A new hydrophobic deep eutectic solvent composed of menthol and tris(2-ethylhexyl) phosphate for solvent bar microextraction of parabens from biological fluids

Parabens are antimicrobial preservatives with extensive applications in cosmetics,toiletries,pharmaceuticals,and food.Considering the legitimate concerns relating to their potential to disrupt multiple endocrine functions,it becomes imperative to prioritize the development of innovative bioanalytical techniques for effectively monitoring their presence in biological samples.In this study,an efficient solvent bar microextraction(SBME)was established,utilizing new hydrophobic deep eutectic solvents(DEs)to determine methylparaben and propylparaben in urine and plasma samples.The DEs comprising menthol and tris(2-ethylhexyl)phosphate(M-TEHP)at various molar ratios were synthesized for the first time to enhance the extraction capacity and promote the eco-friendliness of the DE used as an extraction solvent.Fourier-transform infrared(FT-IR)and proton nuclear magnetic resonance(1H NMR)spectroscopies were employed to confirm and investigate the properties of the successful synthesis(M-TEHP)DE at a molar ratio of 1:1.The synthesized DE exhibits low microbial toxicity and can be considered an eco-friendly solvent for extraction.Furthermore,quantum-chemical calculations were utilized to predict synthesized DE's structure and interaction energy with selected parabens.The influential operational factors of DE-SBME on the extraction efficiency(EE%)of both parabens were evaluated using response surface methodology based on central composite design,and a total of 30 extraction tests were conducted to determine the optimal conditions.The optimized DE-SBME,in combination with HPLC-DAD,exhibited low detection limits(0.54–0.91μg L^(−1)),excellent linearity(R^(2)≥0.9993),precise results(RSDs≤7.6%),satisfactory recoveries(92–97%)and negligible matrix effects.Hence,it had remarkable effectiveness and applicability in determining selected parabens in real urine and plasma samples.

Bio-screening and quantification of methyl paraben in vinegar and coconut juice separated by HPTLC

As a widely used food preservative,methyl paraben was experimentally evidenced with serious hormonelike adverse effects.Herein,a high performance thin-layer chromatography platformed bioluminescent bioautography and image analysis for the selective quantification and confirmation of methyl paraben was proposed and validated in vinegar and coconut juice.First,the detectability of the bioautography to the analyte on different layer materials was estimated,revealing that normal silica gel was the best choice.After that,the liquid of sample extract and working solution were separated to overcome the background noises due to co-extracted matrices.The separation result was then coupled to the optimized bioautography,enabling instant and straightforward screening of the targeted conpound.For accurate quantification,bioluninescent inhibition pattern caused by the analyte was processed by image analysis,giving useful sensitivity(LOD>16 mg/kg),precision(RSD<10.1%)and accuracy(spike-recovery rate 76.9%-112.2%).Finally,the suspected result was confirmed by determining its MS fingerprint,further strengthening the reliability of screening.

Dispersive Liquid-liquid Microextraction for Simultaneous Determination of Six Parabens in Aqueous Cosmetics

A simple and rapid sample preparation method of dispersive liquid-liquid microextraction（DLLME） was applied in the simultaneous determination of six parabens in the aqueous cosmetics. The analysis was performed on gas chromatography coupled with a flame ionization detection（GC-FID）. The mixed solution containing 30 μL of chloroform（extraction solvent） and 300 μL of tetrahydrofuran（dispersive solvent） was rapidly injected into the sample solution for the purpose of microextraction. After that, the solution mentioned above was centrifuged at 4000 r/min for 10 min, and then the organic sediment phase was detected by GC-FID. The effects of experimental parameters, such as the extraction solvent and the volume of it, and the dispersive solvent and the volume of it, on the yield of the extraction were studied in detail. Under the optimum conditions, the enrichment factors of the target analytes range from 87 to 214. Linearity ranges are 0.05-10.0μg/mL for methylparaben and 0.025--5.0 μg/mL for the other five parabens. The relative standard deviations（RSDs） are lower than 8.2%（n=6）. The proposed method was applied to the analysis of six parabens in eleven aqueous cosmetics. The recoveries of the target analytes in the spiked real samples are in the range of 81.0%-103%.

