Science.gov

Sample records for methylparaben ethylparaben propylparaben

  1. A New Validated HPLC Method for the Simultaneous Determination of 2-phenoxyethanol, Methylparaben, Ethylparaben and Propylparaben in a Pharmaceutical Gel

    PubMed Central

    Shabir, G. A.

    2010-01-01

    A novel reversed-phase HPLC method has been developed and validated for the simultaneous determination of 2-phenoxyethanol, methylparaben, ethylparaben and propylparaben preservatives. The method uses a Lichrosorb C8 (150×4.6 mm, 5 µm) column and isocratic elution. The mobile phase consisted of a mixture of acetonitrile, tetrahydrofuran and water (21:13:66, v/v/v), pumped at a flow rate of 1 ml/min. The UV detection was set at 258 nm. The method was validated with respect to accuracy, precision (repeatability and intermediate precision), specificity, linearity and range. All the parameters examined met the current recommendations for bioanalytical method validation. The developed method was successfully applied to the determination of commercially available pharmaceutical gel products for these preservatives. The procedure describes here is simple, selective and reliable for routine quality control analysis and stability tests. PMID:21218050

  2. A New Validated HPLC Method for the Simultaneous Determination of 2-phenoxyethanol, Methylparaben, Ethylparaben and Propylparaben in a Pharmaceutical Gel.

    PubMed

    Shabir, G A

    2010-07-01

    A novel reversed-phase HPLC method has been developed and validated for the simultaneous determination of 2-phenoxyethanol, methylparaben, ethylparaben and propylparaben preservatives. The method uses a Lichrosorb C8 (150×4.6 mm, 5 µm) column and isocratic elution. The mobile phase consisted of a mixture of acetonitrile, tetrahydrofuran and water (21:13:66, v/v/v), pumped at a flow rate of 1 ml/min. The UV detection was set at 258 nm. The method was validated with respect to accuracy, precision (repeatability and intermediate precision), specificity, linearity and range. All the parameters examined met the current recommendations for bioanalytical method validation. The developed method was successfully applied to the determination of commercially available pharmaceutical gel products for these preservatives. The procedure describes here is simple, selective and reliable for routine quality control analysis and stability tests. PMID:21218050

  3. The estrogenicity of methylparaben and ethylparaben at doses close to the acceptable daily intake in immature Sprague-Dawley rats

    PubMed Central

    Sun, Libei; Yu, Tong; Guo, Jilong; Zhang, Zhaobin; Hu, Ying; Xiao, Xuan; Sun, Yingli; Xiao, Han; Li, Junyu; Zhu, Desheng; Sai, Linlin; Li, Jun

    2016-01-01

    The estrogenicity of parabens at human exposure levels has become a focus of concern due to the debate over whether the estrogenicity of parabens is strong enough to play a role in the increased incidence of breast cancer. In this study, the uterotrophic activities of methylparaben (MP) and ethylparaben (EP) at doses close to the acceptable daily intake as allocated by JECFA were demonstrated in immature Sprague-Dawley rats by intragastric administration, and up-regulations of estrogen-responsive biomarker genes were found in uteri of the rats by quantitative real-time RT–PCR (Q-RT-PCR). At the same time, the urinary concentrations of MP and EP, as measured by gas chromatography–mass spectrometry (GC-MS) in rats that received the same doses of MP and EP, were found to be near the high urinary levels reported in human populations in recent years. These results show the in vivo estrogenicity of MP and EP at human exposure levels, and indicate that populations exposed to large amounts of MP and EP may have a high burden of estrogenicity-related diseases. In addition, a molecular docking simulation showed interaction between the parabens and the agonist-binding pocket of human estrogen receptor α (hERα). PMID:27121550

  4. The estrogenicity of methylparaben and ethylparaben at doses close to the acceptable daily intake in immature Sprague-Dawley rats.

    PubMed

    Sun, Libei; Yu, Tong; Guo, Jilong; Zhang, Zhaobin; Hu, Ying; Xiao, Xuan; Sun, Yingli; Xiao, Han; Li, Junyu; Zhu, Desheng; Sai, Linlin; Li, Jun

    2016-01-01

    The estrogenicity of parabens at human exposure levels has become a focus of concern due to the debate over whether the estrogenicity of parabens is strong enough to play a role in the increased incidence of breast cancer. In this study, the uterotrophic activities of methylparaben (MP) and ethylparaben (EP) at doses close to the acceptable daily intake as allocated by JECFA were demonstrated in immature Sprague-Dawley rats by intragastric administration, and up-regulations of estrogen-responsive biomarker genes were found in uteri of the rats by quantitative real-time RT-PCR (Q-RT-PCR). At the same time, the urinary concentrations of MP and EP, as measured by gas chromatography-mass spectrometry (GC-MS) in rats that received the same doses of MP and EP, were found to be near the high urinary levels reported in human populations in recent years. These results show the in vivo estrogenicity of MP and EP at human exposure levels, and indicate that populations exposed to large amounts of MP and EP may have a high burden of estrogenicity-related diseases. In addition, a molecular docking simulation showed interaction between the parabens and the agonist-binding pocket of human estrogen receptor α (hERα). PMID:27121550

  5. Development and Validation of a Stability-Indicating LC-Method for the Simultaneous Estimation of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and Levodropropizine Impurities.

    PubMed

    Kumar, Palakurthi Ashok; Raju, Thummala Veera Raghava; Thirupathi, Dongala; Kumar, Ravindra; Shree, Jaya

    2013-03-01

    A simple, fast, and efficient RP-HPLC method has been developed and validated for the simultaneous estimation of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and the quantification of Levodropropizine impurities in the Reswas syrup dosage form. A gradient elution method was used for the separation of all the actives and Levodropropizine impurities by using the X-Bridge C18, 150 mm × 4.6 mm, 3.5 μm column with a flow rate of 1.0 mL/min and detector wavelength at 223 nm. The mobile phase consisted of a potassium dihydrogen orthophosphate buffer and acetonitrile. All the peaks were symmetrical and well-resolved (resolution was greater than 2.5 for any pair of components) with a shorter run time. The limit of detection for Levodropropizine and its Impurity B was 0.07 μg/ml & 0.05 μg/ml, whereas the limit of quantification was 0.19 μg/ml & 0.15 μg/ml respectively. The method was validated in terms of precision, accuracy, linearity, robustness, and specificity. Degradation products resulting from the stress studies were well-resolved and did not interfere with the detection of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and Levodropropizine Impurity B, thus the test method is stability-indicating. Validation of the method was carried out as per International Conference on Harmonization (ICH) guidelines. PMID:23641334

  6. Development and Validation of a Novel Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Halometasone, Fusidic Acid, Methylparaben, and Propylparaben in Topical Pharmaceutical Formulation.

    PubMed

    Goswami, Nishant; Gupta, V Rama Mohan; Jogia, Hitesh A

    2013-06-01

    A stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the simultaneous determination of halometasone, fusidic acid, methylparaben, and propylparaben in topical pharmaceutical formulation. The desired chromatographic separation was achieved on an Agilent Zorbax CN (Cyano), 5 μm (250 × 4.6 mm) column using gradient elution at 240 nm detector wavelength. The optimized mobile phase consisted of a mixture of 0.01 M phosphate buffer and 0.1% orthophosphoric acid, pH-adjusted to 2.5 with an ammonia solution as solvent-A and acetonitrile as solvent-B. The developed method separated halometasone, fusidic acid, methylparaben, and propylparaben in the presence of known impurities/degradation products. The stability-indicating capability was established by forced degradation experiments and separation of known and unknown degradation products. The developed RP-HPLC method was validated according to the International Conference on Harmonization (ICH) guidelines. This validated method was applied for the simultaneous estimation of HM, FA, MP, and PP in commercially available cream samples. Further, the method can be extended for the estimation of HM, FA, MP, and PP in various commercially available dosage forms. PMID:23833716

  7. Development and Validation of a Stability-Indicating LC-Method for the Simultaneous Estimation of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and Levodropropizine Impurities

    PubMed Central

    Kumar, Palakurthi Ashok; Raju, Thummala Veera Raghava; Thirupathi, Dongala; Kumar, Ravindra; Shree, Jaya

    2013-01-01

    A simple, fast, and efficient RP-HPLC method has been developed and validated for the simultaneous estimation of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and the quantification of Levodropropizine impurities in the Reswas syrup dosage form. A gradient elution method was used for the separation of all the actives and Levodropropizine impurities by using the X-Bridge C18, 150 mm × 4.6 mm, 3.5 μm column with a flow rate of 1.0 mL/min and detector wavelength at 223 nm. The mobile phase consisted of a potassium dihydrogen orthophosphate buffer and acetonitrile. All the peaks were symmetrical and well-resolved (resolution was greater than 2.5 for any pair of components) with a shorter run time. The limit of detection for Levodropropizine and its Impurity B was 0.07 μg/ml & 0.05 μg/ml, whereas the limit of quantification was 0.19 μg/ml & 0.15 μg/ml respectively. The method was validated in terms of precision, accuracy, linearity, robustness, and specificity. Degradation products resulting from the stress studies were well-resolved and did not interfere with the detection of Levodropropizine, Chloropheniramine, Methylparaben, Propylparaben, and Levodropropizine Impurity B, thus the test method is stability-indicating. Validation of the method was carried out as per International Conference on Harmonization (ICH) guidelines. PMID:23641334

  8. Validated Stability-indicating Reverse-phase Ultra-performance Liquid Chromatography Method for Simultaneous Determination of Sodium Methylparaben, Sodium Propylparaben and Ketorolac Tromethamine in Topical Dosage Forms

    PubMed Central

    Roy, C.; Chakrabarty, J.; Modi, P. B.

    2013-01-01

    A sensitive, fast, and stability-indicating isocratic reverse-phase ultra-performance liquid chromatography method was developed and validated for quantitative simultaneous determination of sodium methylparaben, sodium propylparaben and ketorolac tromethamine in topical dosage forms. Separation of all peaks was achieved by using acquity ethylene bridged hybrid C18 (50×2.1 mm, 1.7 μ) as stationary phase, mobile phase used was triethylamine buffer (pH 2.5):tetrahydrofuran:methanol (665:35:300, v/v/v) with isocratic mode at a flow rate of 0.40 ml/min. All component were detected at 252 nm with 10 min run time. The described method was found to be linear in the concentration range of 248-744 μg/ml for ketorolac tromethamine, 20.8-62.4 μg/ml for sodium methylparaben and 2.38-7.13 μg/ml for sodium propylparaben with correlation coefficients more than 0.999. Method was validated in terms of specificity, linearity, accuracy, precision, solution stability, filter equivalency, and robustness as per International Conference on Harmonization guideline. Formulation was exposed to the stress conditions of peroxide, acid, base, thermal, and photolytic degradation and proven all components were well separated in the presence of degradants. PMID:24019569

  9. Development and Validation of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Phenoxyethanol, Methylparaben, Propylparaben, Mometasone Furoate, and Tazarotene in Topical Pharmaceutical Dosage Formulation

    PubMed Central

    Roy, Chinmoy; Chakrabarty, Jitamanyu

    2013-01-01

    A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of phenoxyethanol (PE), methylparaben (MP), propylparaben (PP), mometasone furoate (MF), and tazarotene (TA) in topical pharmaceutical dosage formulation. The desired chromatographic separation was achieved on the Waters X-Bridge™ C18 (50×4.6mm, 3.5μ) column using gradient elution at 256 nm detection wavelength. The optimized mobile phase consisted of 0.1%v/v orthophosphoric acid in water as solvent-A and acetonitrile as solvent-B. The method showed linearity over the range of 5.88–61.76 μg/mL, 0.18–62.36 μg/mL, 0.17–6.26 μg/mL, 0.47–31.22 μg/mL, and 0.44–30.45 μg/mL for PE, MP, PP, MF, and TA, respectively. The recovery for all of the components was in the range of 98–102%. The stability-indicating capability of the developed method was established by analysing the forced degradation samples, in which the spectral purity of PE, MP, PP, MF, and TA along with the separation of degradation products from the analyte peaks was achieved. The proposed method was successfully applied for the quantitative determination of PE, MP, PP, MF, and TA in a cream sample. PMID:24482766

  10. Development and Validation of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Phenoxyethanol, Methylparaben, Propylparaben, Mometasone Furoate, and Tazarotene in Topical Pharmaceutical Dosage Formulation.

    PubMed

    Roy, Chinmoy; Chakrabarty, Jitamanyu

    2013-12-01

    A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of phenoxyethanol (PE), methylparaben (MP), propylparaben (PP), mometasone furoate (MF), and tazarotene (TA) in topical pharmaceutical dosage formulation. The desired chromatographic separation was achieved on the Waters X-Bridge™ C18 (50×4.6mm, 3.5μ) column using gradient elution at 256 nm detection wavelength. The optimized mobile phase consisted of 0.1%v/v orthophosphoric acid in water as solvent-A and acetonitrile as solvent-B. The method showed linearity over the range of 5.88-61.76 μg/mL, 0.18-62.36 μg/mL, 0.17-6.26 μg/mL, 0.47-31.22 μg/mL, and 0.44-30.45 μg/mL for PE, MP, PP, MF, and TA, respectively. The recovery for all of the components was in the range of 98-102%. The stability-indicating capability of the developed method was established by analysing the forced degradation samples, in which the spectral purity of PE, MP, PP, MF, and TA along with the separation of degradation products from the analyte peaks was achieved. The proposed method was successfully applied for the quantitative determination of PE, MP, PP, MF, and TA in a cream sample. PMID:24482766

  11. Quality by Design-Based Development of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Methylparaben, Propylparaben, Diethylamino Hydroxybenzoyl Hexyl Benzoate, and Octinoxate in Topical Pharmaceutical Formulation.

