Determination of 18 phthalate metabolites in human urine using a liquid chromatography-tandem mass spectrometer equipped with a core–shell column for rapid separation

Abstract

Phthalates are a group of chemicals used in a variety of products worldwide. Exposure to some phthalates is considered to be potentially harmful to human health. Measuring specific metabolites of the phthalates in urine is becoming popular in estimating human exposure to phthalates. In this study, a sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed for the simultaneous determination of 18 phthalate metabolites in human urine. A high efficiency core–shell column allows for a fast separation that is comparable to ultra high performance liquid chromatography (UHPLC) methods. An off-line solid-phase extraction (SPE) was used to clean up the sample matrix. The method detection limit defined as three times the signal to noise ratio in spiked pooled urine samples was achieved in the range of 0.03–1.4 ng mL⁻¹ urine for the 18 target analytes. The developed method has been applied to measure the 18 phthalate metabolites in urine samples of 150 Canadian men. Eleven major metabolites associated with seven parent phthalates, namely diethylphthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), di-n-octylphthalate (DOP), di-n-butyl phthalate (DBP), diisobutyl phthalate (DiBP), butylbenzylphthalate (BBzP), and dimethylphthalate (DMP), were detected in these samples, among which the metabolites of DEP and DEHP dominated the distribution of all phthalate metabolites detected in the urine samples with mean values of 191.4 and 101.8 ng mL⁻¹ in urine, respectively. The concentrations of phthalate metabolites in this study were found to be similar to those findings in the Canadian Health Measures Survey 2007–2009 (CHMS) and other international studies. The results also demonstrated that the developed method is a robust and reliable method for monitoring of phthalate metabolites in urine samples.