A Rapid Separation and Highly Determination of Paraben Species by Ultra-Performance Liquid Chromatography —Electrochemical Detection

In this study, a new technique was developed using rapid ultra-performance liquid chromatography (UPLC)-based separation coupled with electrochemical detection by a boron-doped diamond (BDD) electrode for the detection and quantification of three commonly used parabens (methylparaben (MP), ethylparaben (EP) and propylparaben (PP)). We aimed to reduce the analysis time by using UPLC coupled with a short reverse phase C 18 monolithic column (25 mm×4.6 mm). Operating the monolithic column at low back-pressure resulted in high flow rates. A mobile phaseconsisting of a 25:75 (v/v) ratio of acetonitrile:0.05 Mphosphate buffer (pH 5) at a flow rate of 2.5 mL·min?1 was used to perform the separation. The amperometric detection with the BDD electrode was found to be optimal and reliably reproducible at a detection potential of 1.5 V vs. Ag/AgCl. Under these conditions, the separation of the three targetanalytes (MP, EP and PP) was achieved in 2 min and was linear within a sample concentration range of 0.1 to 50.0 mg·L?1 (r2 values of 0.9970, 0.9994 and 0.9994 for MP, EP and PP, respectively). This method was successfully applied to determine the concentrations of each parabeninsix real samples with therecoveries ranging from of 80.3% - 98.9% for all three parabensfrom samples spiked at 12, 22 and 32 mg·L?1. Therefore, the proposed method can be used as an alternative rapid and selective method for the determination of paraben levels in real samples.

Photofading of Derivatives of Paraben (PHB) by AM1 and PM3 Methods: A Theoretical Study

Calculations of chemical structures and photofading of parabens (PHB—4 hydroxybenzoic acid), which are p-hydroxybenzoic acid alkyl esters were performed. These compounds are used as preservatives for the substances used in cosmetics. The reactivity of these derivatives with an oxidant—singlet oxygen—have been tested with a theoretical method of frontier orbitals. All-valence molecular orbital methods, AM1 and PM3, have been used to calculate frontier electron density for higher occupied HOMO and lower unoccupied LUMO orbitals, which might be sensitive to an electrophilic (with singleton oxygen atom 1O2) or nucleophilic ( superoxide anion radical) attack at a particular atom in a molecule. Using AM1 and PM3, we calculated the reactivity , superdelocalisability and electron density distributions. The obtained superdelocalisability rates allow you to explain the fastness values in different chemical molecules. The structure of parabens (PHB) was optimized by MM+, DM, AM1 or PM3, to achieve constant energy values at a convergence criterion of 0.01 kcal/mol. The performed calculations indicate that the electrophilic oxidation reaction should take place in the aromatic ring in the 2-position to the hydroxyl residue of PHB, whereas the superoxide radical reaction occurs mainly on the alkyl residues of the ester group. The reaction may take place according to superoxide mechanism or 1,2-addition, where the higher superdelocalisability values SN are located on neighboring atoms in aromatic systems.

Quick Single Run Capillary Zone Electrophoresis Determination of Active Ingredients and Preservatives in Pharmaceutical Products

