Concentrations, compositional profiles, and health risks of benzophenones among the Taiwanese population based on analysis of 23 daily consumed foods.

In this study, we analyzed the occurrence and distribution of 11 benzophenone-type ultraviolet filters (BPs) in 893 food samples spanning 7 food categories in Taiwan. We conducted a Monte Carlo simulation to determine the carcinogenic and noncarcinogenic risks of BPs. The results indicated that cornflakes had the highest mean level of BPs (103 ng/g), followed by bread (101 ng/g) and pastries (59 ng/g). BP was the most prevalent category, followed by 4-methylbenzophenone (4-MBP), 2-hydroxybenzophenone, and benzophenone-3. Estimation of the lifetime cancer risk (LTCR) of BP (average life expectancy of 80 years) placed them in the 50th and 97.5th percentiles [P50 (P97.5)] LTCR of 1.9 × 10-7 (5.7 × 10-6), indicating that BP in food poses a low renal hazard to the Taiwanese population. The noncarcinogenic risk of BPs was evaluated using a hazard quotient and combined margin of exposure (MOET), revealing a P50 (P97.5) hazard index of < 1 for BP, 4-MBP, and methyl-2-benzoylbenzoate. Although the P50 MOET values for all age groups were within the moderate range of concern, with a more conservative extreme (P2.5), the MOET values for the 0-3, 3-6, and 6-12 age groups fell below 100, indicating a high concern for renal degeneration and hyperplasia.

A multiplex approach of MS, 1D-, and 2D-NMR metabolomics in plant ontogeny: A case study on Clusia minor L. organs (leaf, flower, fruit, and seed).

INTRODUCTION: The genus Clusia L. is mostly recognised for the production of prenylated benzophenones and tocotrienol derivatives. OBJECTIVES: The objective of this study was to map metabolome variation within Clusia minor organs at different developmental stages. MATERIAL AND METHODS: In total 15 organs/stages (leaf, flower, fruit, and seed) were analysed by UPLC-MS and 1H- and heteronuclear multiple-bond correlation (HMBC)-NMR-based metabolomics. RESULTS: This work led to the assignment of 46 metabolites, belonging to organic acids(1), sugars(2) phenolic acids(1), flavonoids(3) prenylated xanthones(1) benzophenones(4) and tocotrienols(2). Multivariate data analyses explained the variability and classification of samples, highlighting chemical markers that discriminate each organ/stage. Leaves were found to be rich in 5-hydroxy-8-methyltocotrienol (8.5 µg/mg f.w.), while flowers were abundant in the polyprenylated benzophenone nemorosone with maximum level detected in the fully mature flower bud (43 µg/mg f.w.). Nemorosone and 5-hydroxy tocotrienoloic acid were isolated from FL6 for full structural characterisation. This is the first report of the NMR assignments of 5-hydroxy tocotrienoloic acid, and its maximum level was detected in the mature fruit at 50 µg/mg f.w. Seeds as typical storage organ were rich in sugars and omega-6 fatty acids. CONCLUSION: To the best of our knowledge, this is the first report on a comparative 1D-/2D-NMR approach to assess compositional differences in ontogeny studies compared with LC-MS exemplified by Clusia organs. Results derived from this study provide better understanding of the stages at which maximal production of natural compounds occur and elucidate in which developmental stages the enzymes responsible for the production of such metabolites are preferentially expressed.

Dietary risk assessment of benzophenone derivatives using bread consumption estimates in a Taiwanese population.

Listed as endocrine-disrupting chemicals, benzophenone (BP) and its nine analogues (BPs) are an emerging group of contaminants. The migration of BPs from ultraviolet inks to food has been investigated in many studies; however, few studies have investigated BPs in foods and the risks of human exposure to BPs. We validated a trace and multi-residue method for simultaneously determining 10 BPs, including BP, BP-1, BP-2, BP-3, BP-8, 4-MBP, 2-OHBP, 4-OHBP, M2BB, and PBZ. Eighty-one bread samples were analyzed using stable isotope labeling and ultrahigh-performance liquid chromatography-electrospray ionization tandem mass spectrometry with solid-liquid extraction. We determined the estimated daily intake of BPs, non-cancer risks, and lifetime cancer risks (LTCRs) from daily bread consumption for seven age groups using a Monte Carlo simulation. The method demonstrated robust linearity (R2 ≥ 0.991), low limits of detection (0.04-2 ng/g), and satisfactory precision. The intra- and interday relative standard deviation ranges were 0.6%-9% and 3%-20%, respectively. BP, 4-MBP, 2-OHBP, BP-1, and BP-3 were detected in 97%, 67%, 59%, 24%, and 23% of the samples, respectively. 2-OHBP had the highest mean (range) value of 18.3 (

