MSACL 2018 US Abstract


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Topic: Small Molecules / Tox

High-Throughput UPLC-MS/MS Analysis of 28 Urinary Metabolites of Toxic and Carcinogenic Volatile Organic Compounds

Victor De Jesus (Presenter)
Centers for Disease Control and Prevention

Bio: I am the Volatile Organic Compounds Laboratory (VOCL) Chief at the Tobacco and Volatiles Branch, Centers for Disease Control and Prevention (CDC). VOCL supports CDC's public health mission by developing methods and measuring harmful VOCs (and their metabolites) in blood and urine of individuals exposed to tobacco products, tobacco smoke and other emissions. Current scientific interests include measuring biomarkers of harmful VOC exposures by mass spectrometric techniques.

Authorship: Víctor R. De Jesús, Deepak Bhandari, Benjamin C. Blount
Tobacco and Volatiles Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA

Short Abstract

Volatile organic compounds (VOCs) are ubiquitous in the environment. Long-term exposure to certain VOCs may increase the risk for cancer and birth defects. In the U.S. tobacco smoke is the major non-occupational source of exposure to harmful VOCs. Characterizing human exposure to carcinogenic VOCs is of significant public health interest. We developed a UPLC-ESI-MS/MS method to quantify urinary VOC metabolites to detect 28 metabolites from exposure to 20 VOCs. The method is rugged and allows high-throughput analysis of urine specimens. It improves studies related to human exposure and health effects by providing reliable estimates of population exposure to VOCs.

Long Abstract

Introduction

Volatile organic compounds (VOCs) are ubiquitous in the environment. Long-term exposure to certain VOCs may increase the risk of cancer and birth defects. In the U.S. tobacco smoke is the major non-occupational source of exposure to a number of harmful VOCs (e.g., acrolein, acrylamide, acrylonitrile, benzene, 1,3-butadiene, crotonaldehyde, dimethylformamide, ethylbenzene, propylene oxide, styrene, toluene, and xylenes). Characterizing human exposure to carcinogenic VOCs is of significant public health interest. We aimed to develop a method to quantify urinary metabolites of harmful VOCs as part of large population studies.

Methods

We developed an ultra-high performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method to quantify urinary VOC metabolites (Alwis et al., 2012) to characterize the urinary levels of VOC metabolites in a representative sample of the US population. NHANES is a population-based survey designed to assess the health and nutritional status of adults and children in the U.S. (https://www.cdc.gov/nchs/nhanes/index.htm). Spot urine specimens were collected from participants in NHANES survey cycles. The method detects 28 metabolites resulting from exposure to 20 VOCs, including 14 compounds classified as carcinogenic or likely carcinogenic by the International Agency for Research on Cancer. Urine samples were analyzed at 1:10 dilution. Liquid chromatography was performed using an ACQUITY UPLC HSS T3 Column, 1.8 µm, 2.1 mm x 150 mm, with mobile phases containing 15 mM ammonium acetate, pH 6.8 (solvent A) and acetonitrile (solvent B). The mass spectrometer was operated in negative ion scheduled multiple reaction monitoring (SMRM) mode.

Results

The high-throughput method is accurate, sensitive and precise. We examined urine specimens collected from non-smokers and smokers, resulting in robust reference ranges for the U.S. population. Exclusive tobacco smokers were distinguished from non-tobacco users through a combination of self-reporting and serum cotinine data.

Conclusions & Discussion

Urinary VOC metabolites are useful biomarkers of exposure to harmful VOCs. The method is rugged and allows high-throughput analysis of urine specimens. It improves studies related to VOC exposure and health effects such as cancer and birth defects by providing reliable estimates of population exposure to over 20 harmful and/or carcinogenic VOCs.


References & Acknowledgements:

References: Alwis, K. U., Blount, B. C., Britt, A. S., Patel, D., & Ashley, D. L. (2012). Simultaneous analysis of 28 urinary VOC metabolites using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). Anal Chim Acta, 750, 152-160.

Acknowledgements: The authors thank the National Center for Health Statistics and Westat for planning and directing the National Health and Nutrition Examination Survey (NHANES). At the National Center for Environmental Health, we thank the Urinary VOC Metabolites Team, Volatile Organic Compounds Laboratory for the analysis of >10,000 NHANES urine samples. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.


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