PMID- 29687250 OWN - NLM STAT- MEDLINE DCOM- 20180814 LR - 20191210 IS - 1618-2650 (Electronic) IS - 1618-2642 (Linking) VI - 410 IP - 18 DP - 2018 Jul TI - Comprehensive monitoring of specific metabolites of tri-(2-ethylhexyl) trimellitate (TEHTM) in urine by column-switching liquid chromatography-tandem mass spectrometry. PG - 4343-4357 LID - 10.1007/s00216-018-1086-7 [doi] AB - Tri-(2-ethylhexyl) trimellitate (TOTM or TEHTM) is a substitute for the plasticizer di-(2-ethylhexyl) phthalate (DEHP). Here, a fast and robust HPLC method is presented for the first time enabling the simultaneous quantification of several TEHTM metabolites in urine. These are the three TEHTM monoester isomers 1-mono-(2-ethylhexyl) trimellitate (1-MEHTM), 2-mono-(2-ethylhexyl) trimellitate (2-MEHTM), and 4-mono-(2-ethylhexyl) trimellitate (4-MEHTM) as well as several selected side chain oxidized monoesters of TEHTM, namely, 1-mono-(2-ethyl-5-hydroxyhexyl) trimellitate (5OH-1-MEHTM), 2-mono-(2-ethyl-5-hydroxyhexyl) trimellitate (5OH-2-MEHTM), 1-mono-(2-ethyl-5-oxohexyl) trimellitate (5oxo-1-MEHTM), 2-mono-(2-ethyl-5-oxohexyl) trimellitate (5oxo-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-carboxymethylhexyl) trimellitate (2cx-2-MMHTM), and 1-mono-(2-carboxymethylhexyl) trimellitate (2cx-1-MMHTM). The method is characterized by a short sample preparation, for which the urine samples are enzymatically hydrolyzed and cleaned up by an online column arrangement. Separation of the analytes is enabled using liquid chromatography coupled with tandem mass spectrometry. Thus, in less than 30 min, 11 postulated metabolites of TEHTM can be selectively and sensitively quantified. The method is distinguished by its wide linear working range of up to 1800 mug/L with detection limits ranging from 0.3 mug/L (for 5oxo-1-MEHTM) to 1.5 mug/L (for 1-MEHTM). Precision and repeatability of the method were proven with determined relative standard deviations between 2.5 and 11.3%. The selection of the analytes of this method was based on a pilot study, by which several potential TEHTM metabolites were investigated in human urine of an orally exposed volunteer. Thus, the here presented method is a perfect tool for human biomonitoring of TEHTM exposure. Graphical abstract Analysis of several postulated TEHTM metabolites in human urine using LC-MS/MS. FAU - Hollerer, Christine AU - Hollerer C AD - Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Henkestr. 9-11, 91054, Erlangen, Germany. FAU - Goen, Thomas AU - Goen T AD - Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Henkestr. 9-11, 91054, Erlangen, Germany. FAU - Eckert, Elisabeth AU - Eckert E AD - Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Henkestr. 9-11, 91054, Erlangen, Germany. elisabeth.eckert@fau.de. LA - eng PT - Journal Article PT - Validation Study DEP - 20180424 PL - Germany TA - Anal Bioanal Chem JT - Analytical and bioanalytical chemistry JID - 101134327 RN - 0 (Benzoates) RN - 0 (Plasticizers) RN - 3319-31-1 (tri-(2-ethylhexyl)trimellitate) SB - IM MH - Benzoates/metabolism/*urine MH - Calibration MH - Chromatography, Liquid/*methods MH - Environmental Monitoring/*methods MH - Humans MH - Limit of Detection MH - Pilot Projects MH - Plasticizers/*metabolism MH - Reference Standards MH - Reproducibility of Results MH - Tandem Mass Spectrometry/*methods OTO - NOTNLM OT - Biomonitoring OT - Core-shell material OT - Human metabolism OT - Medical devices OT - Plasticizer OT - Tri-(2-ethylhexyl) trimellitate EDAT- 2018/04/25 06:00 MHDA- 2018/08/15 06:00 CRDT- 2018/04/25 06:00 PHST- 2018/02/01 00:00 [received] PHST- 2018/04/13 00:00 [accepted] PHST- 2018/03/21 00:00 [revised] PHST- 2018/04/25 06:00 [pubmed] PHST- 2018/08/15 06:00 [medline] PHST- 2018/04/25 06:00 [entrez] AID - 10.1007/s00216-018-1086-7 [pii] AID - 10.1007/s00216-018-1086-7 [doi] PST - ppublish SO - Anal Bioanal Chem. 2018 Jul;410(18):4343-4357. doi: 10.1007/s00216-018-1086-7. Epub 2018 Apr 24.