Benzophenone-3: Comprehensive review of the toxicological and human evidence with meta-analysis of human biomonitoring studies.

BACKGROUND: Benzophenone-3 (BP-3) and its major metabolite benzophenone-1 (BP-1) are widely used as UV filters in sunscreens and cosmetics to prevent sunburn and skin damage, or as stabilizers to prevent photodegradation in many commercial products. As a result, their presence is ubiquitous in the environment, wildlife and humans. Based on endocrine disruption concerns, international regulatory agencies are performing a closer evaluation. OBJECTIVE AND METHODS: This work aimed to comprehensively review the available human relevant evidence for safety issues in MEDLINE/PubMed in order to create a structured database of studies, as well as to conduct an integrative analysis as part of the Human Biomonitoring for Europe (HBM4EU) Initiative. RESULTS: A total of 1,635 titles and abstracts were screened and 254 references were evaluated and tabulated in detail, and classified in different categories: i) exposure sources and predictors; ii) human biomonitoring (HBM) exposure levels to perform a meta-analysis; iii) toxicokinetic data in both experimental animals and humans; iv) in vitro and in vivo rodent toxicity studies; and v) human data on effect biomarkers and health outcomes. Our integrative analysis showed that internal peak BP-3 concentrations achieved after a single whole-body application of a commercially available sunscreen (4% w/w) may overlap with concentrations eliciting endocrine disrupting effects in vitro, and with internal concentrations causing in vivo adverse female reproductive effects in rodents that were supported by still limited human data. The adverse effects in rodents included prolonged estrous cycle, altered uterine estrogen receptor gene expression, endometrium hyperplasia and altered proliferation and histology of the mammary gland, while human data indicated menstrual cycle hormonal alterations and increased risk of uterine fibroids and endometriosis. Among the modes of action reported (estrogenic, anti-androgenic, thyroid, etc.), BP-3 and especially BP-1 showed estrogenic activity at human-relevant concentrations, in agreement with the observed alterations in female reproductive endpoints. The meta-analysis of HBM studies identified a higher concern for North Americans, showing urinary BP-3 concentrations on average 10 and 20 times higher than European and Asian populations, respectively. DISCUSSION AND CONCLUSIONS: Our work supports that these benzophenones present endocrine disrupting properties, endorsing recent European regulatory efforts to limit human exposure. The reproducible and comprehensive database generated may constitute a point of departure in future risk assessments to support regulatory initiatives. Meanwhile, individuals should not refrain from sunscreen use. Commercially available formulations using inorganic UV filters that are practically not absorbed into systemic circulation may be recommended to susceptible populations.

Fish consumption is an indicator of exposure to benzophenone derivatives: A probabilistic risk assessment in Taiwanese population.

Benzophenone (BP) derivatives (BPs) ultraviolet filters are used in industrial and commercial products and have been reported to be toxic. Studies have investigated the ecological risks but not the human exposure risks of BPs. Residues of 10 BPs (BP, BP-1, BP-2, BP-3, BP-8, 2-OHBP, 4-OHBP, 4-MBP, M2BB, and PBZ) were measured in 110 commercial samples of saltwater fish (SF) and freshwater fish (FF) from Taiwan. The estimated daily intakes (EDIs) and noncarcinogenic risks (as hazard quotients [HQs] and hazard indices [HIs]) were predicted for eight age groups by using Monte Carlo simulation, and sensitivity analysis was conducted to determine the factors influencing risks. The carcinogenic risk of exposure to BP was estimated using lifetime cancer risk (LTCR). The results revealed that seven BPs (BP, BP-3, 2-OHBP, 4-OHBP, 4-MBP, PBZ, and M2BB) were ubiquitous in the fish samples. The mean sums of the content of these seven BPs in FF and SF were 46.4 ng/g and 25.0 ng/g, respectively. Infants (age 0-3 years) exhibited the highest HI of BPs (1.6E-2) and LTCR of BP (2.8E-7) among all age groups. The HQs and HIs of all BPs were less than 1 and the LTCR for BP was lower than the acceptable range (10-4 to10-6) in all age groups, suggesting that BPs intake through fish consumption is not a health concern for Taiwanese people. The results of the sensitivity analysis demonstrated that the amount of SF consumed and 2-OHBP levels exerted the greatest effect on risk. Considering the relatively higher risk of fish consumption and concerns that ultraviolet filters are endocrine disruptors, the potential health risks of BPs intake for infants deserves further attention.

