Development of a liquid chromatography/atmospheric pressure photo-ionization high-resolution mass spectrometry analytical method for the simultaneous determination of polybrominated diphenyl ethers and their metabolites: application to BDE-47 metabolism i (original) (raw)
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Rapid Communications in Mass Spectrometry, 2010
Hydroxylated polybrominated diphenyl ether (OH-PBDEs) metabolites have the potential to cause endocrine disruption as well as other health effects. Currently, gas chromatography/mass spectrometry (GC/MS) after derivatization is used for the analysis of OH-PBDEs. However, there is a need for the direct analysis of OH-PBDEs at relatively low concentrations in environmental and biological samples. Liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry (LC/APCI-MS/MS) was evaluated for the analysis of nine OH-PBDEs, ranging from tri-to hexabrominated. Separation of the nine isomeric metabolites was achieved with reversedphase liquid chromatography, followed by detection by APCI-MS in negative mode. Notably, a significant decrease in ionization was observed in 6-hydroxyl-substituted PBDE metabolites in the presence of an ortho-substituted bromine, relative to the other hydroxylated metabolites. This is probably due to the formation of dioxins in the source as a result of the high-temperature conditions, which prevented ionization by hydrogen abstraction. The MS/MS experiments also provided evidence of the neutral losses of HBr and Br 2 , indicating the possible use of neutral loss scanning and selected reaction monitoring (SRM) for the screening of brominated metabolites in samples. The applicability of LC/APCI-MS/MS was demonstrated for the analysis of metabolites of BDEs 47 and 99 formed in human liver microsomes. The LC/APCI-MS/MS method was able to detect metabolites that had previously been identified by GC/MS following derivatization. Analysis of OH-PBDEs by LC/APCI-MS/MS 2229 Product ions (m/z) 6-hydroxy-2,3,3',4,4',5'-hexabromodiphenyl ether 33.77 654, 656, 658, 660 573, 575, 577, 579, 581, 495, 497, 499, 501, 503 6-OH-BDE157
Rapid Communications in Mass Spectrometry, 2005
A method based on gas chromatography (GC) separation followed by ion trap tandem mass spectrometry detection in EI mode (ITD-MS/MS), using isotope dilution, was developed for the determination of ten native polybrominated diphenyl ethers (PBDEs) and four 13 C 12-labeled congeners in biological (fat tissue and human serum) and food samples. The highest-mass fragment ions were used as precursor ions for those congeners with molecular ions with m/z values higher than the maximum of the instrument. In these cases (hepta-BDEs and 13 C 12-hexa-BDEs) no fragmentation was achieved under the experimental conditions employed. Repeatability (lower than 9%) and reproducibility (lower than 13%), expressed as relative standard deviation (RSD, n ¼ 3 and 4, respectively), were satisfactory. Similarly, the coefficient of variation (n ¼ 4) of the isotopic ratio between the two most abundant product ions was lower than 10 and 6% for native and labeled congeners, respectively. To evaluate the feasibility of the method, the optimized isotope dilution GC/ ITD-MS/MS method was used for the quantitation of selected PBDE congeners in different samples including adipose tissue, human serum and foodstuff samples, from three inter-laboratory comparative exercises, covering a wide range of concentrations. A solid-phase extraction procedure, previously developed for PCB determination in small-size bird serum samples, was successfully applied to quantification of PBDEs in 1 mL samples of human serum.
Chemosphere, 2012
Hydroxylated polybrominated diphenyl ethers (OH-PDBEs) are exogenous, bioactive compounds that originate, to a large extent, from anthropogenic activities, although they are also naturally produced in the environment. In the present study nine new authentic OH-PBDE reference standards and their corresponding methyl ether derivatives (MeO-PBDEs) were synthesised and characterised by NMR spectroscopy and mass spectrometry. Seven of the authentic reference standards prepared were thereafter tentatively identified in a pooled human blood sample. The tentatively identified OH-PBDEs were 3-hydroxy-2,2 0 ,4,4 0 ,6-pentabromodiphenyl ether, 3 0 -hydroxy-2,2 0 ,4,4 0 ,6-pentabromodiphenyl ether, 3-hydroxy-2,2 0 ,4,4 0 ,5-pentabromodiphenyl ether, 3-hydroxy-2,2 0 ,4,4 0 ,5,6 0 -hexabromodiphenyl ether, 3 0 -hydroxy-2,2 0 ,4,4 0 ,5,6 0 -hexabromodiphenyl ether, 3-hydroxy-2,2 0 ,4,4 0 ,5,5 0 -hexabromodiphenyl ether and 4-hydroxy-2,2 0 ,3,4 0 ,5,5 0 ,6-heptabromodiphenyl ether. An additional seven OH-PBDEs were tentatively identified in the pooled human blood sample, of which one OH-PBDE, 4 0 -hydroxy-2,2 0 ,4,5,5 0 -pentabromodiphenyl ether, has not been identified in human blood before. The identification was performed using gas chromatography-mass spectrometry (GC-MS) recording the bromine ions m/z 79, 81. The tentative identification was supported by the peaks relative retention times (RRTs) compared to authentic references on two GC columns of different polarities for the hexa-, and heptabrominated OH-PBDEs, and three different GC columns for the pentabrominated OH-PBDEs. The OH-PBDE congeners most likely originate from human metabolism of a flame retardant, i.e. polybrominated diphenyl ethers (PBDEs), due to the relatively high concentrations of PBDEs in the same human blood sample and the fact that these PBDEs could form the tentatively identified OH-PBDEs via metabolic direct hydroxylation or via 1,2-shift.
