title: Rapid, automated online SPE-LC-QTRAP-MS/MS method for the simultaneous analysis of 14 phthalate metabolites and 5 bisphenol analogues in human urine.
abstract: Phthalates and bisphenol A (BPA) have received special attention in recent years due to their frequent use in consumer products and potential for adverse effects on human health. BPA is being replaced with a number of alternatives, including bisphenol S, bisphenol B, bisphenol F and bisphenol AF. These bisphenol analogues have similar potential for adverse health effects, but studies on human exposure are limited. Accurate measurement of multiple contaminants is important for estimating exposure. This paper describes a sensitive and automated method for the simultaneous determination of 14 phthalate metabolites, BPA and four bisphenol analogues in urine using online solid phase extraction coupled with high-performance liquid chromatography/tandem mass spectrometry using a hybrid triple-quadrupole linear ion trap mass spectrometer (LC-QTRAP-MS/MS), requiring very little sample volume (50µL). Quantification was performed under selected reaction monitoring (SRM) mode with negative electrospray ionization. The use of SRM combined with an enhanced product ion scan within the same analysis was examined. Unequivocal identification was provided by the acquisition of three SRM transitions per compound and isotope dilution. The analytical performance of the method was evaluated in synthetic and human urine. Linearity of response over three orders of magnitude was demonstrated for all of the compounds (R(2)>0.99), with method detection limits of 0.01-0.5ng/mL and limits of reporting of 0.07-3.1ng/mL. Accuracy ranged from 93% to 113% and inter- and intra-day precision were <22%. Finally, the validated method has been successfully applied to a cohort of pregnant women to measure biomarker concentrations of phthalates and bisphenols, with median concentrations ranging from 0.3ng/mL (bisphenol S) to 18.5ng/mL (monoethyl phthalate).
authors.affiliation: National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Rd, Coopers Plains, Brisbane, QLD 4108, Australia. Electronic address: amy.heffernan@uqconnect.edu.au.
authors.forename: A L
authors.initials: AL
authors.lastname: Heffernan
authors.affiliation: National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Rd, Coopers Plains, Brisbane, QLD 4108, Australia. Electronic address: k.leechue@uq.edu.au.
authors.forename: K
authors.initials: K
authors.lastname: Thompson
authors.affiliation: National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Rd, Coopers Plains, Brisbane, QLD 4108, Australia. Electronic address: g.eaglesham1@uq.edu.au.
authors.forename: G
authors.initials: G
authors.lastname: Eaglesham
authors.affiliation: National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Rd, Coopers Plains, Brisbane, QLD 4108, Australia. Electronic address: s.vijayasarathy@uq.edu.au.
authors.forename: S
authors.initials: S
authors.lastname: Vijayasarathy
authors.affiliation: National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Rd, Coopers Plains, Brisbane, QLD 4108, Australia. Electronic address: j.mueller@uq.edu.au.
authors.forename: J F
authors.initials: JF
authors.lastname: Mueller
authors.affiliation: Queensland Children's Medical Research Institute, and Children's Health and Environment Program, The University of Queensland, Centre for Children's Health Research, Level 7, 62 Graham St South, Brisbane, QLD, 4101, Australia. Electronic address: p.sly@uq.edu.au.
authors.forename: P D
authors.initials: PD
authors.lastname: Sly
authors.affiliation: National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Rd, Coopers Plains, Brisbane, QLD 4108, Australia. Electronic address: m.gomezramos@uq.edu.au.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gomez
mesh_terms: D001559:Benzhydryl Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007477:Ions / Q000737:chemistry; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000652:urine*; D010795:Phthalic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000652:urine*; D011247:Pregnancy; D012016:Reference Values; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000098923:Bisphenol B Compounds; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D007477:Ions; D010636:Phenols; D010795:Phthalic Acids; C581825:monoethyl phthalate; C492482:bisphenol B; D000098923:Bisphenol B Compounds; C032279:phthalic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Biomonitoring; Bisphenol A; Bisphenol analogues; LC–MS/MS; On-line solid phase extraction; Phthalates