    PubMed

    Roy, Chinmoy; Chakrabarty, Jitamanyu

    2014-09-01

    A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of methylparaben (MP), propylparaben (PP), diethylamino hydroxybenzoyl hexyl benzoate (DAHHB), and octinoxate (OCT) in topical pharmaceutical formulation. The desired chromatographic separation was achieved on the Kinetex(TM) C18 (250 × 4.6 mm, 5 μm) column using gradient elution at 257 nm detection wavelength. The optimized mobile phase consisted of a buffer : acetonitrile : tetrahydrofuran (60 : 30 : 10, v/v/v) as solvent A and acetonitrile : tetrahydrofuran (70 : 30, v/v) as solvent B. The method showed linearity over the range of 0.19-148.4 μg/mL, 0.23-15.3 μg/mL, 1.97-600.5 μg/mL, and 1.85-451.5 μg/mL for MP, PP, DAHHB, and OCT, respectively. Recovery for all the components was found to be in the range of 98-102%. The stability-indicating capability of the developed method was established by analysing the forced degradation samples in which the spectral purity of MP, PP, DAHHB, and OCT, along with the separation of the degradation products from the analyte peaks, was achieved. The proposed method was successfully applied for the quantitative determination of MP, PP, DAHHB, and OCT in the lotion sample. The design expert with ANOVA software with the linear model was applied and a 2(4) full factorial design was employed to estimate the model coefficients and also to check the robustness of the method. Results of the two-level full factorial design, 2(4) with 20 runs including four centrepoint analysis based on the variance analysis (ANOVA), demonstrated that all four factors, as well as the interactions of resolution between DAHHB and OCT are statistically significant. PMID:25853065

  12. 21 CFR 556.550 - Propylparaben.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Propylparaben. 556.550 Section 556.550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs §...

  13. 21 CFR 556.390 - Methylparaben.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methylparaben. 556.390 Section 556.390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs §...

  14. Degradation of ethylparaben under simulated sunlight using photo-Fenton.

    PubMed

    Zúñiga-Benítez, Henry; Peñuela, Gustavo A

    2016-01-01

    Ethylparaben (EPB) has been classified by different research groups as a potential endocrine-disrupting chemical, implying that it can potentially interfere with the normal balance of the endocrine system of living beings, which with its presence in different effluents, including drinking water, generates the need to seek methods that allow its removal from different water bodies. Advanced oxidation processes have been employed widely to remove organic compounds from different matrices. In this way, Fenton technology (process based on the reaction between ferrous ions and hydrogen peroxide) has been able to degrade different substrates, but due to the Fe(2+) requirements to carry out the reaction optimally, combination of the conventional Fenton process with visible light radiation (photo-Fenton) is an alternative used in the treatment of pollution due to the presence of chemicals. In this way, the effectiveness of photo-Fenton on EPB degradation was assessed using a face-centered central composite experimental design that allowed assessment of the effects of Fe(2+) and H2O2 initial concentrations on process. In general, results indicated that after 180 min of reaction almost all EPB was eliminated, the dissolved organic carbon in solution was reduced and the sample biodegradability index was increased. PMID:26901724

  15. Nanomolar detection of methylparaben by a cost-effective hemoglobin-based biosensor.

    PubMed

    Hajian, A; Ghodsi, J; Afraz, A; Yurchenko, O; Urban, G

    2016-12-01

    This work describes the development of a new biosensor for methylparaben determination using electrocatalytic properties of hemoglobin in the presence of hydrogen peroxide. The voltammetric oxidation of methylparaben by the proposed biosensor in phosphate buffer (pH=7.0), a physiological pH, was studied and it was confirmed that methylparaben undergoes a one electron-one proton reaction in a diffusion-controlled process. The biosensor was fabricated by carbon paste electrode modified with hemoglobin and multiwalled carbon nanotube. Based on the excellent electrochemical properties of the modified electrode, a sensitive voltammetric method was used for determination of methylparaben within a linear range from 0.1 to 13μmolL(-1) and detection limit of 25nmolL(-1). The developed biosensor possessed accurate and rapid response to methylparaben and showed good sensitivity, stability, and repeatability. Finally, the applicability of the proposed biosensor was verified by methylparaben evaluation in various real samples. PMID:27612696

  16. Stability of methyl p-hydroxybenzoate (methylparaben) to gamma radiolysis

    NASA Astrophysics Data System (ADS)

    Angelini, Giancarlo; Bucci, Roberto; Colosimo, Marcello; Margonelli, Andrea

    1998-01-01

    The stability of methyl p-hydroxybenzoate during 60Co γ-radiolysis was studied in the solid state and in 10 μM water solution. The work was undertaken as a model to be extended to radiolytic sterilization of pharmaceutical preparations. Only in water moderate decomposition was observed at high doses (50 KGy, whilst at 5 kGy sterilization was verified. Methylparaben labelled with carbon-14 on the carboxyl group provided the decomposition yield by the reverse isotope dilution method; mass balances were drawn and mechanisms suggested.

  17. Comparison of antimicrobial activity of essential oils, plant extracts and methylparaben in cosmetic emulsions: 2 months study.

    PubMed

    Herman, Anna

    2014-09-01

    The aim of the study was to compare the preservative effectiveness of plant extracts (Matricaria chamomilla, Aloe vera, Calendula officinalis) and essential oils (Lavandulla officinalis, Melaleuca alternifolia, Cinnamomum zeylanicum) with methylparaben in cosmetic emulsions against skin microflora during 2 months of application by volunteers. Cosmetic emulsions with extracts (2.5 %), essential oils (2.5 %), methylparaben (0.4 %) or placebo were tested by 40 volunteers during 2 months of treatment. In order to determine microbial purity of the emulsions, the samples were taken after 0, 2, 4, 6 and 8 weeks of application. Throughout the trial period it was revealed that only cinnamon oil completely inhibited the growth of bacteria, yeast and mould, as compared to all other essential oils, plant extracts and methylparaben in the tested emulsions. This result shows that cinnamon oil could successfully replace the use of methylparaben in cosmetics, at the same time ensuring microbiological purity of a cosmetic product under its in-use and storage conditions. PMID:24891745

  18. Influence of fat addition on the antimicrobial activity of sodium lactate, lauric arginate and methylparaben in minced meat.

    PubMed

    Magrinyà, Núria; Terjung, Nino; Loeffler, Myriam; Gibis, Monika; Bou, Ricard; Weiss, Jochen

    2015-12-23

    A minced meat model system containing three different fat levels (0, 15, and 50 wt.%) was used to evaluate the antimicrobial efficacy of three antimicrobials with different aqueous solubilities (sodium lactate>lauric arginate (Nα-lauroyl-L-arginine ethyl ester, LAE)>methylparaben). Various concentrations of sodium lactate (20, 40, and 60 mg/g), lauric arginate (0.5, 1, 1.5, 2.0, and 2.5 mg/g) and methylparaben (0.1, 0.5, 1.0, and 2.0 mg/g) were used to evaluate the antimicrobial activity against natural meat microbiota (total aerobic mesophilic colony counts, coliform bacteria, and lactic acid bacteria). The results indicate that the three antimicrobials tested are influenced at different strengths by the changes of the fat addition of the minced meat. The antimicrobial efficacy of LAE and methylparaben is increased by a higher fat content in the meat batter, whereas for lactate no clear lactate proportionality relationship can be seen. This structure sensitivity is most strongly pronounced with lauric arginate, which we attributed to the amphiphilic character of the molecule. PMID:26344644

  19. Bioanalysis of propylparaben and p-hydroxybenzoic acid, and their sulfate conjugates in rat plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhao, Yue; Liu, Guowen; Shen, Hongwu; Shen, Jim X; Aubry, Anne-Françoise; Sivaraman, Lakshmi; Arnold, Mark E

    2014-02-01

    Two rugged liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the determination of propylparaben, its major metabolite, p-hydroxybenzoic acid (pHBA), and their sulfate conjugates have been developed and validated in citric acid-treated rat plasma. To prevent propylparaben being hydrolyzed to pHBA ex vivo, rat plasma was first treated with citric acid; then collected and processed at a reduced temperature (ice bath). Stable isotope labeled internal standards, d4-propylparaben, (13)C6-pHBA, and the d4-labeled internal standards of their sulfate conjugates were used in the methods. The analytes were extracted from the matrix using protein precipitation, followed by chromatographic separation on a Waters ACQUITY UPLC HSS T3 column. Quantification using negative ion electrospray was performed on a Sciex API 4000 mass spectrometer. The analytical ranges were established from 2.00 to 200 ng/mL for propylparaben, 50.0-5000 ng/mL for pHBA, 50.0-10,000 ng/mL for the sulfate conjugate of propylparaben (SPP) and 200-40,000 ng/mL for the sulfate conjugate of pHBA (SHBA). Inter- and intra-run precision for the quality control samples were less than 5.3% and 4.4% for all analytes; and the overall accuracy was within ±5.7% of the nominal values. The validated bioanalytical methods demonstrated excellent sensitivity, specificity, accuracy and precision and were successfully applied to a rat toxicology study under the regulations of Good Laboratory Practices (GLP). Strategies have been developed and applied toward overcoming the challenges related to analyte stability, and environmental and endogenous background. PMID:24412689

  20. IUPAC-NIST Solubility Data Series. 90. Hydroxybenzoic Acid Derivatives in Binary and Ternary Systems. Part II. Hydroxybenzoic Acids, Hydroxybenzoates, and Hydroxybenzoic Acid Salts in Nonaqueous Systems

    NASA Astrophysics Data System (ADS)

    Goto, Ayako; Miyamoto, Hiroshi; Salomon, Mark; Goto, Rensuke; Fukuda, Hiroshi; Königsberger, Erich; Königsberger, Lan-Chi; Scharlin, Pirketta

    2011-06-01

    The solid-liquid solubility data for well defined nonaqueous binary and ternary systems are reviewed. One component includes hydroxybenzoic acid, hydroxybenzoate, and hydroxybenzoic acid salt, and another component includes a variety of organic compounds (hydrocarbons, alcohols, halogenated hydrocarbons, carboxylic acids, esters, et al.) and carbon dioxide. The ternary systems include mixtures of organic substances of various classes and carbon dioxide. The total number of compilation sheets is 270 for six types of system. Almost all data are expressed as mass percent and mole fraction as well as the originally reported units, while some data are expressed as molar concentration. Critical evaluation was carried out for the binary nonaqueous systems of 2-, 3-, and 4-hydroxybenzoic acids and hydroxybenzoates (methylparaben, ethylparaben, propylparaben, and butylparaben) in alcohols, 1-heptane, and benzene.

  1. Degradation of methylparaben in water by corona plasma coupled with ozonation.

    PubMed

    Dobrin, D; Magureanu, M; Bradu, C; Mandache, N B; Ionita, P; Parvulescu, V I

    2014-11-01

    The degradation of methylparaben (MeP) in water was investigated using a pulsed corona discharge generated in oxygen, above the liquid. A comparison was made between results obtained in semi-batch corona (SBC) configuration (stationary solution, continuous gas flow) and results obtained in a semi-batch corona with recirculation combined with ozonation (SBCR + O3), where the liquid is continuously circulated between a solution reservoir and the plasma reactor and the effluent gas containing ozone is bubbled through the solution in the reservoir. It was found that MeP was completely degraded after 10-15 min of treatment in both configurations. Oxidation by ozone alone, in the absence of plasma, was a slower process. The energy efficiency for MeP removal (Y MeP) and for mineralization (Y TOC) was significantly higher in the SBCR + O3 configuration (Y MeP = 7.1 g/kWh at 90 % MeP removal and Y TOC = 0.41 g/kWh at 50 % total organic carbon (TOC) removal) than in the SBC configuration (Y MeP = 0.6 g/kWh at 90 % MeP removal and Y TOC = 0.11 g/kWh at 50 % TOC removal). PMID:24801291

  2. Influence of inorganic ions and selected emerging contaminants on the degradation of Methylparaben: A sonochemical approach.

    PubMed

    Sasi, Subha; Rayaroth, Manoj P; Devadasan, Dineep; Aravind, Usha K; Aravindakumar, Charuvila T

    2015-12-30

    The study on the possible pathway of hydroxyl radicals mediated sonolytic degradation of paraben in water is reported. Methylparaben (MPB) which is the most utilized of paraben family is selected as a model emerging pollutant. The influence of common anions and some selected emerging contaminants that may coexist in typical water matrix on the degradation pattern is analyzed alongside. Among the anions, carbonate presents a negative influence which is attributed to the competition for OH radical. Some emerging contaminants also showed negative impact on degradation as was clear from HPLC data. The intermediates, analyzed by LC-Q-TOF-MS include hydroxylated and hydrolytic products. Three major steps (aromatic hydroxylation, hydroxylation at the ester chain and hydrolysis) are proposed to involve in the reaction of OH radical with MPB which ultimately leads to mineralization. The intensity of formation and decay of mono and dihydroxy products of MPB in the presence of additives have also been evaluated. COD analysis indicates a percentage reduction of 98% at 90 min of sonolysis and further increase in the degradation time resulted complete mineralization, which became evident from the mass spectrometric data. MTT assay revealed considerable decrease in the potential cytotoxicity. PMID:26184803

  3. Determination of ambroxol hydrochloride, methylparaben and benzoic acid in pharmaceutical preparations based on sequential injection technique coupled with monolithic column.

    PubMed

    Satínský, Dalibor; Huclová, Jitka; Ferreira, Raquel L C; Montenegro, Maria Conceição B S M; Solich, Petr

    2006-02-13

    The porous monolithic columns show high performance at relatively low pressure. The coupling of short monoliths with sequential injection technique (SIA) results in a new approach to implementation of separation step to non-separation low-pressure method. In this contribution, a new separation method for simultaneous determination of ambroxol, methylparaben and benzoic acid was developed based on a novel reversed-phase sequential injection chromatography (SIC) technique with UV detection. A Chromolith SpeedROD RP-18e, 50-4.6 mm column with 10 mm precolumn and a FIAlab 3000 system with a six-port selection valve and 5 ml syringe were used for sequential injection chromatographic separations in our study. The mobile phase used was acetonitrile-tetrahydrofuran-0.05M acetic acid (10:10:90, v/v/v), pH 3.75 adjusted with triethylamine, flow rate 0.48 mlmin(-1), UV-detection was at 245 nm. The analysis time was <11 min. A new SIC method was validated and compared with HPLC. The method was found to be useful for the routine analysis of the active compounds ambroxol and preservatives (methylparaben or benzoic acid) in various pharmaceutical syrups and drops. PMID:16165338

  4. Ultra-high-performance liquid chromatography-tandem mass spectrometry for determining the presence of eleven personal care products in surface and wastewaters.

