Exposure marker discovery of di-2(propylheptyl) phthalate using ultra-performance liquid chromatography-mass spectrometry and a rat model

Chia-Lung Shih; Jen-Yi Hsu; Chien-Ping Tien; Yi-Ning Chung; Victor G Zgoda; Pao-Chi Liao

doi:10.1016/j.jfda.2018.11.002

Exposure marker discovery of di-2(propylheptyl) phthalate using ultra-performance liquid chromatography-mass spectrometry and a rat model

J Food Drug Anal. 2019 Apr;27(2):585-594. doi: 10.1016/j.jfda.2018.11.002. Epub 2018 Dec 11.

Authors

Chia-Lung Shih¹, Jen-Yi Hsu¹, Chien-Ping Tien¹, Yi-Ning Chung¹, Victor G Zgoda², Pao-Chi Liao¹

Affiliations

¹ Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
² Institute of Biomedical Chemistry, 119121 Moscow, Russia.

Abstract

Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer and has been suggested to be a subchronic toxicant in rats. DPHP has been approved to be used in food containers and handling by the U.S. Food and Drug Administration. The use of DPHP is still increasing, and the risk of human exposure to DPHP via food may be high. Exposure markers measured in human samples are commonly used to monitor human exposure levels. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a rat model were used to discover tentative DPHP exposure markers. DPHP and mono-(2-propylheptyl) phthalate (MPHP) were used as the precursors for calculating metabolite candidates using biotransformation mass changes of known enzymatic reactions. A rat model was designed to validate these metabolite candidates as tentative exposure markers. A total of 28 signals show dose-response relationships and these signals contain a few isomers. The chemical structures of 15 tentative exposure marker signals were speculated based on the product ion mass spectra from MS/MS analysis. These 15 signals included 7 chemical structures and some of them may be isomers. The different arrangement of the atoms in space of these isomers should be validated by standard compounds in the future studies. Among the 7 speculated chemical structures, 2 structures were novel tentative DPHP metabolites, and 5 structures have been previously reported in the literature. The results indicate that using UPLC-MS and a rat model can be used to identify tentative toxicant exposure markers.

Keywords: Biotransformation mass changes; Di-(2-propylheptyl) phthalate; Ultra-performance liquid chromatography-mass spectrometry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Biomarkers / metabolism
Biomarkers / urine
Chromatography, High Pressure Liquid
Disease Models, Animal*
Male
Phthalic Acids / administration & dosage
Phthalic Acids / metabolism
Phthalic Acids / urine*
Rats
Rats, Sprague-Dawley
Tandem Mass Spectrometry

Substances

Biomarkers
Phthalic Acids
bis(2-propylheptyl)phthalate

Grants and funding

This work was supported by grants (MOST105-2923-M-006-005-MY3 and MOST103-2113-M-006-003-MY3) from the Ministry of Science and Technology and by a grant (No 16-44-03007) from the Russian Scientific Foundation.