Quantitative detection of bisphenol A and bisphenol A diglycidyl ether metabolites in human plasma by liquid chromatography–electrospray mass spectrometry

Hoshi University, Edo, Tōkyō, Japan
Journal of chromatography. B, Biomedical sciences and applications 01/2002; 765(2):121-126. DOI: 10.1016/S0378-4347(01)00393-0


Due to the ubiquity of epoxy resin compounds and their potential role in increasing the risk for reproductive dysfunction and cancer, the need for an assessment of human exposure is urgent. Therefore, we developed a method for measuring bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE) metabolites in human blood samples using high-performance liquid chromatography–electrospray ionization mass spectrometry (LC–MS). Human blood samples were processed using enzymatic deconjugation of the glucuronides followed by a novel sample preparation procedure using a solid-phase-cartridge column. This selective analytical method permits rapid detection of the metabolites, free BPA and a hydrolysis product of BADGE (BADGE-4OH) with detection limits in the low nanogram per milliliter range (0.1 ng ml−1 of BPA and 0.5 ng ml−1 of BADGE-4OH). The sample extraction was achieved by Oasis HLB column on gradient elution. The recoveries of BPA and BADGE-4OH added to human plasma samples were above 70.0% with a standard deviation of less than 5.0%. This selective, sensitive and accurate method will assist in elucidating potential associations between human exposure to epoxy-based compounds and adverse health effects.

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    • "However, LC–MS and LC–MS/MS techniques combine superiority over sensitivity, selectivity and precision even in low level concentration samples [8]. Thus far, a vast number of LC–MS and LC–MS/MS bioanalysis methods incorporated automated and/or on-line Solid Phase Extraction (SPE) sample preparation protocols [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] in order to minimize the contamination of the biosample from environmental background, and perceptibly decrease the lab bench work. However up to the present 1570-0232/© 2015 Elsevier B.V. All rights reserved. "
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    ABSTRACT: A rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and optimized for the simultaneous determination of bisphenol A, 4-t-octylphenol and 4-nonylphenol in human blood serum. For the first time, the electrospray ionization (ESI) parameters of probe position, voltage potential, sheath gas flow rate, auxiliary gas flow rate, and ion transfer tube temperature were thoroughly studied and optimized for each phenol by a univariate approach. As a consequence, low instrumental limits of detection were reported, demonstrating at 0.2ng/mL (in solvent matrix) excellent injection repeatability (RSD<14.5%) and a confirmation peak for all target phenols. Extraction and purification of serum was performed by the novel Hybrid Solid Phase Extraction-Precipitation Technology technique (Hybrid SPE-PPT). The limits of detection in human blood serum were 0.80, 1.3 and 1.4ng/mL for BPA, 4-t-OP and 4-NP, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
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    • "2000 HPLC with electrochemical detection 0.01 in solvent Healthy human serum 0.32 1.4 Coulometric array 0.05 in serum Inoue et al [113] 2001 LC-MS 0.1 Human plasma or serum ND -1.0 ND -4.4 BADGE Ikezuki et al [19] 2002 ELISA 0.3 in serum Female nonpregnant serum 2.0 ± 0.146 8.8 ± 0.64 Early pregnancy serum 1.5 ± 0.197 6.6 ± 0.86 Late pregnancy serum 1.4 ± 0.148 6.1 ± 0.65 Fetal (cord) serum 2.2 ± 0.318 9.6 ± 1.4 Amniotic fluid (15-18 wk) 8.3 ± 1.573 36.4 ± 6.9 Late amniotic fluid 1.1 ± 0.162 4.8 ± 0.71 Follicular fluid 2.4 ± 0.133 10.5 ± 0.58 Schonfelder et al [20] 2002 Derivatization-GC/MS 0.01 in serum Fetal (cord) serum 2.9 ± 0.411 12.7 ± 1.8 Maternal serum 4.4 ± 0.641 19.3 ± 2.8 Placenta 11.2 ± 1.512 ng/g tissue Takeuchi & Tsutsumi [23] 2002 ELISA 0.3 in serum Normal male serum 1.49 ± 0.11 6.5 ± 0.48 Total & free T, E, andostenedione, DHEAS, LH, FSH, prolactin PCOS female serum 1.04 ± 0.1 4.6 ± 0.44 Normal female serum 0.64 ± 0.1 2.8 ± 0.44 Tokada & Mori [114] 2002 GC-MS ? Umbilical cords at birth Mean, 4.4 ± 1.5; range, 0.11 -15.2 ng/g tissue Yamada et al [21] 2002 ELISA 0.5 Normal maternal serum 2.24 (median) 10.5 Normal fetal amniotic fluid 0.26 (median) 1.14 Abnormal fetal karyotype maternal serum 2.97 (median) 13.0 Abnormal fetal karyotype fetal amniotic fluid 0 (median) 0 Kuroda et al [115] 2003 HPLC Fluorescence derivation, column switching 0.04 Maternal serum 0.46 ± 0.067 2.0 ± 0.29 Fetal cord serum 0.62 ± 0.043 2.7 ± 0.19 Sterility female serum 0.46 ± 0.044 2.0 ± 0.19 Ascitic (peritoneal) fluid 0.56 ± 0.041 2.5 ± 0.18 "
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    ABSTRACT: The plastic monomer and plasticizer bisphenol A (BPA) is one of the highest volume chemicals produced worldwide. BPA is used in the production of polycarbonate plastics and epoxy resins used in many consumer products. Here, we have outlined studies that address the levels of BPA in human tissues and fluids. We have reviewed the few epidemiological studies available that explore biological markers of BPA exposure and human health outcomes. We have examined several studies of levels of BPA released from consumer products as well as the levels measured in wastewater, drinking water, air and dust. Lastly, we have reviewed acute metabolic studies and the information available about BPA metabolism in animal models. The reported levels of BPA in human fluids are higher than the BPA concentrations reported to stimulate molecular endpoints in vitro and appear to be within an order of magnitude of the levels needed to induce effects in animal models.
    Full-text · Article · Aug 2007 · Reproductive Toxicology
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    ABSTRACT: A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry with electrospray ionization in the positive mode (UPLC-(ESI) MS/MS) method was developed for the simultaneous determination of 16 bisphenol A diglycidyl ether (BADGE), novolac glycidyl ether (NOGE) and related compounds in canned foods. Three non-commercially available standards bisphenol F (2, 3-dihydroxypropyl) glycidyl ether (BFDGE·H2O), bisphenol F (3-chloro-2-hydroxypropyl) glycidyl ether (BFDGE·HCl) and bisphenol F (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether (BFDGE·H2O·HCl) were synthesized and used for qualitative analysis. Quantification of 13 analytes was carried out in multiple reaction monitoring mode using an external calibration, and the interference of matrixes was reduced by the matrix-matched calibration. The parameters of liquid chromatography and mass spectrometry were optimized to obtain maximum selectivity and sensitivity. The validation data obtained from oil-based and aqueous-based canned food matrixes showed low limit of detection, which ranged from 0.24 to 1.84 ng g−1, acceptable recovery (62.36–101.77 %) and good repeatability (RSD <10), all indicated this optimized method was suitable for the migration evaluation of BADGE, NOGE and their derivatives from can lacquer into food. Finally, this method was applied to the analysis of these compounds at low levels in diverse commercial canned samples.
    No preview · Article · Aug 2012 · European Food Research and Technology
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