    PubMed

    Pedrouzo, Marta; Borrull, Francesc; Marcé, Rosa Maria; Pocurull, Eva

    2009-10-16

    Personal care products (PCPs) are widely used emerging contaminants which can cause adverse environmental effects. This paper reports the development and validation of a method based on solid-phase extraction (SPE) and ultra-high-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (UHPLC-(ESI)MS-MS) for simultaneously determining eleven PCPs: 4 preservatives (methylparaben; ethylparaben; benzylparaben; propylparaben); 2 antimicrobial agents (triclocarban and triclosan) and 5 UV filters (2,4-dihydroxybenzophenone; 2,2-dihydroxy-4-methoxybenzophenone; benzophenone-3; octocrylene and octyldimethyl-p-aminobenzoic acid) in environmental waters in only 9 run minutes of chromatographic separation. The SPE was carried out with two polymeric cartridges (Oasis HLB and Bond Elut Plexa). The recoveries obtained with Bond Elut Plexa were between 69% and 101% for 500 mL of river waters, with the exception of octyldimethyl-p-aminobenzoic acid (46%). Limits of detection for 500 mL of river water were in the range of 1-5 ng/L. Oasis HLB was chosen for wastewater samples with recoveries between 38% and 92% (250 mL of effluents) and 36-89% (100mL of influents). In both wastewater samples, octyldimethyl-p-aminobenzoic acid and methylparaben showed the lowest recoveries (20% and 27%). The method revealed benzophenone-3 as having the highest concentration levels ( 7 ng/L) in river waters. Most of PCPs determined were found in influent waters being methylparaben and propylparaben the ones found at highest concentration with values of 5613 and 1945 ng/L, respectively. In effluent waters, significant lower levels of some PCPs were found, being benzophenone-3 the one found at the highest concentration (100 ng/L). PMID:19747689

  5. Structural Changes in PEO-PPO-PEO Gels Induced by Methylparaben and Dexamethasone Observed Using Time-Resolved SAXS

    SciTech Connect

    Meznarich, Norman A.K.; Juggernauth, K Anne; Batzli, Kiersten M; Love, Brian J

    2011-11-17

    Aqueous solutions of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) triblock copolymers (commercially available as Pluronic surfactants) micellize and structurally arrange into cubic quasicrystalline lattices as their temperature is raised. This structural evolution is seen macroscopically as a gelation, and the presence of these ordered phases can be controlled through both polymer concentration and temperature. The presence of added solutes within the dispersions can also affect the onset and kinetics of structure formation. Here we investigate the structures formed in Pluronic F127 solutions ranging from 20 to 30% with two pharmaceutical additives [methylparaben (MP) and dexamethasone (DX)] using small-angle X-ray scattering (SAXS). We observe both the progressive evolution and breakdown of these structures as the temperature is increased from 0 to 80 °C. Additionally, we conducted time-resolved SAXS measurements to elucidate the kinetics of the structural evolution. On the basis of the evolution of scattering peaks as the samples were being heated, we suggest that added MP changes the nucleation behavior of fcc phases within the sample from a heterogeneous process to a more homogeneous distribution of nucleated species. MP and DX also stabilize the micelle lattices, allowing them to persevere at higher temperatures. We observed the unusual result that the presence of DX caused the primary peaks of the structure factor to be suppressed, while preserving the higher order peaks. The primary peaks reappeared at the highest temperatures tested.

  6. Preparation of a magnetic molecularly imprinted polymer by atom-transfer radical polymerization for the extraction of parabens from fruit juices.

    PubMed

    You, Xiaoxiao; Piao, Chungying; Chen, Ligang

    2016-07-01

    A silica-based surface magnetic molecularly imprinted polymer for the selective recognition of parabens was prepared using a facile and general method that combined atom-transfer radical polymerization with surface imprinting technique. The prepared magnetic molecularly imprinted polymer was characterized by transmission electron microscopy, Fourier transform infrared spectrometry and physical property measurement. The isothermal adsorption experiment and kinetics adsorption experiment investigated the adsorption property of magnetic molecularly imprinted polymer to template molecule. The four parabens including methylparaben, ethylparaben, propylparaben, and butylparaben were used to assess the rebinding selectivity. An extraction method, which used magnetic molecularly imprinted polymer as adsorbents coupled with high-performance liquid chromatography for the determination of the four parabens in fruit juice samples was developed. Under the optimal conditions, the limits of detections of the four parabens were 0.028, 0.026, 0.021, and 0.026 mg/L, respectively. The precision expressed as relative standard deviation ranging from 2.6 to 8.9% was obtained. In all three fortified levels, recoveries of parabens were in the range of 72.5-89.4%. The proposed method has been applied to different fruit juice samples including orange juice, grape juice, apple juice and peach juice, and satisfactory results were obtained. PMID:27214157

  7. Parabens determination in cosmetic and personal care products exploiting a multi-syringe chromatographic (MSC) system and chemiluminescent detection.

    PubMed

    Rodas, Melisa; Portugal, Lindomar A; Avivar, Jessica; Estela, José Manuel; Cerdà, Víctor

    2015-10-01

    Parabens are widely used in dairy products, such as in cosmetics and personal care products. Thus, in this work a multi-syringe chromatographic (MSC) system is proposed for the first time for the determination of four parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) in cosmetics and personal care products, as a simpler, practical, and low cost alternative to HPLC methods. Separation was achieved using a 5mm-long precolumn of reversed phase C18 and multi-isocratic separation, i.e. using two consecutive mobile phases, 12:88 acetonitrile:water and 28:72 acetonitrile:water. The use of a multi-syringe buret allowed the easy implementation of chemiluminescent (CL) detection after separation. The chemiluminescent detection is based on the reduction of Ce(IV) by p-hydroxybenzoic acid, product of the acid hydrolysis of parabens, to excite rhodamine 6G (Rho 6G) and measure the resulting light emission. Multivariate designs combined with the concepts of multiple response treatments and desirability functions have been employed to simultaneously optimize and evaluate the responses. The optimized method has proved to be sensitive and precise, obtaining limits of detection between 20 and 40 µg L(-1) and RSD <4.9% in all cases. The method was satisfactorily applied to cosmetics and personal care products, obtaining no significant differences at a confidence level of 95% comparing with the HPLC reference method. PMID:26078157

  8. Theoretical investigation on the kinetics and mechanisms of hydroxyl radical-induced transformation of parabens and its consequences for toxicity: Influence of alkyl-chain length.

    PubMed

    Gao, Yanpeng; Ji, Yuemeng; Li, Guiying; An, Taicheng

    2016-03-15

    As emerging organic contaminants (EOCs), the ubiquitous presence of preservative parabens in water causes a serious environmental concern. Hydroxyl radical ((•)OH) is a strong oxidant that can degrade EOCs through photochemistry in surface water environments as well as in advanced oxidation processes (AOPs). To better understand the degradation mechanisms, kinetics, and products toxicity of the preservative parabens in aquatic environments and AOPs, the (•)OH-initiated degradation reactions of the four parabens were investigated systematically using a computational approach. The four studied parabens with increase of alkyl-chain length were methylparaben (MPB), ethylparaben (EPB), propylparaben (PPB), and dibutylparaben (BPB). Results showed that the four parabens can be initially attacked by (•)OH through (•)OH-addition and H-abstraction routes. The (•)OH-addition route was more important for the degradation of shorter alkyl-chain parabens like MPB and EPB, while the H-abstraction route was predominant for the degradation of parabens with longer alkyl-chain for example PPB and BPB. In assessing the aquatic toxicity of parabens and their degradation products using the model calculations, the products of the (•)OH-addition route were found to be more toxic to green algae than original parabens. Although all degradation products were less toxic to daphnia and fish than corresponding parental parabens, they could be still harmful to these aquatic organisms. Furthermore, as alkyl-chain length increased, the ecotoxicity of parabens and their degradation products was found to be also increased. PMID:26773489

  9. Direct rapid analysis of multiple PPCPs in municipal wastewater using ultrahigh performance liquid chromatography-tandem mass spectrometry without SPE pre-concentration.

    PubMed

    Yu, Ke; Li, Bing; Zhang, Tong

    2012-08-13

    Ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was utilized to develop a rapid, sensitive and reliable method without solid phase extraction (SPE) pre-concentration for trace analysis of 11 pharmaceuticals and personal care products (PPCPs) in influent and effluent from municipal wastewater treatment plants (WWTPs). This method not only shortened the analysis time but also reduced analysis cost significantly by omitting SPE process and avoiding the consumption of SPE cartridge. Detection parameters for UHPLC-MS/MS analysis were optimized, including sample pH, eluent, mobile phase (solvent and additive), column temperature, and flow rate. Under the optimal conditions, all analytes were well separated and detected within 8.0min by UHPLC-MS/MS. The method quantification limits (MQLs) for the 11 PPCPs ranged from 0.040 to 88ngL(-1) and from 0.030 to 90ngL(-1) for influent and effluent, respectively. The matrix effect was systematically investigated and quantified for different types of samples. The analysis of influent and effluent samples of two WWTPs in Hong Kong revealed the presence of 11 PPCPs, including acyclovir, benzophenone-3, benzylparaben, carbamazepine, ethylparaben, fluconazole, fluoxetine, methylparaben, metronidazole, propylparaben, and ranitidine. Their concentrations ranged from 9.1 to 1810ngL(-1) in influent and from 6.5 to 823ngL(-1) in effluent samples collected from Hong Kong WWTPs. PMID:22790701

  10. Rapid determination of parabens in seafood sauces by high-performance liquid chromatography: A practical comparison of core-shell particles and sub-2 μm fully porous particles.

    PubMed

    Ye, Jing; Cao, Xiaoji; Cheng, Zhuo; Qin, Ye; Lu, Yanbin

    2015-12-01

    In this work, the chromatographic performance of superficially porous particles (Halo core-shell C18 column, 50 mm × 2.1 mm, 2.7 μm) was compared with that of sub-2 μm fully porous particles (Acquity BEH C18 , 50 mm × 2.1 mm, 1.7 μm). Four parabens, methylparaben, ethylparaben, propylparaben, and butylparaben, were used as representative compounds for calculating the plate heights in a wide flow rate range and analyzed on the basis of the Van Deemter and Knox equations. Theoretical Poppe plots were constructed for each column to compare their kinetic performance. Both phases gave similar minimum plate heights when using nonreduced coordinates. Meanwhile, the flat C-term of the core-shell column provided the possibilities for applying high flow rates without significant loss in efficiency. The low backpressure of core-shell particles allowed this kind of column, especially compatible with conventional high-performance liquid chromatography systems. Based on these factors, a simple high-performance liquid chromatography method was established and validated for the determination of parabens in various seafood sauces using the Halo core-shell C18 column for separation. PMID:26383987

  11. Ozonation of parabens in aqueous solution: kinetics and mechanism of degradation.

    PubMed

    Tay, Kheng Soo; Rahman, Noorsaadah Abd; Abas, Mhd Radzi Bin

    2010-12-01

    This study investigated the reaction kinetics and degradation mechanism of parabens (methylparaben, ethylparaben, propylparaben and butylparaben) during ozonation. Experiments were performed at pH 2, 6 and 12 to determine the rate constants for the reaction of protonated, undissociated and dissociated paraben with ozone. The rate constants for the reaction of ozone with dissociated parabens (3.3 × 10(9)-4.2 × 10(9)M(-1)s(-1)) were found to be 10(4) times higher than the undissociated parabens (2.5 × 10(5)-4.4 × 10(5)M(-1)s(-1)) and 10(7) times higher than with the protonated parabens (1.02 × 10(2)-1.38 × 10(2)M(-1)s(-1)). The second-order rate constants for the reaction between parabens with hydroxyl radicals were found to vary from 6.8 × 10(9) to 9.2 × 10(9)M(-1)s(-1). Characterization of degradation by-products (DBPs) formed during the ozonation of each selected parabens has been carried out using GCMS after silylation. Twenty DBPs formed during ozonation of selected parabens have been identified. Hydroxylation has been found to be the major reaction for the formation of the identified DBPs. Through the hydroxylation reaction, a variety of hydroxylated parabens was formed. PMID:20875662

  12. Simultaneous determination of antioxidants, preservatives and sweetener additives in food and cosmetics by flow injection analysis coupled to a monolithic column.

    PubMed

    García-Jiménez, J F; Valencia, M C; Capitán-Vallvey, L F

    2007-07-01

    Today it is common to find samples with various additives from several families. This is the case of sweeteners, preservatives and antioxidants. We have selected a set of additives broadly used in foods and cosmetics with an ample variety of polarities, namely: aspartame (AS), acesulfame (AK)/saccharin (SA), methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), propylgallate (PG) and butylhydroxyanisole (BA). The monolithic column used as separative system is a 5 mm commercial precolumn of silica C18 coupled to a flow injection manifold working with a peristaltic pump. The mixture was separated in only 400 s with resolution factors greater than 1.1 in all cases. To achieve the separation in the FIA system we used two carriers: first, a mixture of ACN/water buffered with 10 mM pH 6.0 phosphate buffer and second, a methanol:water mixture to improve the carrier strength and speed up the more apolar analytes at 3.5 mL min(-1). Detection is accomplished by means of a diode array spectrometer at the respective wavelength of each compound. The comparison of the analytical parameters obtained for this procedure with a standard HPLC method validates our new method, obtaining a method that is quick, with high repeatability and reproducibility and with good resolution between analytes. We have successfully applied the method to real food and cosmetics samples. PMID:17586119

  13. Determination of personal care products and hormones in leachate and groundwater from Polish MSW landfills by ultrasound-assisted emulsification microextraction and GC-MS.