Determination of bisphenols, parabens, and benzophenones in placenta by dispersive liquid-liquid microextraction and gas chromatography-tandem mass spectrometry.

Human exposure to endocrine disrupting chemicals (EDCs) is of particular concern during development. Bisphenols, parabens, and benzophenones are EDCs widely used in the manufacture of numerous goods, personal care products, and cosmetics. The aim of this study was to develop a new and practical method for determining three bisphenols, four parabens, and five benzophenones in placenta samples. It uses dispersive liquid-liquid microextraction (DLLME) in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS). Several chemometric approaches were employed to optimize the experimental parameters. Limits of detection ranged from 0.04 to 0.08 ng g-1 and inter-day variabilities (evaluated as relative standard deviation) from 4.2% to 13.4%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery percentages ranged from 87.1% to 113.2%. Finally, the method was used to measure target compounds in 20 placental tissue samples from voluntary donors. This analytical procedure can provide information on the exposure of the fetus to non-persistent EDCs.

Multivariate optimization of low-temperature cleanup followed by dispersive solid-phase extraction for detection of Bisphenol A and benzophenones in infant formula.

A simple and effective analytical method to determine six contaminants, including five benzophenones (BP, BP-1, BP-3, BP-8, and BP-12) and bisphenol A (BPA) in infant formulas was developed in this study. For this, a sequential experimental design was used to optimize the extraction and cleanup method using low temperature partition (LTP) combined with dispersive solid phase extraction (dSPE). The effect of primary secondary amine (PSA), sodium chloride (NaCl), graphitized carbon black (GCB), octadecyl (C18), strong anion exchanger (SAX), water, acetonitrile (ACN) and, ultrasound (US) time were evaluated using a sequential design of experiments including a Plackett-Burman, a central composite rotatable design, and the Derringer and Suich's tool. The method was validated, and it showed a limit of quantification varying from 0.06 to 2 mg.kg-1, good precision (< 20% RSD), and recovery (52-106%). The method proposed was applied to twenty-five samples of commercial infant formulas.

Selection of calibration compounds for selectivity evaluation of wall-coated, open-tubular columns for gas chromatography by the solvation parameter model.

To facilitate faster selectivity evaluation of wall-coated, open-tubular columns using the solvation parameter model a reduced set of calibration compounds is identified and validated for the temperature ranges 60-140 °C and 160-260 °C. The Kennard-Stone uniform mapping algorithm is used to identify the calibration compounds from a larger database of compounds with known retention properties previously adopted for column selectivity evaluation. Thirty-five compounds for each temperature range are required to minimize the standard deviation of the system constants used for selectivity evaluation and to minimize differences between system constants determined by conventional calibration and the reduced calibration compounds. The models for the reduced calibration compounds on ten siloxane-based and poly(ethylene glycol) stationary phases have a coefficient of determination of 0.984 to 0.998 and standard error of the estimate of 0.012 to 0.30. The predictive capability of models is evaluated for the reduced sets of calibration compounds using external test sets with ranking of the calibration models by changes in the average error, average absolute error and root mean square error of prediction for the test sets. For the selected thirty-five reduced calibration compounds the range for the average absolute error was 0.014 to 0.033 and 0.016 to 0.040 for the root mean square error of prediction for the independent test sets.

Dalbergia ecastaphyllum (L.) Taub. and Symphonia globulifera L.f.: The Botanical Sources of Isoflavonoids and Benzophenones in Brazilian Red Propolis.