Journal of Chromatography B-analytical Technologies in The Biomedical and Life Sciences, 2005
A simple, rapid, sensitive and reproducible method based on solid-phase extraction (SPE) and acidified silica clean-up was developed for the measurement of 12 polybrominated diphenyl ethers (PBDEs), including BDE 209, in human serum. Several solid-phase sorbents (Empore TM C 18 , Isolute Phenyl, Isolute ENV+ and OASIS TM HLB) were tested and it was found that OASIS TM HLB (500 mg) gives the highest absolute recoveries (between 64% and 95%, R.S.D. < 17%, n = 3) for all tested analytes and internal standards. Removal of co-extracted biogenic materials was performed using a 6 ml disposable cartridge containing (from bottom to top) silica impregnated with sulphuric acid, activated silica and anhydrous sodium sulphate. PBDEs and BB 153 were quantified using a gas chromatograph coupled with a mass spectrometer (MS) operated in electron-capture negative ionization mode. The method limits of quantification (LOQ) ranged between 0.2 and 25 pg/ml serum (0.1 and 4 ng/g lipid weight). LOQs were dependent on the analyte levels in procedural blanks which resulted in the highest LOQs for PBDE congeners found in higher concentrations in blanks (e.g. BDE 47, 99 and 209). The use of OASIS TM HLB SPE cartridge allowed a good method repeatability (within-and between-day precision < 12% for all congeners, except for BDE 209 < 17%, n = 3). The method was applied to serum samples from a random Belgian population. The obtained results were within the range of PBDE levels in other non-exposed population from Europe.
Environmental Health Perspectives, 2007
Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental contaminants that are found in both abiotic and biotic environmental samples (Hites 2004; Streets et al. 2006). PBDEs are used as flame retardants; the three main commercial types of PBDE are penta-BDE, octa-BDE, and deca-BDE. DE-71, a widely used commercial penta-BDE product, is generally composed of 50-60% penta-BDE congeners, 24-38% tetra-BDE congeners, and 4-8% hexa-BDE congeners (Birnbaum and Staskal 2003). Since the 1970s, penta-BDE has been used as a flame retardant in polyurethane foam-containing consumer goods such as carpet padding, sofas, and mattresses; this flame retardant can account for up to 30% by weight of the foam (Hale et al. 2002). DE-71 also has minor uses in phenolic resins, polyesters, and epoxy. Despite its relatively small global production and usage compared with deca-BDE, the congeners in penta-BDE, such as 2,2´,4,4´-tetrabromodiphenyl ether (BDE-47), 2,2´,4,4´,5pentabromodiphenyl ether (BDE-99), and 2,2´,4,4´,5,5´-hexabromodiphenyl ether (BDE-153), are the most common PBDE congeners found in environmental samples, Materials and Methods Chemicals. We obtained commercial DE-71 from the Great Lakes Chemical Corporation (West Lafayette, IN). Dimethyl sulfoxide and β-estradiol-3-benzoate were purchased from Sigma Chemical Co. (St. Louis, MO), and corn oil was purchased from ICN Biomedicals (Aurora, OH). We purchased all of the neutral standards (
Analytical Chemistry, 2009
A total of 14 tetra-to deca-PBDE congeners were separated on a C 18 reversed phase liquid chromatographic column. PBDEs 47, 85, 99, 100, 153, 154, 183, 196, 197, 203, 206, 207, 208, and 209 were eluted using a gradient methanol/water/toluene mobile phase system at a flow rate of 0.5 mL min -1 . 13 C-BDE-47, 13 C-BDE-99, 13 C-BDE-153, BDE-128, and 13 C-BDE-209 were used as internal standards, while 13 C-BDE-100 was used as a syringe standard. Separated analytes were ionized using an atmospheric pressure photoionization (APPI) source equipped with a 10 eV krypton lamp and operated in negative ion mode. [M-Br + O]ions were monitored as precursor ions for all studied PBDEs, except for BDE-208 and BDE-209 which produced higher intensity at the [C 6 Br 5 O]ion cluster.