    PubMed

    Kapelewska, Justyna; Kotowska, Urszula; Wiśniewska, Katarzyna

    2016-01-01

    Determination of the endocrine disrupting compounds (EDCs) in leachate and groundwater samples from the landfill sites is very important because of the proven harmful effects of these compounds on human and animal organisms. A method combining ultrasound-assisted emulsification microextraction (USAEME) and gas chromatography-mass spectrometry (GC-MS) was developed for simultaneous determination of seven personal care products (PCPs): methylparaben (MP), ethylparaben (EP), propylparaben (PP), buthylparaben (BP), benzophenone (BPh), 3-(4-methylbenzylidene)camphor (4-MBC), N,N-diethyltoluamide (DEET), and two hormones: estrone (E1) and β-estradiol (E2) in landfill leachate and groundwater samples. The limit of detection (LOD)/limit of quantification (LOQ) values in landfill leachate and groundwater samples were in the range of 0.003-0.083/0.009-0.277 μg L(-1) and 0.001-0.015/0.002-0.049 μg L(-1), respectively. Quantitative recoveries and satisfactory precision were obtained. All studied compounds were found in the landfill leachates from Polish municipal solid waste (MSW) landfills; the concentrations were between 0.66 and 202.42 μg L(-1). The concentration of pollutants in groundwater samples was generally below 0.1 μg L(-1). PMID:26381788

  14. Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum.

    PubMed

    Barr, L; Metaxas, G; Harbach, C A J; Savoy, L A; Darbre, P D

    2012-03-01

    The concentrations of five esters of p-hydroxybenzoic acid (parabens) were measured using HPLC-MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n-propylparaben [16.8 (range 0-2052.7)] and methylparaben [16.6 (range 0-5102.9)]; levels were lower for n-butylparaben [5.8 (range 0-95.4)], ethylparaben [3.4 (range 0-499.7)] and isobutylparaben 2.1 (range 0-802.9). The overall median value for total paraben was 85.5 ng g(-1) tissue (range 0-5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37-91 years), length of breast feeding (0-23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n-propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA). PMID:22237600

  15. Glucocorticoid-like activity of propylparaben, butylparaben, diethylhexyl phthalate and tetramethrin mixtures studied in the MDA-kb2 cell line.

    PubMed

    Klopčič, Ivana; Kolšek, Katra; Dolenc, Marija Sollner

    2015-01-22

    Endocrine-disrupting compounds can interfere with the endocrine organs or hormone system and cause tumors, birth defects and developmental disorders in humans. The estrogen-like activity of compounds has been widely studied but little is known concerning their possible modulation of the glucocorticoid receptor. Steroidal (synthetic and natural) and non-steroidal endocrine-active compounds commonly occur as complex mixtures in human environments. Identification of such molecular species, which are responsible for modulating the glucocorticoid receptor are necessary to fully assess their risk. We have used the MDA-kb2 cell line, which expresses endogenous glucocorticoid receptor and a stably transfected luciferase reporter gene construct, to quantify the glucocorticoid-like activity of four compounds present in products in everyday use - propylparaben (PP), butylparaben (BP), diethylhexyl phthalate (DEHP) and tetramethrin (TM). We tested all possible combinations of these compounds at two concentrations (1 μM and 10 nM) and compared their glucocorticoid-like activity. At the concentration of 1 μM seven mixtures were identified to have glucocorticoid-like activity except: DEHP+TM, BP+TM, DEHP+PP+TM, BP+PP+TM. At the concentration of 10 nM only three mixtures have glucocorticoid modulatory activity: DEHP+PP, BP+PP, DEHP+BP+PP+TM. Identified glucocorticoid-like activities were between 1.25 and 1.51 fold at the concentration of 1 μM and between 1.23 and 1.44 fold at the concentration of 10 nM in comparison with the solvent control. Individually BP, PP, and DEHP had glucocorticoid-like activity of 1.60, 1.57 and 1.50 fold over the solvent control at the concentration of 1 μM. On the other hand PP and DEHP, at the concentration of 10nM, showed no glucocorticoid-like activity, while BP showed 1.44 fold. The assertion that individual glucocorticoid-like compounds do not produce harm because they are present at low, ineffective levels in humans may be irrelevant when we

  16. Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: using a pig-ear model in vitro.

    PubMed

    Pažoureková, Silvia; Hojerová, Jarmila; Klimová, Zuzana; Lucová, Marianna

    2013-09-01

    Currently, there is a trend to reduce of parabens use due to concern about the safety of their unmetabolised forms. This paper focused on dermal absorption rate and effectiveness of first-pass biotransformation of methylparaben (MP) under in-use conditions of skincare products. 24-h exposure of previously frozen intact and tapestripped (20 strips) pig-ear skin to nine vehicles containing 0.1% MP (AD, applied dose of 10 μg/cm²), resulted in 2.0-5.8%AD and 2.9-7.6%AD of unmetabolised MP, and 37.0-73.0%AD and 56.0-95.0%AD of p-hydroxybenzoic acid, respectively, in the receptor fluid. The absorption rate of MP was higher from emulsions than from hydrogels, from enhancer-containing vehicles than from enhancer-free vehicles, and when skin was damaged. Experiments confirmed that the freezing of pig-ear skin slightly reduces hydrolysis of MP. After 4-h exposure of intact freshly excised and intact frozen stored skin, amount of

  17. Influence of relative humidity on the mechanical and drug release properties of theophylline pellets coated with an acrylic polymer containing methylparaben as a non-traditional plasticizer.

    PubMed

    Wu, C; McGinity, J W

    2000-09-01

    The purpose of this study was to investigate the influence of relative humidity (RH) on the mechanical and dissolution properties of theophylline pellets coated with Eudragit((R)) RS 30 D/RL 30 D containing methylparaben (MP) as a non-traditional plasticizer. The coated beads were stored at 23 degrees C and at different relative humidities (0, 29, 51, 75 and 84% RH). The effect of storage conditions on the rate of drug release from coated beads was determined in pH 7.4 phosphate buffer solution. The mechanical properties, including tensile strength and Young's modulus, of individual beads were determined by a diametral compression method with a Chatillon((R)) tension/compression apparatus. The morphology of the intact and fractured beads was investigated using scanning electron microscopy (SEM). The moisture content of the polymeric films was determined using a Karl Fischer coulometric moisture analyzer. The results from the mechanical studies demonstrated that an increase in the relative humidity resulted in a decrease in the tensile strength and Young's modulus of the coated beads. SEM photographs showed that coated beads stored at 0% RH exhibited brittle fracture failure. The coated beads stored at 84% RH showed ductile behavior, which was attributed to the hydroplasticization effect on the acrylic polymer due to the uptake of moisture. The moisture content in the films was also shown to influence the rate of drug release from Eudragit((R)) RS 30 D/RL 30 D coated beads containing MP as the plasticizer. The change in release profiles could be minimized when the relative humidity was reduced to zero. The dissolution rate of theophylline from the coated beads decreased when stored at high relative humidities. This trend was reversed when the coated beads that were stored at 84% RH for 5 weeks, were then equilibrated at 0% RH. PMID:10962239

  18. Determination of hormones, a plasticizer, preservatives, perfluoroalkylated compounds, and a flame retardant in water samples by ultrasound-assisted dispersive liquid-liquid microextraction based on the solidification of a floating organic drop.

    PubMed

    Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

    2015-10-01

    Dispersive liquid-liquid microextraction based on the solidification of a floating organic drop (DLLME-SFO) is a novel extraction technique commonly applied for the extraction on a specific group of compounds. In this paper, the applicability of ultrasound-assisted DLLME-SFO for multiresidue extraction has been evaluated. A method for the simultaneous extraction of four hormones (17α-ethinylestradiol, 17β-estradiol, estriol and estrone), a plasticizer (bisphenol A), three preservatives (methyl-, ethyl- and propylparaben), six perfluoroalkylated compounds (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, from C4 to C8), and a brominated flame retardant (hexabromocyclododecane) has been developed and validated for their extraction from surface water and tap water. Determination was carried out by high-performance liquid chromatography-tandem mass spectrometry in negative ionization mode. Recoveries of the target compounds were highly dependent on their log K(ow) values. Linear relationship between recoveries and log K(ow) values was observed for compounds from the same group (hormones, preservatives and perfluoroalkylated carboxylic acids). The lowest recoveries were obtained for the less hydrophobic compounds (estriol (43%), methylparaben (32%), ethylparaben (45%) and the perfluorinated compounds of shorter alkyl chain (C4: 17%, C5: 41% and C6: 57%)). Recoveries of the other pollutants were higher than 80%. Precision, expressed as relative standard deviation, was in the range from 1% to 16%. Method detection limits were in the range 0.001-1.126 µg L(-1), for surface water, and 0.001-1.446 µg L(-1) for tap water. No important matrix effect was observed. PMID:26078168

  19. Urinary levels of bisphenol A, benzophenones and parabens in Tunisian women: A pilot study.

    PubMed

    Jiménez-Díaz, I; Artacho-Cordón, F; Vela-Soria, F; Belhassen, H; Arrebola, J P; Fernández, M F; Ghali, R; Hedhili, A; Olea, N

    2016-08-15

    Bisphenol A (BPA), benzophenones and parabens are commonly used in the production of polycarbonate plastics, as UV-filters and as antimicrobial preservatives, respectively, and they are thought to exhibit endocrine disrupting properties. Exposure to these compounds remains poorly characterized in developing countries, despite the fact that certain behaviors related to westernization have the potential to influence exposure. The aim of this pilot study was to measure urinary concentrations of BPA, six different benzophenones and four parabens in 34 Tunisian women. In addition, we identified some socio-demographic and dietary predictors of exposure to these compounds. Chemical analyses were carried out by dispersive liquid-liquid microextraction (DLLME) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Detection frequencies of methylparaben (MP), ethylparaben (EP) and propylparaben (PP) ranged between 67.6 and 94.1%. Butylparaben (BP) was found in 38.2% of the analyzed samples; BPA in 64.7%; and benzophenone-1 (BP-1) and benzophenone-3 (BP-3) were detected in 91.2 and 64.7% of the analyzed samples, respectively. Urinary geometric mean concentrations of MP, EP, PP, and BP were 30.1, 1.4, 2.0 and 0.5ngmL(-1), respectively. Geometric mean concentrations of BPA, BP-1, and BP-3 were 0.4, 1.3 and 1.1ngmL(-1), respectively. Our results suggest that Tunisian women are widely exposed to BPA, parabens and some benzophenones. Further studies on the general Tunisian population are needed in order to assess the levels of exposure to these compounds and to identify sources of exposure and population groups at higher risk. PMID:27096629

  20. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  1. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  2. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  3. 21 CFR 184.1670 - Propylparaben.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or may be examined at the National Archives and Records Administration (NARA). For information on the availability of this...

  4. 21 CFR 184.1670 - Propylparaben.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or may be examined at the National Archives and Records Administration (NARA). For information on the availability of this...

  5. 21 CFR 184.1670 - Propylparaben.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-hydroxybenzoate. It is produced by the n-propanol esterification of p-hydroxybenzoic acid in the presence of sulfuric acid, with subsequent distillation. (b) The ingredient meets the specifications of the...

  6. 21 CFR 184.1670 - Propylparaben.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...)(2) of this chapter. (d) The ingredient is used in food at levels not to exceed good manufacturing practices. Current good manufacturing practice results in a maximum level of 0.1 percent in food. (e)...

  7. 21 CFR 184.1490 - Methylparaben.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or may be examined at the National Archives and Records Administration (NARA). For information on the availability of this...

  8. 21 CFR 184.1490 - Methylparaben.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... National Academy Press, 2101 Constitution Ave. NW., Washington, DC 20418, or may be examined at the National Archives and Records Administration (NARA). For information on the availability of this...

  9. 21 CFR 184.1490 - Methylparaben.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-hydroxybenzoate. It is produced by the methanol esterification of p-hydroxybenzoic acid in the presence of sulfuric acid, with subsequent distillation. (b) The ingredient meets the specifications of the...

  10. 21 CFR 184.1490 - Methylparaben.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...)(2) of this chapter. (d) The ingredient is used in food at levels not to exceed good manufacturing practices. Current good manufacturing practice results in a maximum level of 0.1 percent in food. (e)...

  11. Hydrolysis of 4-Hydroxybenzoic Acid Esters (Parabens) and Their Aerobic Transformation into Phenol by the Resistant Enterobacter cloacae Strain EM

    PubMed Central

    Valkova, Nelly; Lépine, François; Valeanu, Loredana; Dupont, Maryse; Labrie, Louisette; Bisaillon, Jean-Guy; Beaudet, Réjean; Shareck, François; Villemur, Richard

    2001-01-01

    Enterobacter cloacae strain EM was isolated from a commercial dietary mineral supplement stabilized by a mixture of methylparaben and propylparaben. It harbored a high-molecular-weight plasmid and was resistant to high concentrations of parabens. Strain EM was able to grow in liquid media containing similar amounts of parabens as found in the mineral supplement (1,700 and 180 mg of methyl and propylparaben, respectively, per liter or 11.2 and 1.0 mM) and in very high concentrations of methylparaben (3,000 mg liter−1, or 19.7 mM). This strain was able to hydrolyze approximately 500 mg of methyl-, ethyl-, or propylparaben liter−1 (3 mM) in less than 2 h in liquid culture, and the supernatant of a sonicated culture, after a 30-fold dilution, was able to hydrolyze 1,000 mg of methylparaben liter−1 (6.6 mM) in 15 min. The first step of paraben degradation was the hydrolysis of the ester bond to produce 4-hydroxybenzoic acid, followed by a decarboxylation step to produce phenol under aerobic conditions. The transformation of 4-hydroxybenzoic acid into phenol was stoichiometric. The conversion of approximately 500 mg of parabens liter−1 (3 mM) to phenol in liquid culture was completed within 5 h without significant hindrance to the growth of strain EM, while higher concentrations of parabens partially inhibited its growth. PMID:11375144

  12. LC for analysis of two sustained-release mixtures containing cough cold suppressant drugs.

    PubMed

    El-Gindy, Alaa; Sallam, Shehab; Abdel-Salam, Randa A

    2010-07-01

    A liquid chromatographic method was applied for the analysis of two sustained-release mixtures containing dextromethorphane hydrobromide, carbinoxamine maleate with either phenylephrine hydrochloride in pharmaceutical capsules (Mix 1) or phenyl-propanolamine, methylparaben, and propylparaben, which bonds as a drug base to ion exchange resin in pharmaceutical syrup (Mix 2). The method was used for their simultaneous determination using a CN column with a mobile phase consisting of acetonitrile-12 mM ammonium acetate in the ratio of 60:40 (v/v, pH 6.0) for Mix 1 and 45:55 (v/v, pH 6.0) for Mix 2. PMID:20822669

  13. Liquid chromatographic determination of clobetasone-17-butyrate in ointments.

    PubMed

    Patel, A G; Patel, R B; Patel, M R

    1990-01-01

    A liquid chromatographic (LC) method has been developed for determination of clobetasone-17-butyrate in ointment using clobetasone propionate as an internal standard. Separation was carried out on a C18 reverse-phase column using water-methanol as a mobile phase. Methylparaben and propylparaben (both sodium salt) used as preservatives did not interfere with separation. Compounds are detected photometrically at 235 nm. Mean assay results for 0.05% commercial ointments were 100.36% (n = 5). Mean recovery of clobetasone-17-butyrate added to commercial ointment was 99.89%. PMID:2289922

  14. Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children.