The Brazilian red propolis (BRP) constitutes an important commercial asset for northeast Brazilian beekeepers. The role of Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) as the main botanical source of this propolis has been previously confirmed. However, in addition to isoflavonoids and other phenolics, which are present in the resin of D. ecastaphyllum, samples of BRP are reported to contain substantial amounts of polyprenylated benzophenones, whose botanical source was unknown. Therefore, field surveys, phytochemical and chromatographic analyses were undertaken to confirm the botanical sources of the red propolis produced in apiaries located in Canavieiras, Bahia, Brazil. The results confirmed D. ecastaphyllum as the botanical source of liquiritigenin (1), isoliquiritigenin (2), formononetin (3), vestitol (4), neovestitol (5), medicarpin (6), and 7-O-neovestitol (7), while Symphonia globulifera L.f. (Clusiaceae) is herein reported for the first time as the botanical source of polyprenylated benzophenones, mainly guttiferone E (8) and oblongifolin B (9), as well as the triterpenoids ß-amyrin (10) and glutinol (11). The chemotaxonomic and economic significance of the occurrence of polyprenylated benzophenones in red propolis is discussed.

Analytical methodology to screen UV-filters and synthetic musk compounds in market tomatoes.

A Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) methodology followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis was developed to extract thirteen synthetic musk compounds (SMCs: cashmeran, celestolide, phantolide, traseolide, galaxolide, tonalide, musk ambrette, musk xylene, musk ketone, musk tibetene, musk moskene, ethylene brassylate and exaltolide) and six ultraviolet-filters (UVFs: 2-ethylhexyl 4-dimethylaminobenzoate, 3-(4'-methylbenzylidene) camphor, 2-ethylhexyl 4-methoxycinnamate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, benzophenone and drometrizole trisiloxane) from tomatoes. The proposed methodology was optimized: 2 g of freeze-dried tomato was extracted with 4 mL of water and 10 mL of ethyl acetate, adding 6 g of MgSO4 and 1.5 g of NaCl, then a dispersive solid-phase extraction was performed using 3 g of MgSO4, 300 mg of primary-secondary amino adsorbent (PSA) and 300 mg of octadecyl-silica (C18). Validation delivered recoveries between 81 (celestolide) and 119% (musk tibetene), with relative standard deviations <10%. The instrumental limit of detection varied from 0.02 (2-ethylhexyl 4-methoxycinnamate) to 3.00 pg (exaltolide and musk xylene). Regarding the method quantification limits, it ranged between 0.4 (celestolide) and 47.9 ng g-1 dw (exaltolide). The method was applied to different varieties of tomatoes (Solanum lycopersicum), revealing UVFs and SMCs between 1 and 210 ng g-1 dw. Higher concentrations were found for benzophenone (29-210 ng g-1 dw) and galaxolide (9-53 ng g-1 dw). The risk associated to the ingestion of contaminated tomatoes has also been estimated, showing that a potential health risk is unlikely.

Comparative study of ink photoinitiators in food packages using gas chromatography with vacuum ultraviolet detection and gas chromatography with mass spectrometry.

This work focused on the development and validation of the analytical procedure using gas chromatography equipped with vacuum-ultraviolet detection for the specific and sensitive determination of nine photoinitiators in food packages. Subsequently, a comparison of the combination of vacuum ultraviolet spectroscopy with gas chromatography and a developed gas chromatography with mass spectrometry method was performed. The vacuum-ultraviolet spectra of all tested photoinitiators were collected and found to be highly distinct, even for isomers. Under the optimal conditions, the limits of detection for nine photoinitiators ranged from 1 to 5 mg/L using vacuum ultraviolet detection and from 0.15 to 0.5 mg/L using mass spectrometric detection. Both techniques were successfully applied for screening of photoinitiators in seven kinds of food packages and the obtained data showed good agreement (the relative difference was between 3 and 18%). The variability in concentrations found in triplicate samples was assessed to be below 18%. Predominantly benzophenone was found in all analysed samples in the range of 0.31-4.23 mg/kg. It appears to be preferably selected by food packaging manufacturers. This study proposes a new simple and sensitive technique used for analysis of photoinitiators that could be a good alternative to gas chromatography with mass spectrometry.

