BACKGROUND: The harmful effects of endocrine disrupting compounds (EDCs) on human health are generally well-known, and exposure during fetal development may have lasting effects. Fetal exposure to bisphenol A (BPA) has been recently relatively well-studied; however, less is known about alternatives such as bisphenol S (BPS), bisphenol F (BPF) and bisphenol AF (BPAF), which have started to appear in consumer products. Parabens are another widespread group of EDCs, with confirmed transplacental passage. The usage of many cosmetic, pharmaceutical and consumer products during the pregnancy that may contain parabens and bisphenols has led to the need for investigation. OBJECTIVES: To shed more light into the transplacental transport of BPA, its alternatives, and parabens, and to study their relation to fetal steroidogenesis. METHODS: BPA, BPS, BPF, BPAF, methylparaben, ethylparaben, propylparaben, butylparaben, benzylparaben and 15 steroids including estrogens, corticoids, androgens and immunomodulatory ones were determined in 27 maternal (37th week of pregnancy) and cord plasma samples using liquid chromatography - tandem mass spectrometry methods. RESULTS: In cord blood, significantly higher BPA levels (p=0.0455) were observed compared to maternal plasma. The results from multiple regression models showed that in cord blood, methylparaben (β=-0.027, p=0.027), propylparaben (β=-0.025, p=0.03) and the sum of all measured parabens (β=-0.037, p=0.015) were inversely associated with testosterone levels. CONCLUSION: To the best of our knowledge, this is the first study reporting the simultaneous detection of BPA, alternative bisphenols, parabens and steroids in maternal and cord plasma. Our study confirmed the transplacental transport of BPA, with likely accumulation in the fetal compartment. The negative association of cord blood parabens and testosterone levels points to possible risks with respect to importance of testosterone for prenatal male development.
- Klíčová slova
- Bisphenol, Endocrine disruptor, Paraben, Pregnancy, Steroid,
- MeSH
- benzhydrylové sloučeniny farmakokinetika farmakologie MeSH
- chromatografie kapalinová MeSH
- dospělí MeSH
- endokrinní disruptory * farmakokinetika MeSH
- estrogeny fyziologie MeSH
- fenoly farmakokinetika MeSH
- fetální krev * chemie MeSH
- lidé MeSH
- matka - expozice noxám MeSH
- novorozenec MeSH
- parabeny * farmakokinetika MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- bisphenol A MeSH Prohlížeč
- endokrinní disruptory * MeSH
- estrogeny MeSH
- fenoly MeSH
- parabeny * MeSH
A rapid and reliable method was developed to quantitate tolterodine and its 5-hydroxymethyl metabolite in human plasma using liquid chromatography-electrospray tandem mass spectrometry. The assay was based on liquid-liquid extraction of the compounds from plasma with tert-butylmethylether and hydrophilic interaction chromatography performed on a silica column (30mmx4.6mm, 3microm particles), the mobile phase consisted of acetonitrile-20mM ammonium acetate (70:30, v/v). Quantification was through positive-ion mode and selected reaction monitoring at m/z 326-->147 for tolterodine, 342-->223 for the 5-hydroxymethyl metabolite and 260-->183 for the internal standard propranolol, respectively. The lower limit of quantitation was 49 and 46pg/ml using 0.5ml of plasma for the parent drug and its metabolite, respectively and linearity was observed up to 30ng/ml. Within-day and between-day precision expressed by relative standard deviation was less than 11% and inaccuracy did not exceed 7% at all levels. The assay was applied to the analysis of samples from a pharmacokinetic study.
- MeSH
- benzhydrylové sloučeniny krev chemie farmakokinetika MeSH
- dospělí MeSH
- fenylpropanolamin krev chemie farmakokinetika MeSH
- kresoly krev chemie farmakokinetika MeSH
- lidé MeSH
- mladý dospělý MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- tolterodin tartarát MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- fenylpropanolamin MeSH
- kresoly MeSH
- tolterodin tartarát MeSH
Recent research provided evidence that effective H1-antihistaminic drugs need not exert a central and sedative action. Non-sedative H1-antihistaminics can aptly replace older combined preparations of classical H1-antihistaminics, motivated by an effort to weaken their sedative action by the concurrent administration of pharmaceutical preparations with a central stimulating action (e.g. Bromadryl F). The new group of non-sedative histamine H1-antagonists uses in a rational way changes of the physical and chemical properties of these substances or differences in their affinity to histamine H1-receptors in different areas to reduce the incidence of typical undesirable effects.
- MeSH
- antagonisté histaminu H1 * škodlivé účinky farmakokinetika MeSH
- astemizol MeSH
- benzhydrylové sloučeniny farmakokinetika MeSH
- benzimidazoly farmakokinetika MeSH
- lidé MeSH
- terfenadin MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- antagonisté histaminu H1 * MeSH
- astemizol MeSH
- benzhydrylové sloučeniny MeSH
- benzimidazoly MeSH
- terfenadin MeSH