Development and validation of an analytical method for metabolites of the plasticizer tri-(2-ethylhexyl) trimellitate (TOTM) in human urine by LC-MS/MS

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2025-03-20 DOI:10.1016/j.jchromb.2025.124569

Paulien Cleys , Lucas Panneel , Philippe G. Jorens , Antonius Mulder , Adrian Covaci

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引用次数: 0

Abstract

Tri-(2-ethylhexyl) trimellitate (TEHTM or TOTM) is an alternative plasticizer used as replacement for conventional phthalates, such as bis-(2-ethyl-hexyl) phthalate (DEHP) in plastic materials. Migration studies show a lower leaching potential from the polymer matrix, compared to DEHP. Additionally, toxicological studies showed lower negative health effects of TOTM. A sensitive bioanalytical method is necessary to further enable the exposure assessment of TOTM. In this study, we developed a quantitative method based on SPE and LC-MS/MS for analysis of ten urinary metabolites of TOTM, such as 1,4-di-(2-ethylhexyl) trimellitate (1,4-DEHTM), 2,4-di-(2-ethylhexyl) trimellitate (2,4-DEHTM), 1-mono-(2-ethylhexyl) trimellitate (1-MEHTM), 2-mono-(2-ethylhexyl) trimellitate (2-MEHTM), 1-mono-(2-ethyl-5-carboxypentyl) trimellitate (5Cx-1-MEPTM), 2-mono-(2-ethyl-5-carboxypentyl) trimellitate (5Cx-2-MEPTM), 2-mono-(2-ethyl-5-hydroxyhexyl) trimellitate (5OH-2-MEHTM), and 1-mono-(2-ethyl-5-hydroxyhexyl) trimellitate (5OH-1-MEHTM), and 1-mono-(2-carboxymethylhexyl) trimellitate (2Cx-MMHTM). The method was validated according to the current ‘Bioanalytical Method Validation guidelines’ from European Medicines Agency (EMA). All validation criteria were successfully passed, except for 2Cx-MMHTM and 5Cx-2-MEPTM, which were discarded due to unsatisfactory validation results and low clinical relevance. Additionally, 1,4- and 2,4-DEHTM were successfully validated as a sum of two isomers. The validated method was applied to a pilot set of 30 urine samples from newborn patients. Significant higher urinary concentrations were found for 5Cx-1-MEPTM, 5OH-1-MEHTM, 5OH-2-MEHTM, 5oxo-1-MEHTM and 2-MEHTM in prematurely born babies from the neonatal intensive care unit (NICU) compared to term-born newborns. The current study expanded the range of analytes to eight TOTM metabolites which can be simultaneously analysed in urine samples. It also showed its clinical importance by analysing urine samples from newborns admitted to the NICU.

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.