Optimization of solid-phase extraction of parabens and benzophenones in water samples using a combination of Plakett-Burman and Box-Behnken designs.

An automated method for the analysis of methylparaben, propylparaben, benzophenone-3, and benzophenone-4 in water effluents via on-line solid-phase extraction coupled with high-performance liquid chromatography/ultraviolet detection was proposed. The preconcentration parameters were studied using Plackett-Burman and Box-Behnken experimental designs using a C18 sorbent material. The results demonstrated that the eluent volume, composition, and sorbent amount were statistically significant. Optimal conditions for these variables were an eluent volume of 1.55 mL, eluent composition of acetonitrile 100% v/v, and sorbent amount of 100 mg. The eluted sample was analyzed on-line using high-performance liquid chromatography equipped with a reversed-phase C18 column and ultraviolet detection. Separation of the analytes was achieved in 15 min using gradient elution with acetonitrile/water. A simple, sensitive, and rapid analytical method was proposed for personal care compounds without sophisticated or expensive equipment. The limits of detection were 1.20, 1.73, 2.51, and 4.67 µg/L for propylparaben, methylparaben, benzophenone-3, and benzophenone-4, respectively. The analysis time was 48 min, consuming only 1.59 mL of eluent acetonitrile for the solid phase extraction step, with minimal sample handling. The method was applied to the analysis of spiked swimming pool and wastewater, with recoveries between 65-107%. These results indicate the reliability of the flow-based procedure.

Measurement of concentrations of four chemical ultraviolet filters in human breast tissue at serial locations across the breast.

The human population is widely exposed to benzophenone-3 (BP-3), octylmethoxycinnamate (OMC), 4-methylbenzilidenecamphor (4-MBC) and homosalate from their use in consumer goods to absorb ultraviolet (UV) light. Their oestrogenic activity and presence in human milk suggest a potential to influence breast cancer development. In this study, high-performance liquid chromatography-tandem mass spectrometry was used to measure concentrations of these UV filters in human breast tissue from three serial locations across the breast from 40 women undergoing mastectomy for primary breast cancer. One or more of these UV filters were quantifiable in 101 of 120 (84%) of the tissue samples and at least one breast region for 38 of 40 women. BP-3 was measured in 83 of 120 (69%) tissue samples and at least one breast region for 33 of 40 women (range 0-26.0 ng g-1 tissue). OMC was measured in 89 of 120 (74%) tissue samples and at least one breast region for 33 of 40 women (range 0-58.7 ng g-1 tissue). 4-MBC was measured in 15 of 120 (13%) tissue samples and at least one breast region for seven of 40 women (range 0-25.6 ng g-1 tissue). Homosalate was not detected in any sample. Spearman's analyses showed significant positive correlations between concentrations of BP-3 and OMC in each of the three breast regions. For ethical reasons cancerous tissue was not available, but as the location of the cancer was known, Mann-Whitney U-tests investigated any link between chemical concentration and whether a tumour was present in that region or not. For the lateral region, more BP-3 was measured when a tumour was present (P = .007) and for OMC the P value was .061. For seven (of 40) women with measurable 4-MBC, six of seven had measurable 4-MBC at the site of the tumour.

Bromfenac ophthalmic solution 0.09 %: human aqueous humor concentration detected by high-performance liquid chromatography.

The purpose of this study was to evaluate the aqueous humor concentrations of bromfenac ophthalmic solution 0.09 % in patients undergoing phacoemulsification. Patients requiring cataract extraction received one drop (50 µL) of bromfenac 0.09 % solution in the eye to be operated, before bedtime the day before surgery or the morning of the surgery. The last administration was recorded. At the time of paracentesis, an aqueous humor sample was collected with a 30-gauge needle attached to a TB syringe and was later analyzed by high-performance liquid chromatography for drug concentration. 188 treated volunteers and 48 control, untreated, subjects were included in the study. The mean aqueous concentration of bromfenac in the treated group was 37.60 ± 68.86 and 0 nM (nmol/L) in the control group (p < 0.0001). Correlation coefficient in bromfenac group between time elapsed from instillation and drug concentration was -0.16 (p not significant). Bromfenac showed properties of good penetration and stable concentration in aqueous humor up to about 12 h after instillation.

