chromatography/tandem mass spectrometry (GC/MS/MS) 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 six calibration standards ranging from 50 μg/L to 2000 μg/L (10‐fold higher for H‐OPAA) in urine was prepared. Validation results were satisfactory 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 A quick and easy to use method has been established for six target molecules investigated for a better understanding of the metabolism of VP. Two of three substances identified as metabolites of VP could serve as a nonspecific human biomarker for VP exposure as shown with an excerpt of an exposure study performed in SD rats.