The paper deals with the development of a rapid and efficient Capillary Zone Electrophoresis (CZE) method for Quality Control analysis of pharmaceutical preparations containing antihistamines, decongestants, anticholinergic remedies and preservatives. Active ingredients of interest are: ChlorPheniramine Maleate (CPM), DiPhenhydramine Hydrochloride (DPH), Ephedrine hydrochloride (E), Isopropamide Iodide (II), Pheniramine Maleate (PM), Lidocaine hydrochloride (L), Tetracaine hydrochloride (T), Clopamide Hydrochloride (CH), DiHydroErgochristine (DHE), PhenylEphrine hydrochloride (PE) and Acetaminophen (A). Preservatives studied are: MethylParaben (MeP), EthylParaben (EtP), PropylParaben (PrP), ButylParaben (BuP), p-HydroxyBenzoic Acid (p-HBA). All these analytes were separated in a single run using 60 mM tetraborate buffer solution (TBS) pH = 9.2 as a BackGround Electrolyte (BGE) by using an uncoated fused silica capillary of I.D. = 50 mm and applying a voltage of 25 kV in the first part of the electropheretic run (up to 5.8 min) and 30 kV for the remaining time. The hydrodynamic pressurization of the inlet vial was 20 psi at 7.2 min. up to the end of analysis. Total separation time was of 7.5 min. The method was then successfully validated and applied to the simultaneous determination of active ingredients and preservatives. Good repeatability, linearity, and sensitivity were demonstrated. Precision of migration time (tm) was RSD% < 0.53% and of corrected peak area (Ac) was RSD% < 6.15%. The linearity evaluation gave 0.9928 2 1.000. LOD and LOQ, accuracy (recovery) and ruggedness were evaluated for each analyte demonstrating the good reliability of the method. Analyses of some pharmaceutical real samples were performed.

Paraben Content in Adjacent Normal-malignant Breast Tissues from Women with Breast Cancer

Objective Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life.To assess the role of parabens in this phenomenon,the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province,Iran.Methods Adjacent normal-malignant breast tissue samples were obtained from 53 subjects.The parabens including methyl-paraben(Me PB),ethyl-paraben(Et PB),propyl-paraben(Pr PB),and butylparaben(Bu PB)were extracted from the sample supernatant and then subjected to gas chromatography analysis.Results Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer.We observed a significant association for dose-response pattern of Me PB[OR=98.34(11.43–185.2),P=0.027]for both ER+and PR+women and Me PB[OR=164.3(CI:112.3–216.3),P<0.001]for HER2+women than women with negative receptors.The risk of 95-fold increase in Me PB dose and 164-fold increase in∑PBs dose were significant for women with hereditary breast cancer in first-degree relatives.Conclusions These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.

Simple HPLC Analysis of Hinokitiol in Skin Lotion with Visible Light Detection after Pre-Column Dabsylation

Hinokitiolis frequently added to personal care products as an antibacterial agent. We previously established an HPLC-UV method for determination of hinokitiol in skin lotion after pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole. However, the labeling reagent is expensive, and derivatives of degradation products of parabens, which may be added to skin lotion as general preservatives, interfered with the peak of the hinokitiol derivative. In this study, the concentration of hinokitiol in skin lotions was determined by HPLC with a visible light detector (450 nm) after pre-column derivatization with 4-(dimethylamino)azobenzene-4’-sulfonyl chloride (Dabsyl-Cl), a more economical reagent. A standard curve was obtained after derivatization with Dabsyl-Cl in borate buffer (pH 9.5) at 55&deg;C for 10 min. The retention time of Dabsyl-hinokitiol was 6.8 min. The calibration plot was linear in the range of 1.25 to 40 μg/mL with a r2 value of 0.9991, and the lower limit of quantification and detection were 0.60 μg/mL (absolute amount of 0.86 ng/20μL injection, signal-to-noise ratio of 10:1) and 0.18 μg/mL (absolute amount of 0.26 ng/20μL injection, signal-to-noise ratio of 3:1), respectively. The coefficient of variation was less than 8.8%. Seven Dabsyl-paraben derivatives showed little interference with the peak of Dabsyl-hinokitiol. The developed system was used to determine the content of hinokitiol in two skin lotions. Addition-recovery tests gave satisfactory results.