    PubMed

    Larsson, Kristin; Ljung Björklund, Karin; Palm, Brita; Wennberg, Maria; Kaj, Lennart; Lindh, Christian H; Jönsson, Bo A G; Berglund, Marika

    2014-12-01

    Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood. The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6-11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother-child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors. There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 μg/L; ΣDiNP 37.8 μg/L; MBzP 19.9 μg/L; MnBP 76.9 μg/L) than the mothers (ΣDEHP 38.4 μg/L; ΣDiNP 33.8 μg/L; MBzP 12.8 μg/L; MnBP 63.0 μg/L). Conversely, the mother's levels of parabens (MetP 37.8 μg/L; ProP 13.9 μg/L) and MEP (43.4 μg/L) were higher than the children's levels of parabens (MetP 6.8 μg/L; ProP 2.1 μg/L) and MEP (28.8 μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p=<0.001; MnBP p=0.001-0.002), which is probably due to higher presence of PVC in floorings and wall coverings in this area, whereas

  15. Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children

    PubMed Central

    Larsson, Kristin; Ljung Björklund, Karin; Palm, Brita; Wennberg, Maria; Kaj, Lennart; Lindh, Christian H.; Jönsson, Bo A.G.; Berglund, Marika

    2014-01-01

    Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood. The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6–11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother–child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors. There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 μg/L; ΣDiNP 37.8 μg/L; MBzP 19.9 μg/L; MnBP 76.9 μg/L) than the mothers (ΣDEHP 38.4 μg/L; ΣDiNP 33.8 μg/L; MBzP 12.8 μg/L; MnBP 63.0 μg/L). Conversely, the mother's levels of parabens (MetP 37.8 μg/L; ProP 13.9 μg/L) and MEP (43.4 μg/L) were higher than the children's levels of parabens (MetP 6.8 μg/L; ProP 2.1 μg/L) and MEP (28.8 μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p = < 0.001; MnBP p = 0.001–0.002), which is probably due to higher presence of PVC in floorings and wall

  16. Contents of methyl-, ethyl-, propyl-, butyl- and benzylparaben in cosmetic products.

    PubMed

    Rastogi, S C; Schouten, A; de Kruijf, N; Weijland, J W

    1995-01-01

    The contents of methyl-, ethyl-, propyl-, butyl- and benzylparaben in 215 cosmetic products have been determined to elucidate the concentration and frequency of use of these parabens in cosmetic products, and to monitor whether the products complied with the Danish and EEC regulations. The results showed that 77% of the products investigated contained 0.01%-0.87% parabens. Nearly all (99%) of the leave-on cosmetics and 77% of rinse-off cosmetics were found to contain parabens. A maximum of 0.32% methyl- and propylparaben, 0.19% ethylparaben, and 0.07% butyl- and benzylparaben were present in paraben-positive cosmetics. A preferential use of methyl-/ethyl-/propyl-/butyl-/benzylparaben in various groups of cosmetic products was revealed. PMID:7720367

  17. "Parabenoia" Debunked, or "Who's Afraid of Parabens?".

    PubMed

    Sasseville, Denis; Alfalah, Maisa; Lacroix, Jean-Philip

    2015-01-01

    Parabens have been used as preservatives in foods, injectables, and topical preparations for nearly 10 decades. Present in nature, rapidly metabolized by skin and liver enzymes, they have an excellent safety record. However, in the past 15 years, they have been under scrutiny for their alleged estrogenic and antiandrogenic effects, as well as their putative role in promoting cancerogenesis through endocrine disruption. Scientific articles supporting these assertions have led the European Community to ban or restrict the use of some parabens. Despite that methylparaben and ethylparaben have negligible endocrine disruption activity, the food, pharmaceutical, and cosmetic industries are under pressure from scare campaigns in the media and are responding by replacing parabens with other biocides that cause multiple cases, and even worldwide epidemics, of allergic contact sensitization. In the present review, we present a balanced account of the published literature about the metabolism and potential toxicology of parabens. PMID:26551603

  18. Design Space Approach for Preservative System Optimization of an Anti-Aging Eye Fluid Emulsion.

    PubMed

    Lourenço, Felipe Rebello; Francisco, Fabiane Lacerda; Ferreira, Márcia Regina Spuri; Andreoli, Terezinha De Jesus; Löbenberg, Raimar; Bou-Chacra, Nádia

    2015-01-01

    The use of preservatives must be optimized in order to ensure the efficacy of an antimicrobial system as well as the product safety. Despite the wide variety of preservatives, the synergistic or antagonistic effects of their combinations are not well established and it is still an issue in the development of pharmaceutical and cosmetic products. The purpose of this paper was to establish a space design using a simplex-centroid approach to achieve the lowest effective concentration of 3 preservatives (methylparaben, propylparaben, and imidazolidinyl urea) and EDTA for an emulsion cosmetic product. Twenty-two formulae of emulsion differing only by imidazolidinyl urea (A: 0.00 to 0.30% w/w), methylparaben (B: 0.00 to 0.20% w/w), propylparaben (C: 0.00 to 0.10% w/w) and EDTA (D: 0.00 to 0.10% w/w) concentrations were prepared. They were tested alone and in binary, ternary and quaternary combinations. Aliquots of these formulae were inoculated with several microorganisms. An electrochemical method was used to determine microbial burden immediately after inoculation and after 2, 4, 8, 12, 24, 48, and 168 h. An optimization strategy was used to obtain the concentrations of preservatives and EDTA resulting in a most effective preservative system of all microorganisms simultaneously. The use of preservatives and EDTA in combination has the advantage of exhibiting a potential synergistic effect against a wider spectrum of microorganisms. Based on graphic and optimization strategies, we proposed a new formula containing a quaternary combination (A: 55%; B: 30%; C: 5% and D: 10% w/w), which complies with the specification of a conventional challenge test. A design space approach was successfully employed in the optimization of concentrations of preservatives and EDTA in an emulsion cosmetic product. PMID:26517141

  19. Resolution of five-component mixture using mean centering ratio and inverse least squares chemometrics

    PubMed Central

    2013-01-01

    Background A comparative study of the use of mean centering of ratio spectra and inverse least squares for the resolution of paracetamol, methylparaben, propylparaben, chlorpheniramine maleate and pseudoephedrine hydrochloride has been achieved showing that the two chemometric methods provide a good example of the high resolving power of these techniques. Method (I) is the mean centering of ratio spectra which depends on using the mean centered ratio spectra in four successive steps that eliminates the derivative steps and therefore the signal to noise ratio is improved. The absorption spectra of prepared solutions were measured in the range of 220–280 nm. Method (II) is based on the inverse least squares that depend on updating developed multivariate calibration model. The absorption spectra of the prepared mixtures in the range 230–270 nm were recorded. Results The linear concentration ranges were 0–25.6, 0–15.0, 0–15.0, 0–45.0 and 0–100.0 μg mL-1 for paracetamol, methylparaben, propylparaben, chlorpheniramine maleate and pseudoephedrine hydrochloride, respectively. The mean recoveries for simultaneous determination were between 99.9-101.3% for the two methods. The two developed methods have been successfully used for prediction of five-component mixture in Decamol Flu syrup with good selectivity, high sensitivity and extremely low detection limit. Conclusion No published method has been reported for simultaneous determination of the five components of this mixture so that the results of the mean centering of ratio spectra method were compared with those of the proposed inverse least squares method. Statistical comparison was performed using t-test and F-ratio at P = 0.05. There was no significant difference between the results. PMID:24028626

  20. GC-MS determination of parabens, triclosan and methyl triclosan in water by in situ derivatisation and stir-bar sorptive extraction.

    PubMed

    Casas Ferreira, Ana María; Möder, Monika; Fernández Laespada, María Esther

    2011-01-01

    Stir-bar sorptive extraction in combination with an in situ derivatisation reaction and thermal desorption-gas chromatography-mass spectrometry was successfully applied to determine parabens (methylparaben, isopropylparaben, n-propylparaben, butylparaben and benzylparaben), triclosan and methyltriclosan in water samples. This approach improves both the extraction efficiency and the sensitivity in the GC in a simple way since the derivatisation reaction occurs at the same time as the extraction procedure. The in situ derivatisation reaction was carried out with acetic anhydride under alkaline conditions. Thermal desorption parameters (cryofocusing temperature, desorption flow, desorption time, desorption temperature) were optimised using a Box-Behnken experimental design. All the analytes gave recoveries higher than 79%, except methylparaben (22%). The method afforded detection limits between 0.64 and 4.12 ng/L, with good reproducibility and accuracy values. The feasibility of the method for the determination of analytes in water samples was checked in tap water and untreated and treated wastewater. PMID:21046080

  1. Simultaneous, stability indicating, HPLC-DAD determination of guaifenesin and methyl and propyl-parabens in cough syrup.

    PubMed

    Grosa, Giorgio; Del Grosso, Erika; Russo, Roberta; Allegrone, Gianna

    2006-06-01

    A stability indicating high performance liquid chromatography procedure has been developed for the simultaneous determination of guaifenesin (GUA), methyl p-hydroxybenzoate (MHB) and propyl p-hydroxybenzoate (PHB) in a commercial cough syrup dosage form. The method was specific and stability indicating as chromatographic conditions were selected to provide adequate separation of GUA, MHB and PHB from the putative degradation products guaiacol (GUAI) and p-hydroxybenzoic acid (HBA) as well as from excipients. The isocratic separation and quantitation were achieved within 17 min on a 150-mm column with an ether-linked phenyl stationary phase and a hydrophilic endcapping. The mobile phase was constituted of eluant A: aqueous phosphate buffer (pH 3.0, 10 mM)/acetonitrile 25/75 (v/v) and eluant B:methanol; the A:B ratio was 85:15 (v/v) with a flow rate 1 ml min-1 and detection of analytes at 254 and 276 nm. The method showed good linearity for the GUA-MHB-PHB mixture in the 95-285, 4-12, and 1-3 microg ml-1 ranges, respectively, being all the square of the correlation coefficients greater than 0.999. The interday R.S.D.s were 1.17, 1.14, and 0.91%, for GUA, MHB, and PHP, respectively. The method demonstrated also to be accurate; indeed the average recoveries, at 100% of the target assay concentration, were 100.5, 100.3, and 100.7% with relative standard deviations of 0.8, 0.7, and 0.4% for GUA, MHB, and PHB, respectively, from laboratory prepared samples. The applicability of the method was evaluated in commercial dosage form analysis as well as in stability studies. PMID:16497471

  2. Hydrolysis of a series of parabens by skin microsomes and cytosol from human and minipigs and in whole skin in short-term culture.

    PubMed

    Jewell, Christopher; Prusakiewicz, Jeffery J; Ackermann, Chrisita; Payne, N Ann; Fate, Gwendolyn; Voorman, Richard; Williams, Faith M

    2007-12-01

    Parabens are esters of 4-hydroxybenzoic acid and used as anti-microbial agents in a wide variety of toiletries, cosmetics and pharmaceuticals. It is of interest to understand the dermal absorption and hydrolysis of parabens, and to evaluate their disposition after dermal exposure and their potential to illicit localised toxicity. The use of minipig as a surrogate model for human dermal metabolism and toxicity studies, justifies the comparison of paraben metabolism in human and minipig skin. Parabens are hydrolysed by carboxylesterases to 4-hydroxybenzoic acid. The effects of the carboxylesterase inhibitors paraoxon and bis-nitrophenylphosphate provided evidence of the involvement of dermal carboxylesterases in paraben hydrolysis. Loperamide, a specific inhibitor of human carboxylesterase-2 inhibited butyl- and benzylparaben hydrolysis in human skin but not methylparaben or ethylparaben. These results show that butyl- and benzylparaben are more selective substrates for human carboxylesterase-2 in skin than the other parabens examined. Parabens applied to the surface of human or minipig skin were absorbed to a similar amount and metabolised to 4-hydroxybenzoic acid during dermal absorption. These results demonstrate that the minipig is a suitable model for man for assessing dermal absorption and hydrolysis of parabens, although the carboxylesterase profile in skin differs between human and minipig. PMID:17889094

  3. Hydrolysis of a series of parabens by skin microsomes and cytosol from human and minipigs and in whole skin in short-term culture

    SciTech Connect

    Jewell, Christopher; Prusakiewicz, Jeffery J.; Ackermann, Chrisita; Payne, N. Ann; Fate, Gwendolyn; Voorman, Richard; Williams, Faith M.

