Analysis of terephthalate metabolites in human urine by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Aug 15;1092:473-479. doi: 10.1016/j.jchromb.2018.06.044. Epub 2018 Jun 20.


Owing to their toxicity, phthalate plasticizers are currently being replaced with terephthalates in many consumer products. Nevertheless, data on human exposure to and toxicity of terephthalates are still scarce. In this study, we developed a robust analytical method for the measurement of six terephthalate metabolites (TPhMs) in human urine through their successful separation from phthalate metabolites (PhMs). Target analytes were identified, using commercially available standards, and quantified with isotopically labeled internal standards (IS). The limits of quantification (LOQ) of TPhMs were in the range of 0.12 to 0.4 ng/mL, with the exception of 2.8 ng/mL for terephthalic acid (TPA) and 3.75 ng/mL for mono-(2-ethylhexyl) terephthalate (mEHTP), which were found in procedural blanks at notable levels. The method developed in this study showed excellent accuracy (recoveries: 86-117%) and precision (RSD: 0.6-12.2%) for TPhMs. The method was successfully applied for the analysis of 30 human urine samples collected from individuals with no known history of occupational exposure. The detection frequencies (df %) of TPhMs in urine ranged between 26.6 and 100%. This is one of the first studies that report a method for the analysis of emerging class of environmental chemicals in human specimens.

Keywords: HPLC-MS/MS; Human biomonitoring; Method validation; Phthalate replacements; Plasticizers; Terephthalate metabolites.

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid / methods*
  • Environmental Exposure / analysis
  • Female
  • Humans
  • Limit of Detection
  • Linear Models
  • Male
  • Phthalic Acids / chemistry
  • Phthalic Acids / isolation & purification
  • Phthalic Acids / urine*
  • Plasticizers / analysis*
  • Plasticizers / chemistry
  • Plasticizers / isolation & purification
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*


  • Phthalic Acids
  • Plasticizers
  • terephthalic acid