Urinary arsenic, pesticides, heavy metals, phthalates, polyaromatic hydrocarbons, and polyfluoroalkyl compounds are associated with sleep troubles in adults: USA NHANES, 2005-2006.

Links between environmental chemicals and human health have emerged, but the effects on sleep health were less studied. Therefore, the aim of the present study was to investigate the relationships of different sets of environmental chemicals and common sleep troubles in a national and population-based setting. Data were retrieved from the United States National Health and Nutrition Examination Surveys, 2005-2006 including demographics, serum measurements, lifestyle factors, self-reported sleep troubles, and urinary environmental chemical concentrations. Statistical analyses including descriptive statistics, t-test, chi-square test, and survey-weighted logistic regression models were performed. Of all 5563 Americans aged 18-85, 2331 (42.0%) had wake-up at night, 2914 (52.5%) felt unrested during the day, 740 (13.4%) had leg jerks while sleeping, and 1059 (19.1%) had leg cramps for 2+ times a month. Higher levels of urinary arsenic, phthalates, and polyfluoroalkyl compounds were associated with wake-up at night. Higher levels of urinary 4-tert-octylphenol and polyfluoroalkyl compounds were associated with being unrested during the day. Higher levels of urinary arsenic, polyaromatic hydrocarbons, and polyfluoroalkyl compounds were associated with leg jerks while sleeping. Higher levels of urinary pesticides, heavy metals, phthalates, and polyaromatic hydrocarbons were associated with leg cramps while sleeping. However, there were no significant associations with other environmental chemicals such as parabens, bisphenol A, benzophenone-3, triclosan, perchlorate, nitrate, or thiocyanate. Eliminating arsenic, heavy metals, phthalate, pesticides, polyaromatic hydrocarbons, and polyfluoroalkyl compounds to improve sleep health might be considered while understanding the biological pathway with a longitudinal or experimental approach in future research would be suggested.

Simultaneous determination of cosmetics ingredients in nail products by fast gas chromatography with tandem mass spectrometry.

A rapid and sensitive gas chromatography with tandem mass spectrometry (GC-MS/MS) method has been developed and validated to quantitatively determine cosmetic ingredients, such as toluene, N-methylpyrrolidone, 2,4-dihydroxybenzophenone (benzophenone-1, BP-1), and diethylene glycol dimethacrylate, in nail products. In this procedure, test portions were extracted with acetone, followed by vortexing, sonication, centrifugation, and filtration. During the extraction procedure, BP-1 was derivatized making it amenable to GC-MS analysis, using N,O-​bis(trimethylsilyl)​trifluoroacetamide. The four ingredients were quantified by GC-MS/MS in an electron ionization mode. Four corresponding stable isotopically labeled analogues were selected as internal standards, which were added at the beginning of the sample preparation to correct for recoveries and matrix effects. The validated method was used to screen 34 commercial nail products for these four cosmetic ingredients. The most common ingredients detected in the nail products were toluene and BP-1. Toluene was detected in 26 products and ranged from 1.36 to 173,000µg/g. BP-1 ranged from 18.3 to 2,370µg/g in 10 products.

Simultaneous Determination of 10 Photoinitiators in Milk by Solid-Phase Microextraction Coupled with Gas Chromatography/Mass Spectrometry.

Photoinitiators (PIs) are widely used in food packaging materials, can migrate easily from packaging materials to food, and cause food contamination. It is essential to establish a method of determining PIs residues in food. A new method for simultaneously determining 10 kinds of PIs in milk has been established by using solid-phase microextraction (SPME) combined with a simple method of protein precipitation as the pretreatment approach and gas chromatography/mass spectrometry as the detecting technique. The limits of detection for 10 PIs in different milks were between 0.05 and 1.4 µg/L (skimmed milk), between 0.07 and 2.2 µg/L (semi-skimmed milk), between 0.11 and 4.4 µg/L (whole milk), respectively. The recoveries were from 71.5% to 133.5%, and the relative standard deviations were less than 15%. Twelve kinds of packed milk with different brands and fat contents were determined using this method.