    2007-12-01

    Parabens are esters of 4-hydroxybenzoic acid and used as anti-microbial agents in a wide variety of toiletries, cosmetics and pharmaceuticals. It is of interest to understand the dermal absorption and hydrolysis of parabens, and to evaluate their disposition after dermal exposure and their potential to illicit localised toxicity. The use of minipig as a surrogate model for human dermal metabolism and toxicity studies, justifies the comparison of paraben metabolism in human and minipig skin. Parabens are hydrolysed by carboxylesterases to 4-hydroxybenzoic acid. The effects of the carboxylesterase inhibitors paraoxon and bis-nitrophenylphosphate provided evidence of the involvement of dermal carboxylesterases in paraben hydrolysis. Loperamide, a specific inhibitor of human carboxylesterase-2 inhibited butyl- and benzylparaben hydrolysis in human skin but not methylparaben or ethylparaben. These results show that butyl- and benzylparaben are more selective substrates for human carboxylesterase-2 in skin than the other parabens examined. Parabens applied to the surface of human or minipig skin were absorbed to a similar amount and metabolised to 4-hydroxybenzoic acid during dermal absorption. These results demonstrate that the minipig is a suitable model for man for assessing dermal absorption and hydrolysis of parabens, although the carboxylesterase profile in skin differs between human and minipig.

  4. An evaluation of preservative adsorption onto nylon membrane filters.

    PubMed

    Guilfoyle, D E; Roos, R; Carito, S L

    1990-01-01

    Pharmaceutical drug products often contain antimicrobial agents as a preservative in their formulation. These excipients are required to destroy or impede the growth of microorganisms that inadvertently enter the product during manufacturing. Unfortunately, these preservatives may also interfere with microbiological assays used to determine product sterility or bioburden levels. The extent of interference by these preservatives can be quite significant, but varies depending on the method used. The most frequently used method for testing parenteral drug products is the membrane filtration technique. Membrane filters are composed of a wide variety of materials such as cellulose, polycarbonate, acrylic polypropylene, Teflon, and nylon. This study evaluated the adsorption characteristics that nylon filters, obtained from five different manufacturers, had on the filtration of solutions of four different antimicrobial compounds (phenol, methylparaben, propylparaben, and benzalkonium chloride). The adsorption properties were determined using both HPLC and microbiological assay techniques. The data revealed that there was a wide range in the amounts of antimicrobial agent (2.3 to 94.1%) bound to the membrane filters when direct product filtration was used without a subsequent rinse step. However, when a rinse step is included, only propylparaben showed any significant "true" adsorption (less than 1 to 33.3%), but showed only marginal bacterial inhibition. Interestingly, the microbiological assays indicated that with a saline rinse step, only benzalkonium chloride was lethal for the two challenge organisms even though the percent adsorbed as measured by HPLC was below 1%. This discrepancy is significant because it demonstrates the analytical limitation when using HPLC to detect minimal concentrations of benzalkonium chloride that may be deleterious to microorganisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2277319

  5. Occurrence of acidic pharmaceuticals and personal care products in Turia River Basin: from waste to drinking water.

    PubMed

    Carmona, Eric; Andreu, Vicente; Picó, Yolanda

    2014-06-15

    The occurrence of 21 acidic pharmaceuticals, including illicit drugs, and personal care products (PPCPs) in waste, surface and drinking water and in sediments of the Turia River Basin (Valencia, Spain) was studied. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the determination of these PPCPs with electrospray (ESI) in negative ionization (NI) mode. Ammonium fluoride in the mobile phase improved ionization efficiency by an average increase in peak area of 5 compared to ammonium formate or formic acid. All studied compounds were detected and their concentration was waste water>surface water>drinking water. PPCPs were in waste water treatment plants (WWTPs) influents up to 7.26μgL(-1), dominated by ibuprofen, naproxen and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCOOH). WWTPs were highly effective in removing most of them, with an average removal rate of >90%. PPCPs were still detected in effluents in the 6.72-940ngL(-1) range, with the THCOOH, triclocarban, gemfibrozil and diclofenac as most prevalent. Similarly, diclofenac, gemfibrozil, ibuprofen, naproxen and propylparaben were detected quite frequently from the low ngL(-1) range to 7μgL(-1) in the surface waters of Turia River. Ibuprofen, methylparaben, salicylic acid and tetrahydrocannabinol (THC) were at concentrations up to 0.85ngg(-1) d.w. in sediments. The discharge of WWTP as well as of non-treated waters to this river is a likely explanation for the significant amount of PPCPs detected in surface waters and sediments. Mineral and tap waters also presented significant amounts (approx. 100ngL(-1)) of ibuprofen, naproxen, propylparaben and butylparaben. The occurrence at trace levels of several PPCPs in drinking water raises concerns about possible implications for human health. PMID:24686145

  6. New sorbent in the dispersive solid phase extraction step of quick, easy, cheap, effective, rugged, and safe for the extraction of organic contaminants in drinking water treatment sludge.

    PubMed

    Cerqueira, Maristela B R; Caldas, Sergiane S; Primel, Ednei G

    2014-04-01

    Recent studies have shown a decrease in the concentration of pesticides, pharmaceuticals and personal care products (PCPs) in water after treatment. A possible explanation for this phenomenon is that these compounds may adhere to the sludge; however, investigation of these compounds in drinking water treatment sludge has been scarce. The sludge generated by drinking water treatment plants during flocculation and decantation steps should get some special attention not only because it has been classified as non-inert waste but also because it is a very complex matrix, consisting essentially of inorganic (sand, argil and silt) and organic (humic substances) compounds. In the first step of this study, three QuEChERS methods were used, and then compared, for the extraction of pesticides (atrazine, simazine, clomazone and tebuconazole), pharmaceuticals (amitriptyline, caffeine, diclofenac and ibuprofen) and PCPs (methylparaben, propylparaben, triclocarban and bisphenol A) from drinking water treatment sludge. Afterwards, the study of different sorbents in the dispersive solid phase extraction (d-SPE) step was evaluated. Finally, a new QuEChERS method employing chitin, obtained from shrimp shell waste, was performed in the d-SPE step. After having been optimized, the method showed limits of quantification (LOQ) between 1 and 50 μg kg(-1) and the analytical curves showed r values higher than 0.98, when liquid chromatography tandem mass spectrometry was employed. Recoveries ranged between 50 and 120% with RSD≤15%. The matrix effect was evaluated and compensated with matrix-matched calibration. The method was applied to drinking water treatment sludge samples and methylparaben and tebuconazole were found in concentration

  7. Electrochemical conversion of micropollutants in gray water.

    PubMed

    Butkovskyi, Andrii; Jeremiasse, Adriaan W; Hernandez Leal, Lucia; van der Zande, Ton; Rijnaarts, Huub; Zeeman, Grietje

    2014-01-01

    Electrochemical conversion of micropollutants in real gray water effluent was studied for the first time. Six compounds that are frequently found in personal care and household products, namely methylparaben, propylparaben, bisphenol A, triclosan, galaxolide, and 4- methylbenzilidene camphor (4-MBC), were analyzed in the effluent of the aerobic gray water treatment system in full operation. The effluent was used for lab-scale experiments with an electrochemical cell operated in batch mode. Three different anodes and five different cathodes have been tested. Among the anodes, Ru/Ir mixed metal oxide showed the best performance. Ag and Pt cathodes worked slightly better than Ti and mixed metal oxide cathodes. The compounds that contain a phenolic ring (parabens, bisphenol A, and triclosan) were completely transformed on this anode at a specific electric charge Q = 0.03 Ah/L. The compounds, which contain a benzene ring and multiple side methyl methyl groups (galaxolide, 4-MBC) required high energy input (Q ≤ 0.6 Ah/L) for transformation. Concentrations of adsorbable organohalogens (AOX) in the gray water effluent increased significantly upon treatment for all electrode combinations tested. Oxidation of gray water on mixed metal oxide anodes could not be recommended as a post-treatment step for gray water treatment according to the results of this study. Possible solutions to overcome disadvantages revealed within this study are proposed. PMID:24364736

  8. Investigation of parabens in commercial cosmetics for children in Beijing, China.

    PubMed

    Wang, Ping; Li, Jie; Tian, Hanmei; Ding, Xiaojing

    2013-01-01

    Parabens are one of the most common preservatives in cosmetics. Because allergenicity and cytotoxicity potential values are major aspects of preservative safety and parabens are xenoestrogens, safety levels of parabens have been restricted in "Hygienic Standard for Cosmetics" (2007 edition) by the Ministry of Public Health of China, and a high-performance liquid chromatography (HPLC) for the simultaneous determination of parabens is recommended. To investigate whether the commonly used parabens in children's cosmetics were at a safety level, 105 cosmetics for children were randomly purchased from the local market in Beijing and analyzed by the proposed HPLC method. The detection rate of methylparaben was the highest and the next was propylparaben. Among the 105 samples, two or more kinds of parabens were detected in 72 samples with concentrations ranging from 0.02% to 0.75%; 18 samples contained one kind of paraben with concentrations ranging from 0.002% to 0.06%. In this study, the contents of parabens in the 105 samples were all below the restricted levels. PMID:23449132

  9. Determination of parabens in serum by liquid chromatography-tandem mass spectrometry: Correlation with lipstick use.

    PubMed

    Tahan, Gabriella Padovani; Santos, Nayara de Kássia Souza; Albuquerque, Ana Carolina; Martins, Isarita

    2016-08-01

    Parabens are the most widely used preservative and are considered to be relatively safe compounds. However, studies have demonstrated that they may have estrogenic activity, and there is ongoing debate regarding the safety and potential cancer risk of using products containing these compounds. In the present work, liquid chromatography-tandem mass spectrometry was applied to determine methylparaben and propylparaben concentrations in serum, and the results were correlated with lipstick application. Samples were analyzed using liquid-liquid extraction, followed by liquid chromatography-tandem mass spectrometry. The validation results demonstrated the linearity of the method over a range of 1-20 ng/mL, in addition to the method's precision and accuracy. A statistically significant difference was demonstrated between serum parabens in women who used lipstick containing these substances compared with those not using this cosmetic (p = 0.0005 and 0.0016, respectively), and a strong association was observed between serum parabens and lipstick use (Spearman correlation = 0.7202). PMID:27154569

  10. Occurrence, fate and behavior of parabens in aquatic environments: a review.

    PubMed

    Haman, Camille; Dauchy, Xavier; Rosin, Christophe; Munoz, Jean-François

    2015-01-01

    Parabens are esters of para-hydroxybenzoic acid, with an alkyl (methyl, ethyl, propyl, butyl or heptyl) or benzyl group. They are mainly used as preservatives in foodstuffs, cosmetics and pharmaceutical drugs. Parabens may act as weak endocrine disrupter chemicals, but controversy still surrounds the health effects of these compounds. Despite being used since the mid-1920s, it was only in 1996 that the first analytical results of their occurrence in water were published. Considered as emerging contaminants, it is useful to review the knowledge acquired over the last decade regarding their occurrence, fate and behavior in aquatic environments. Despite treatments that eliminate them relatively well from wastewater, parabens are always present at low concentration levels in effluents of wastewater treatment plants. Although they are biodegradable, they are ubiquitous in surface water and sediments, due to consumption of paraben-based products and continuous introduction into the environment. Methylparaben and propylparaben predominate, reflecting the composition of paraben mixtures in common consumer products. Being compounds containing phenolic hydroxyl groups, parabens can react readily with free chlorine, yielding halogenated by-products. Chlorinated parabens have been detected in wastewater, swimming pools and rivers, but not yet in drinking water. These chlorinated by-products are more stable and persistent than the parent species and further studies are needed to improve knowledge regarding their toxicity. PMID:25462712

  11. Preventing sexual transmission of HIV: anti-HIV bioregulatory and homeostatic components of commercial sexual lubricants.

    PubMed

    Nguyen, D; Lee, H; Poast, J; Cloyd, M W; Baron, S

    2004-01-01

    Certain safe over-the-counter (OTC) sexual lubricants such as Astroglide, KY Liquid, Replens, Vagisil, ViAmor, and Wet Stuff inhibit both cell-free HIV and the production of HIV by infected leukocytes in vitro even in the presence of seminal fluid. To identify which components of the lubricants were active against HIV, we tested five components (glycerin, methylparaben, propylparaben, polyquaternium-32, and propylene glycol). The paraben preservatives and propylene glycol in the lubricants did not inhibit HIV, while the common natural homeostatic metabolite, glycerin, and the thickener polyquaternium-32 did strongly inactivate infectious HIV and HIV-infected leukocytes. Activity against HIV and HIV-infected cells by glycerin was stable through 24 hours at 37 degrees C. Glycerin and polyquaternium-32 were active at minimum concentrations of approximately 2% and 0.01%, respectively--well within the highest FDA safety guidelines. Both active components disrupted infected leukocytes within 5 minutes which resulted in inhibition of infectious HIV production by infected leukocytes of greater than 25 to 100-fold. These components do not disrupt vaginal epithelial cells in vivo. These components also rapidly inactivate cell-free HIV by 10- to 30-fold. Thus, we may conclude that the active components of the OTC lubricants are glycerin and polyquaternium-32. Using these components, OTC sexual lubricants could be reformulated to optimize their anti-HIV activity. Furthermore, clinical trials of these lubricants and components seem to be indicated because of their FDA safety level, wide availability, and low cost. PMID:15786693

  12. Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic

    PubMed Central

    Braun, Joe M.; Just, Allan C.; Williams, Paige L.; Smith, Kristen W.; Calafat, Antonia M.; Hauser, Russ

    2014-01-01

    Parabens and phthalates are potential endocrine disruptors frequently used in personal care/beauty products, and the developing fetus may be sensitive to these chemicals. We measured urinary butyl-paraben (BP), methyl-paraben (MP), propyl-paraben (PP), mono-n-butyl phthalate (MBP), and monoethyl phthalate (MEP) concentrations up to three times in 177 pregnant women from a fertility clinic in Boston MA. Using linear mixed models, we examined the relationship between self-reported personal care product use in the previous 24 hours and urinary paraben and phthalate metabolite concentrations. Lotion, cosmetic, and cologne/perfume use were associated with the greatest increases in the molar sum of phthalate metabolite and paraben concentrations, although the magnitude of individual biomarker increases varied by product used. For example, women who used lotion had BP concentrations 111% higher (95% confidence interval [CI]:41%, 216%) than non-users, while their MBP concentrations were only 28% higher (CI:2%, 62%). Women using/cologne/perfume had MEP concentrations 167% (CI:98%, 261%) higher than non-users, but BP concentrations were similar. We observed a monotonic dose-response relationship between the total number of products used and urinary paraben and phthalate metabolite concentrations. These results suggest that questionnaire data may be useful for assessing exposure to a mixture of chemicals from personal care products during pregnancy. PMID:24149971

  13. Liquid chromatography and chemometric-assisted spectrophotometric methods for the analysis of two multicomponent mixtures containing cough suppressant drugs.