Talanta, 2013
Sensitive and reliable methods for simultaneous determination of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in limited volumes of human serum or plasma need to be further documented especially when they accumulate at low levels that are still capable of disrupting endocrine and immune functions, and affecting neurodevelopment and reproduction. The objective of this study was to develop and validate a sensitive and quantitative method that simultaneously quantifies PBDEs and PCBs in 0.5 ml of human serum or plasma. We optimized a solid-phase extraction (SPE) method and used silica particle purification for the extraction of PBDEs and PCBs. Two multiple reactions monitoring (MRM) transitions were optimized for each congeners. The sum of the transitions was used for quantification, and their abundance ratios were used for identification. The combined method optimization techniques resulted in limits of detection from 3-145 pg/ml for 10 PBDEs and 1-12 pg/ml for 15 PCBs. Method was solidly validated by analyzing serum fortified with a certified PBDE and PCB standard mixture from the National Institute of Standards and Technology (NIST). The accuracy was 88-118% and day-today precision was within 19%. The method was successfully applied to quantify native concentrations of PBDE and PCB in commercially available human serum. The sensitivity and selectivity of the GC/EI-MS/MS analysis enables it to be the method of choice for investigations of exposures to PBDE and PCB congeners, especially when sample volume is limited.
Journal of Chromatography A, 2011
Dispersive solid-phase extraction (DSPE) is proposed for the first time as a simplified, fast and low cost clean-up technique of biological sample extracts for polybrominated diphenyl ethers (PBDEs) determination. The combination of a traditional extraction technique, such as ultrasound-assisted leaching (USAL) with DSPE was successfully applied for sample preparation prior to gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. The analytes were first extracted from 1 g homogenized sample in n-hexane:dichloromethane (8:2) by applying USAL technique and further cleaned-up using DSPE with 0.20 g C 18 -silica as sorbent material. Different solvent mixtures, sorbent type and amount, and lipid digestion procedures were evaluated in terms of clean-up and extraction efficiency. Under optimum conditions, the method detection limits (MDLs) for PBDEs, calculated as three times the signal-to-noise ratio (S/N) were within the range 9-44 pg g −1 wet weight. The calibration graphs were linear within the concentration range of 53-500,000 pg g −1 , 66-500,000 pg g −1 , 89-500,000 pg g −1 and 151-500,000 pg g −1 for BDE-47, BDE-100, BDE-99 and BDE-153, respectively; and the coefficient of determination (r 2 ) exceeded 0.9992 for all analytes. The proposed methodology was compared with a reference solid-phase extraction technique. The applicability of the methodology for the screening of PBDEs has been demonstrated by analyzing spiked and real samples of biological nature (fish, egg and chicken) with different lipid content as well as reference material (WELL-WMF-01). Recovery values ranged between 75% and 114% and the measured concentrations in certified material showed a reasonable agreement with the certified ones. BDE-47, BDE-100 and BDE-99 were quantified in three of the seven analyzed samples and the concentrations ranged between 91 and 140 pg g −1 . In addition, this work is the first description of PBDEs detected in fish of Argentinean environment.
Analytica chimica acta, 2015
The presence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH-BDE) and methoxylated (MeO-BDE) analogs in humans is an area of high interest to scientists and the public due to their neurotoxic and endocrine disrupting effects. Consequently, there is a rise in the investigation of the occurrence of these three classes of compounds together in environmental matrices and in humans in order to understand their bioaccumulation patterns. Analysis of PBDEs, OH-BDEs, and MeO-BDEs using liquid chromatography-mass spectrometry (LC-MS) can be accomplished simultaneously, but detection limits for PBDEs and MeO-BDEs in LC-MS is insufficient for trace level quantification. Therefore, fractionation steps of the phenolic (OH-BDEs) and neutral (PBDEs and MeO-BDEs) compounds during sample preparation are typically performed so that different analytical techniques can be used to achieve the needed sensitivities. However, this approach involves multiple injections, ultimately increa...