Determination of benzophenones in lipophilic extract of Brazilian red propolis, nanotechnology-based product and porcine skin and mucosa: Analytical and bioanalytical assays.

Lipophilic compounds of Brazilian Red Propolis (BRP) have received increasing attention due to some interesting findings regarding their biological activities. This study was first aimed at evaluating the chemical composition of BRP n-hexane extract (HEXred) by UPLC-MS-PDA. Chemical investigation mainly resulted in the identification of polyprenylated benzophenones (PPBs) in this extract, named oblongifolin A, guttiferone E, and/or xanthochymol. After that, an isocratic HPLC-UV method was validated for the determination of total content of PPBs (at 260 nm) expressed as garcinol, a commercially available guttiferone E diastereoisomer. The method showed to be specific, precise, accurate, and linear (0.1-10 µg/mL) for the determination of PPBs in HEXred, BRP-loaded nanoemulsions, as well as, in porcine skin and mucosa samples after permeation/retention studies. The matrix effect was determined for all complex matrices, demonstrating low effect during the analysis. The stability-indicating method was verified by submitting HEXred to acidic, alkaline, oxidative, and thermal stress conditions. No interference of degradation products was detected during analysis. Therefore, the proposed analytical and bioanalytical methods proved to be simple and reliable for the determination of PPBs in the presence of different matrices.

In-cell clean-up pressurized liquid extraction and gas chromatography-tandem mass spectrometry determination of hydrophobic persistent and emerging organic pollutants in coastal sediments.

The main goal of this work was to develop, optimize and validate a multi-residue method for the simultaneous determination of 97 contaminants, including fragrances, UV filters, repellents, endocrine disruptors, biocides, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organophosphorus flame retardants, and several types of pesticides in marine sediment samples. Extraction and cleanup were integrated into the same step using pressurized liquid extraction (PLE) with in-cell clean-up (1g of alumina). The extraction was performed using dichloromethane at 100 °C, 1500 psi and 3 extraction cycles (5 min per cycle). Extracts were derivatized with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA) to improve the signal and sensitivity of some target compounds (i.e., triclosan, 2-hydroxybenzophenone). Separation, identification and quantification of analytes were carried out by gas chromatography (GC) coupled to tandem mass spectrometry. Under optimal conditions, the optimized protocol showed good recovery percentages (70-100%), linearity (>0.99) and limits of detection below 1 ng g(-1) for all compounds. Finally, the method was applied to the analysis of sediment samples from different coastal areas from Andalusia (Spain), where occurrence and distribution of emerging contaminants in sediments is very scarce. Twenty five compounds out of 98 were detected in all samples, with the endocrine disruptor nonylphenol and the fragrance galaxolide showing the highest concentrations, up to 377.6 ng g(-1) and 237.4 ng g(-1), respectively.

Determination of benzophenone-UV filters in human milk samples using ultrasound-assisted extraction and clean-up with dispersive sorbents followed by UHPLC-MS/MS analysis.

A new sample preparation method for the determination of five benzophenone UV-filters in human breast milk has been developed. The procedure involves the lyophilization of the sample, and its subsequent extraction by ultrasound sonication using acetonitrile. In order to reduce matrix effects produced by milk components that are coextracted, mainly proteins, sugars and lipids, a further clean-up step with a mixture of dispersive-SPE sorbents, C18 and PSA, was applied. Extraction parameters were optimized using experimental design, and the compounds were detected and quantified by ultrahigh performance liquid-chromatography tandem mass spectrometry (UHPLC-MS/MS) in positive ESI mode. Analytes were separated in 10 min. BP-d10 was used as internal standard. The limits of detection (LODs) were between 0.1 and 0.2 ng mL(-1), and the limits of quantification (LOQs) were between 0.3 and 0.6 ng mL(-1) for the target analytes. The inter- and intra-day variability was <12%. The method was validated using matrix-matched calibration and recovery assays with spiked samples. Recovery rates were between 90.9 and 109.5%. The method was successfully applied for the determination of these compounds in human milk samples collected from volunteers lactating mothers with no known occupational exposure to these compounds who live in the province of Granada (Spain). The analytical method developed here may be useful for the development of more in-depth studies on the prenatal exposure and biomonitoring of these commonly used UV-filters.