    PubMed

    El-Gindy, Alaa; Emara, Samy; Mesbah, Mostafa K; Hadad, Ghada M

    2005-01-01

    Three methods were applied for the analysis of 2 multicomponent mixtures containing dextromethorphan hydrobromide, phenylephrine hydrochloride, chlorpheniramine maleate, methylparaben, and propylparaben, together with either sodium benzoate (Mix 1) or ephedrine hydrochloride and benzoic acid (Mix 2). In the first method, liquid chromatography was used for their simultaneous determination using an ODS column with a mobile phase consisting of acetonitrile-phosphate buffer, pH 2.7 (40 + 60, v/v), containing 5mM heptanesulfonic acid sodium salt and ultraviolet (UV) detection at 214 nm. Also, 2 chemometric methods, principal component regression, and partial least squares were used. For both chemometric calibrations, a concentration set of the mixture consisting of each compound in each mixture was prepared in distilled water. The absorbance data in the UV spectra were measured for the 76 or 71 wavelength points in the spectral region 210-240 or 210-224 nm considering the intervals of deltagamma = 0.4 or 0.2 nm for Mix 1 and Mix 2, respectively. The 2 chemometric methods did not require any separation step. These methods were successfully applied for the analysis of the 2 multicomponent combinations in synthetic mixtures and in commercial syrups, and the results were compared with each other. PMID:16152922

  14. A Rapid, Stability Indicating RP-UPLC Method for Simultaneous Determination of Ambroxol Hydrochloride, Cetirizine Hydrochloride and Antimicrobial Preservatives in Liquid Pharmaceutical Formulation.

    PubMed

    Trivedi, Rakshit Kanubhai; Patel, Mukesh C; Jadhav, Sushant B

    2011-09-01

    A stability indicating reversed phase ultra performance liquid chromatography (RP-UPLC) method was developed for simultaneous determination of ambroxol hydrochloride (AMB), cetirizine hydrochloride (CTZ), methylparaben (MP) and propylparaben (PP) in liquid pharmaceutical formulation. The desired chromatographic separation was achieved on an Agilent Eclipse plus C18, 1.8 μm (50 × 2.1 mm) column using gradient elution at 237 nm detector wavelength. The optimized mobile phase consists of a mixture of 0.01 M phosphate buffer and 0.1 % triethylamine as a solvent-A and acetonitrile as a solvent-B. The developed method separates AMB, CTZ, MP and PP in presence of twelve known impurities/degradation products and one unknown degradation product within 3.5 min. Stability indicating capability was established by forced degradation experiments and seperation of known and unknown degradation products. The lower limit of quantification was established for AMB, CTZ, MP and PP. The developed RP-UPLC method was validated according to the International Conference on Harmonization (ICH) guidelines. This validated method is applied for simultaneous estimation of AMB, CTZ, MP and PP in commercially available syrup samples. Further, the method can be extended for estimation of AMB, CTZ, MP, PP and levo-cetirizine (LCTZ) in various commercially available dosage forms. PMID:21886901

  15. A Rapid, Stability Indicating RP-UPLC Method for Simultaneous Determination of Ambroxol Hydrochloride, Cetirizine Hydrochloride and Antimicrobial Preservatives in Liquid Pharmaceutical Formulation

    PubMed Central

    Trivedi, Rakshit Kanubhai; Patel, Mukesh C.; Jadhav, Sushant B.

    2011-01-01

    A stability indicating reversed phase ultra performance liquid chromatography (RP-UPLC) method was developed for simultaneous determination of ambroxol hydrochloride (AMB), cetirizine hydrochloride (CTZ), methylparaben (MP) and propylparaben (PP) in liquid pharmaceutical formulation. The desired chromatographic separation was achieved on an Agilent Eclipse plus C18, 1.8 μm (50 × 2.1 mm) column using gradient elution at 237 nm detector wavelength. The optimized mobile phase consists of a mixture of 0.01 M phosphate buffer and 0.1 % triethylamine as a solvent-A and acetonitrile as a solvent-B. The developed method separates AMB, CTZ, MP and PP in presence of twelve known impurities/degradation products and one unknown degradation product within 3.5 min. Stability indicating capability was established by forced degradation experiments and seperation of known and unknown degradation products. The lower limit of quantification was established for AMB, CTZ, MP and PP. The developed RP-UPLC method was validated according to the International Conference on Harmonization (ICH) guidelines. This validated method is applied for simultaneous estimation of AMB, CTZ, MP and PP in commercially available syrup samples. Further, the method can be extended for estimation of AMB, CTZ, MP, PP and levo-cetirizine (LCTZ) in various commercially available dosage forms. PMID:21886901

  16. Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic.

    PubMed

    Braun, Joe M; Just, Allan C; Williams, Paige L; Smith, Kristen W; Calafat, Antonia M; Hauser, Russ

    2014-01-01

    Parabens and phthalates are potential endocrine disruptors frequently used in personal care/beauty products, and the developing fetus may be sensitive to these chemicals. We measured urinary butyl-paraben (BP), methyl-paraben, propyl-paraben, mono-n-butyl phthalate (MBP), and monoethyl phthalate (MEP) concentrations up to three times in 177 pregnant women from a fertility clinic in Boston, MA. Using linear mixed models, we examined the relationship between self-reported personal care product use in the previous 24 h and urinary paraben and phthalate metabolite concentrations. Lotion, cosmetic, and cologne/perfume use were associated with the greatest increases in the molar sum of phthalate metabolite and paraben concentrations, although the magnitude of individual biomarker increases varied by product used. For example, women who used lotion had BP concentrations 111% higher (95% confidence interval (CI): 41%, 216%) than non-users, whereas their MBP concentrations were only 28% higher (CI: 2%, 62%). Women using cologne/perfume had MEP concentrations 167% (CI: 98%, 261%) higher than non-users, but BP concentrations were similar. We observed a monotonic dose-response relationship between the total number of products used and urinary paraben and phthalate metabolite concentrations. These results suggest that questionnaire data may be useful for assessing exposure to a mixture of chemicals from personal care products during pregnancy. PMID:24149971

  17. HPLC determination of calcium pantothenate and two preservatives in topical cream.

    PubMed

    Havlíková, L; Matysová, L; Nováková, L; Solich, P

    2006-05-01

    A RP-HPLC method for simultaneous determination of calcium pantothenate and two preservatives methylparaben and propylparaben present in topical cream was developed. Different analytical columns with various stationary phases were tested. During method development, Supelco Discovery C18 column (125 mmx4.0 mm, 5 microm) and Zorbax SB-CN column (150 mmx4.6 mm, 5 microm) were tested. Both were not convenient for analytical separation because of the co-elution of calcium pantothenate with dead volume, and problems with the peak-shape of all components. Good separation was achieved using Zorbax TSM (250 mmx4.6 mm, 5 microm) and Hypersil ODS column (250 mmx4.6 mm, 5 microm), the latter was finally used for the analysis. The analysis time was 12 min, at flow rate 0.7 ml min-1. Chromatography was performed using binary mobile phase composed of methanol and phosphoric acid, pH 2.5, 65:35 (v/v). UV detection was accomplished at 214 nm. The method was validated according to ICH guideline recommendations. The method is suitable for practical routine analysis of commercially produced topical pharmaceutical preparations. PMID:16473491

  18. Simultaneous determination of phenylephrine hydrochloride, guaifenesin, and chlorpheniramine maleate in cough syrup by gradient liquid chromatography.

    PubMed

    Amer, Sawsan M; Abbas, Samah S; Shehata, Mostafa A; Ali, Nahed M

    2008-01-01

    A simple and reliable high-performance liquid chromatographic method was developed for the simultaneous determination of mixture of phenylephrine hydrochloride (PHENYL), guaifenesin (GUAIF), and chlorpheniramine maleate (CHLO) either in pure form or in the presence of methylparaben and propylparaben in a commercial cough syrup dosage form. Separation was achieved on a C8 column using 0.005 M heptane sulfonic acid sodium salt (pH 3.4 +/- 0.1) and acetonitrile as a mobile phase by gradient elution at different flow rates, and detection was done spectrophotometrically at 210 nm. A linear relationship in the range of 30-180, 120-1800, and 10-60 microg/mL was obtained for PHENYL, GUAIF, and CHLO, respectively. The results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2002) method and showed that the proposed method is precise, accurate, and can be easily applied for the determination of the drugs under investigation in pure form and in cough syrup formulations. PMID:18476338

  19. New validated liquid chromatographic and chemometrics-assisted UV spectroscopic methods for the determination of two multicomponent cough mixtures in syrup.

    PubMed

    Hadad, Ghada M; El-Gindy, Alaa; Mahmoud, Waleed M M

    2008-01-01

    Multivariate spectrophotometric calibration and liquid chromatographic (LC) methods were applied to the determination of 2 multicomponent mixtures containing diprophylline, guaiphenesin, methylparaben, and propylparaben (Mixture 1), or clobutinol, orciprenaline, saccharin sodium, and sodium benzoate (Mixture 2). For the multivariate spectrophotometric calibration methods, principal component regression (PCR) and partial least-squares regression (PLS-1), a calibration set of the mixtures consisting of the components of each mixture was prepared in 0.1 M HCl. Analytical figures of merit such as sensitivity, selectivity, limit of quantitation, and limit of detection were determined for both PLS-1 and PCR. The LC separation was achieved on a reversed-phase C18 analytical column by using isocratic elution with 20 mM potassium dihydrogen phosphate, pH 3.3-acetonitrile (55 + 45, v/v) as the mobile phase and UV detection at 260 and 220 nm for Mixture 1 and Mixture 2, respectively. The proposed methods were validated and successfully applied to the analysis of pharmaceutical formulations and laboratory-prepared mixtures containing the 2 multicomponent combinations. PMID:18376584

  20. Antimicrobial preservative use in parenteral products: past and present.

    PubMed

    Meyer, Brian K; Ni, Alex; Hu, Binghua; Shi, Li

    2007-12-01

    The following review provides a comprehensive summary of antimicrobial preservatives that are commonly used in licensed parenteral products to date. The information reviewed includes the general properties of the preservatives, the doses and frequency of their use, the classes of the preserved products (peptide, protein, vaccine, and small molecule products), the interactions with other formulation components, and the criteria commonly used for their selection in parental product formulations. It was revealed that phenol and benzyl alcohol are the two most common antimicrobial preservatives used in peptide and protein products, while phenoxyethanol is the most frequently used preservative in vaccines. Benzyl alcohol or a combination of methylparaben and propylparaben are generally found in small molecule parenteral formulations. The key criteria for antimicrobial preservative selection are the preservative's dose, antimicrobial functionality, and effect on the active ingredient. Additionally, the use of spectroscopic techniques (circular dicroism (CD) and fluorescence) and differential scanning calorimetry (DSC) were identified as common techniques used in evaluating an antimicrobial preservative for its impact on the conformational stability of peptide, protein, and vaccine antigens. The future use of preservatives is also discussed, including antimicrobial agents such as peptides, and regulatory requirements for antimicrobial effectiveness testing. PMID:17722087

  1. Ecological risk assessment associated to the removal of endocrine-disrupting parabens and benzophenone-4 in wastewater treatment.

    PubMed

    Molins-Delgado, Daniel; Díaz-Cruz, M Silvia; Barceló, Damià

    2016-06-01

    The occurrence of four widely used and endocrine disrupting parabens (PBs) (methylparaben, propylparaben, butylparaben and benzylparaben) and a polar UV filter (benzophenone-4) were determined in influent and effluent wastewater from the 19 major wastewater treatment plants (WWTPs) of Catalonia, Spain. For their analysis an on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method was developed and validated. Laboratory analysis revealed high levels for both PBs and BP4, with maximum concentrations of 5700ngL(-1) and 1806ngL(-1), respectively, in influent samples, and 137ngL(-1) and 1080ngL(-1), respectively in effluent wastewaters. Removal rates (RE%) for the target compounds in each WWTPs were calculated. RE% for parabens were almost 100%, whereas for BP4 values where in the range 5-91%. The half-life time (t1/2), hydraulic retention time (HRT), and annual mass load (ML) for each facility was estimated. Results indicated that there was no clear influence of HRT on the RE% of BP4. MLs for BP4 were in the range 0.9-110.1kgy(-1), with the highest values in the most populated areas. Finally, a risk assessment, estimated in terms of hazard quotients (HQs), was carried out for aquatic biota. HQs for the target compounds in effluent wastewaters indicated a negligible effect, whereas for some influent wastewaters' HQs pointed out that some species are at risk. PMID:26905612

  2. Application and validation of chemometrics-assisted spectrophotometry and liquid chromatography for the simultaneous determination of six-component pharmaceuticals.

    PubMed

    El-Gindy, Alaa; Emara, Samy; Mostafa, Ahmed

    2006-05-01

    Three methods are developed for the simultaneous determination of theophylline anhydrous (TH), guaiphenesin (GP), diphenhydramine hydrochloride (DP), methylparaben (MP), propylparaben (PP) and sodium benzoate (BZ) in pharmaceutical syrup. The chromatographic method depends on a high performance liquid chromatographic separation on a reversed-phase C(18) column at ambient temperature with mobile phase consisting of 25 mM KH2PO4, pH 3.2-acetonitrile (60:40, v/v). Quantitation was achieved with UV detection at 222 nm based on peak area. The other two chemometric methods applied were partial least squares (PLS-1) and principal component regression (PCR). These approaches were successfully applied to quantify the six components in the studied mixture using information included in the UV absorption spectra of appropriate solutions in the wavelength range of 220-270 nm with Deltalambda=0.4 nm. The calibration PLS-1 and PCR models were evaluated by internal validation (prediction of compounds in its own designed training set of calibration), by cross-validation (obtaining statistical parameters that show the efficiency for a calibration fit model) and by external validation over synthetic and pharmaceutical preparation. The results of PLS-1 and PCR methods were compared with the HPLC method and a good agreement was found. PMID:16414231

  3. Evaluating food additives as antifungal agents against Monilinia fructicola in vitro and in hydroxypropyl methylcellulose-lipid composite edible coatings for plums.