Remediation of preservative ethylparaben in water using natural sphalerite:Kinetics and mechanisms

As a typical class of emerging organic contaminants(EOCs), the environmental transformation and abatement of preservative parabens have raised certain environmental concerns. However, the remediation of parabens-contaminated water using natural matrixes(such as, naturally abundant minerals) is not reported extensively in literature. In this study, the transformation kinetics and the mechanism of ethylparaben using natural sphalerite(NS) were investigated. The results show that around 63% of ethylparaben could be absorbed onto NS within 38 hr, whereas the maximum adsorption capacity was 0.45 mg/g under room temperature. High temperature could improve the adsorption performance of ethylparaben using NS. In particular, for the temperature of 313 K, the adsorption turned spontaneous. The well-fitted adsorption kinetics indicated that both the surface adsorption and intra-particle diffusion contribute to the overall adsorption process. The monolayer adsorption on the surface of NS was primarily responsible for the elimination of ethylparaben. The adsorption mechanism showed that hydrophobic partitioning into organic matter could largely govern the adsorption process, rather than the Zn S that was the main component of NS. Furthermore, the ethylparaben adsorbed on the surface of NS was stable, as only less than 2% was desorbed and photochemically degraded under irradiation of simulated sunlight for 5 days. This study revealed that NS might serve as a potential natural remediation agent for some hydrophobic EOCs including parabens, and emphasized the significant role of naturally abundant minerals on the remediation of EOCs-contaminated water bodies.

Fabrication of the Metal-Organic Framework Membrane with Excellent Adsorption Properties for Paraben Based on Micro Fibrillated Cellulose

A kind of novel environmental-friendly composite absorbent material was designed and prepared in this paper.Nanoscale metal-organic frameworks(MOFs)were embedded in the skeleton of cotton micro fibrillated cellulose.By scanning electron microscope(SEM),we observed that a large number of MOFs were attached to the cellulose skeleton.In addition,under the condition of 1800 r/min vortex,the structure of the composite material was stable and was not easily damaged by external forces.The water contact angle test showed that the composite material had excellent hydrophilicity and could be used for the adsorption of pollutants.Then,the material was characterized by energy dispersive X-ray spectroscopy(EDX),X-ray diffraction(XRD),Fourier transform infrared spectroscopy(FTIR)and BET adsorption.Through verification,the material had very stable reusability(n=10).The composite material was applied to the solid phase extraction of water samples,such as rain water,toning water and fruit juice,and was quantitatively analyzed by high performance liquid chromatography(HPLC)-UV.This method was then applied to the extraction of four parabens(methyl-,ethyl-,propyl-,and butylparaben)from real samples,yielding limits of detection(LODs)of 0.29-0.58 ng/mL.The linear range was 2-500 ng/mL.The inter-day and intra-day recoveries were 90.7%-106.0%and 87.1%-109.3%,respectively(relative standard deviation<10.8%).

The potential for estrogen disrupting chemicals to contribute to migration, invasion and metastasis of human breast cancer cells

Estrogen disrupting chemicals are environmental compounds which mimic, antagonize or interfere in the action of physiological estrogens. They occur naturally (plant phytoestrogens) but the majority are man-made compounds, which, through their use in agricultural, industrial and consumer products, have become widely present in human tissues including breast tissue. Since exposure to estrogen is a risk factor for breast cancer, estrogen disrupting chemicals may also contribute to breast cancer development. This review discusses evidence implicating estrogen disrupting chemicals in increasing migratory and invasive activity of breast epithelial cells, in epithelial-to-mesenchymal transition, and in growth of breast tumours at metastatic sites as well as the primary site. Mechanisms may be through the ability of such chemicals to bind to estrogen receptors, but unlike for proliferation, effects on cell migration and invasion are not limited to estrogen receptor-mediated mechanisms. Furthermore, whilst effects on proliferation can be measured within hours/days of adding an estrogen disrupting chemical to estrogen-responsive breast cancer cells, effects on cell migration occur after longer times (weeks). Most studies have focused on individual chemicals, but there is now a need to consider the environmentally relevant effects of long-term, low-dose exposure to complex mixtures of estrogen disrupting chemicals on mechanisms of metastasis.