    PubMed

    Karaca, Hakan; Pérez-Gago, María B; Taberner, Verònica; Palou, Lluís

    2014-06-01

    Common food preservative agents were evaluated in in vitro tests for their antifungal activity against Monilinia fructicola, the most economically important pathogen causing postharvest disease of stone fruits. Radial mycelial growth was measured in Petri dishes of PDA amended with three different concentrations of the agents (0.01-0.2%, v/v) after 7 days of incubation at 25 °C. Thirteen out of fifteen agents tested completely inhibited the radial growth of the fungus at various concentrations. Among them, ammonium carbonate, ammonium bicarbonate and sodium bicarbonate were the most effective while sodium acetate and sodium formate were the least effective. The effective agents and concentrations were tested as ingredients of hydroxypropyl methylcellulose (HPMC)-lipid edible coatings against brown rot disease on plums previously inoculated with M. fructicola (curative activity). 'Friar' and 'Larry Ann' plums were inoculated with the pathogen, coated with stable edible coatings about 24h later, and incubated at 20 °C and 90% RH. Disease incidence (%) and severity (lesion diameter) were determined after 4, 6, and 8 days of incubation and the 'area under the disease progress stairs' (AUDPS) was calculated. Coatings containing bicarbonates and parabens significantly reduced brown rot incidence in plums, but potassium sorbate, used at 1.0% in the coating formulation, was the most effective agent with a reduction rate of 28.6%. All the tested coatings reduced disease severity to some extent, but coatings containing 0.1% sodium methylparaben or sodium ethylparaben or 0.2% ammonium carbonate or ammonium bicarbonate were superior to the rest, with reduction rates of 45-50%. Overall, the results showed that most of the agents tested in this study had significant antimicrobial activity against M. fructicola and the application of selected antifungal edible coatings is a promising alternative for the control of postharvest brown rot in plums. PMID:24742996

  4. Analysis of multi-class preservatives in leave-on and rinse-off cosmetics by matrix solid-phase dispersion.

    PubMed

    Sanchez-Prado, Lucia; Alvarez-Rivera, Gerardo; Lamas, J Pablo; Lores, Marta; Garcia-Jares, Carmen; Llompart, Maria

    2011-12-01

    Matrix solid-phase extraction has been successfully applied for the determination of multi-class preservatives in a wide variety of cosmetic samples including rinse-off and leave-on products. After extraction, derivatization with acetic anhydride, and gas chromatography-mass spectrometry analysis were performed. Optimization studies were done on real non-spiked and spiked leave-on and rinse-off cosmetic samples. The selection of the most suitable extraction conditions was made using statistical tools such as ANOVA, as well as factorial experimental designs. The final optimized conditions were common for both groups of cosmetics and included the dispersion of the sample with Florisil (1:4), and the elution of the MSPD column with 5 mL of hexane/acetone (1:1). After derivatization, the extract was analyzed without any further clean-up or concentration step. Accuracy, precision, linearity and detection limits were evaluated to assess the performance of the proposed method. The recovery studies on leave-on and rinse-off cosmetics gave satisfactory values (>78% for all analytes in all the samples) with an average relative standard deviation value of 4.2%. The quantification limits were well below those set by the international cosmetic regulations, making this multi-component analytical method suitable for routine control. The analysis of a broad range of cosmetics including body milk, moisturizing creams, anti-stretch marks creams, hand creams, deodorant, shampoos, liquid soaps, makeup, sun milk, hand soaps, among others, demonstrated the high use of most of the target preservatives, especially butylated hydroxytoluene, methylparaben, propylparaben, and butylparaben. PMID:21947013

  5. Chronic toxicity of parabens and their chlorinated by-products in Ceriodaphnia dubia.

    PubMed

    Terasaki, Masanori; Abe, Ryoko; Makino, Masakazu; Tatarazako, Norihisa

    2015-01-01

    The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC50 values for mortality, offspring number, and first brood production ranged between 0.30-3.1, 0.047-12, and 1.3-6.3 mg L(-1) , respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg L(-1) and from 1.2 to 19 mg L(-1) , respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl2 BnP) elicited a significant decrease in offspring numbers even at their lowest concentration tested; the NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg L(-1) for MP, BnP, and Cl2 BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent response; their NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0

  6. Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring.

    PubMed

    Rager, Julia E; Strynar, Mark J; Liang, Shuang; McMahen, Rebecca L; Richard, Ann M; Grulke, Christopher M; Wambaugh, John F; Isaacs, Kristin K; Judson, Richard; Williams, Antony J; Sobus, Jon R

    2016-03-01

    ), Triclocarban, Diethyl phthalate (DEP), Propylparaben, Methylparaben, Tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and Nicotine. This study demonstrates a novel suspect screening methodology to prioritize chemicals of interest for subsequent targeted analysis. The methods described here rely on strategic integration of available public resources and should be considered in future non-targeted and suspect screening assessments of environmental and biological media. PMID:26812473

  7. Formation of organic nanoparticles from volatile microemulsions.

    PubMed

    Margulis-Goshen, Katrin; Netivi, Hadas Donio; Major, Dan T; Gradzielski, Michael; Raviv, Uri; Magdassi, Shlomo

    2010-02-15

    A method for preparation of nanoparticles of poorly water-soluble organic materials is presented. By this method, an oil-in-water microemulsion containing a volatile solvent with dissolved model material, propylparaben, undergoes solvent evaporation and conversion into nanoparticles by spray drying. The resulting powder can be easily dispersed in water to give a clear, stable dispersion of nanoparticles with a high loading of propylparaben. By filtration of this dispersion it was found that more than 95wt.% of the dispersed propylparaben is in particles of less than 450nm. X-ray diffraction revealed that propylparaben is present as nanocrystals of 40-70nm. After dispersion of the powder in water, formation of large crystals rapidly occurs. Addition of polyvinylpyrrolidone (PVP) prevented crystal growth during dispersion of the powder in water. The inhibition of propylparaben crystal growth by PVP was studied by molecular dynamic simulations that addressed the binding of PVP to the propylparaben crystal. A comparison was made between PVP and polyvinylalcohol, which did not display crystal inhibition properties. PMID:19919861

  8. Non-traditional plasticization of polymeric films.

    PubMed

    Wu, C; McGinity, J W

    1999-01-15

    The objective of this study was to investigate the influence of methylparaben, ibuprofen, chlorpheniramine maleate and theophylline on the thermal and mechanical properties of polymeric films of Eudragit RS 30 D. The effects of methylparaben and ibuprofen in the film coating on the rate of drug release from Eudragit RS 30 D coated beads were also studied. The physical and mechanical properties of the cast films and coated beads were investigated using thermal analysis, tensile testing, X-ray diffraction analysis and dissolution testing. The results demonstrated that the glass transition temperature of the Eudragit RS 30 D decreased with increasing levels of methylparaben, ibuprofen and chlorpheniramine maleate in the film. Theophylline exerted no influence on the thermal properties of the polymer. The higher levels of the ibuprofen and methylparaben incorporated into the film resulted in a decrease in the tensile strength of the film. The decrease in Young's modulus of Eudragit RS 30 D coated beads was attributed to an increase in the flexibility of the polymeric films when the level of methylparaben or ibuprofen in the polymeric dispersion was increased. The dissolution data demonstrated that the rate of release of the ibuprofen from coated beads was decreased by increasing the amount of ibuprofen and methylparaben in the polymeric film coating. PMID:10205601

  9. Antifungal agents against Aspergillus niger for rearing rice leaffolder larvae (Lepidoptera: Pyralidae) on artificial diet.

    PubMed

    Su, Jianya; Wang, Ye-Cheng; Zhang, Shu-Kun; Ren, Xiu-Bei

    2014-06-01

    Mold contamination is an important issue in insect mass rearing. Frequently used antifungal agents such as sorbic acid and methylparaben have negative impact on many lepidopteran larvae, which might be one of the reasons for the difficulty in rearing rice leaffolder, Cnaphalocrocis medinalis (Güenée). In this study, 19 antifungal agents, including 7 food preservatives, 6 antifungal drugs, and 6 agricultural fungicides, were screened for their inhibitory activities on Aspergillus niger in diets. The results demonstrated that most of the tested chemicals are unsuitable as mold inhibitors in the diets of the rice leaffolder, and the rice leaffolder neonate is sensitive to sorbic acid and methylparaben. These two mold inhibitors at commonly used concentrations were shown to impact the survival of rice leaffolder larvae fed on artificial diets. Among the tested mold inhibitors, natamycin was the safest for the rice leaffolder larvae. Much higher larva survival was observed for the larvae fed on diets containing natamycin as an antifungal agent (59 and 72% at 200 and 400 ppm, respectively). Two agricultural fungicides, tebuconazole and azoxystrobin, are also potent as mold inhibitors when used in insect diets. The mixed use of natamycin and sorbic acid, or methylparaben, and the mixed use of sorbic acid and azoxystrobin resulted in significantly higher larva survival than sorbic acid + methylparaben. Natamycin + azoxystrobin and sorbic acid + tebuconazole resulted in larva survival similar to that of sorbic acid + methylparaben. The ternary combination of natamycin, sorbic acid, and methylparaben was the best combination for the rearing of rice leaffolder. PMID:25026669

  10. Essential oils and herbal extracts as antimicrobial agents in cosmetic emulsion.

    PubMed

    Herman, Anna; Herman, Andrzej Przemysław; Domagalska, Beata Wanda; Młynarczyk, Andrzej

    2013-06-01

    The cosmetic industry adapts to the needs of consumers seeking to limit the use of preservatives and develop of preservative-free or self-preserving cosmetics, where preservatives are replaced by raw materials of plant origin. The aim of study was a comparison of the antimicrobial activity of extracts (Matricaria chamomilla, Aloe vera, Calendula officinalis) and essential oils (Lavandulla officinallis, Melaleuca alternifolia, Cinnamomum zeylanicum) with methylparaben. Extracts (2.5 %), essential oils (2.5 %) and methylparaben (0.4 %) were tested against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, Candida albicans ATCC 14053. Essentials oils showed higher inhibitory activity against tested microorganism strain than extracts and methylparaben. Depending on tested microorganism strain, all tested extracts and essential oils show antimicrobial activity 0.8-1.7 and 1-3.5 times stronger than methylparaben, respectively. This shows that tested extracts and essential oils could replace use of methylparaben, at the same time giving a guarantee of microbiological purity of the cosmetic under its use and storage. PMID:24426114

  11. Photodegradation of parabens by Fe(III)-citrate complexes at circumneutral pH: matrix effect and reaction mechanism.

    PubMed

    Feng, Xiaonan; Chen, Yong; Fang, Yuan; Wang, Xiaoyue; Wang, Zongping; Tao, Tao; Zuo, Yuegang

    2014-02-15

    The photodegradation of four parabens including methyl-, ethyl-, propyl-, and butyl-paraben in the presence of Fe(III)-citrate complexes under simulated sunlight was investigated. The degradation of parabens increased with decreasing pH within the range of 5.0-8.0 at the Fe(III)-to-citrate ratio of 10:150 (μM). The addition of low-molecular-weight carboxylic acids showed different effects on the photodegradation of methylparaben. The low-photoreactive carboxylic acids inhibited the photodegradation of methylparaben in the order of formic acid>succinic acid>acetic acid>malonic acid. In contrast, oxalic acid enhanced the photodegradation and exhibited appreciable synergistic effect with Fe(III)-citrate at concentration higher than 500 μM. Up to 99.0% of substrate was degraded after 30 min at pH6.0 in the Fe(III)-citrate-oxalate system. The various fractions of fulvic acid inhibited the photodegradation of methylparaben. The inhibition increased with increasing nominal molecular weight of fractionated fulvic acid. Moreover, the photodegradation of methylparaben was inhibited in natural waters in the order of Liangzi Lakemethylparaben were identified by GC-MS analyses and the degradation pathway was proposed. PMID:24291138

  12. 76 FR 16290 - Tolerances for Residues of New Animal Drugs in Food; 2-Acetylamino-5-Nitrothiazole; Buquinolate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ...) and as Sec. 556.550 (40 FR 13802 at 13956). 12. Salicylic acid (Sec. 556.590). In 2005, FDA...; Prednisolone; Prednisone; Progesterone; Propylparaben; and Salicylic Acid AGENCY: Food and Drug Administration... (44 FR 40888, July 13, 1979), but did not amend part 556 to remove the associated tolerances....

  13. Action of methyl-, propyl- and butylparaben on GPR30 gene and protein expression, cAMP levels and activation of ERK1/2 and PI3K/Akt signaling pathways in MCF-7 breast cancer cells and MCF-10A non-transformed breast epithelial cells.

    PubMed

    Wróbel, Anna Maria; Gregoraszczuk, Ewa Łucja

    2015-10-14

    In the present study, we examined cAMP levels and activation of the MAPK/ERK1/2 and PI3K/Akt signaling pathways in response to the actions of parabens on GPR30 in MCF-7 and MCF-10A cells. Cells were exposed to methyl-, propyl- or butylparaben at a concentration of 20nM; 17-β-estradiol (10nM) was used as a positive control. 17β-estradiol and all tested parabens increased GPR30 gene and protein expression in MCF-7 and MCF-10A cells. No parabens affected cAMP levels in either cell line, with the exception of propylparaben in MCF-10A cells. 17β-estradiol, propylparaben, and butylparaben increased phosphorylation of ERK1/2 in MCF-7 cells, whereas 17β-estradiol, methyl- and butylparaben, but not propylparaben, increased phosphorylation of ERK1/2 in MCF-10A cells. Akt activation was noted only in MCF-7 cells and only with propylparaben treatment. Collectively, the data presented here point to a nongenomic mechanism of action of parabens in activation GPR30 in both cancer and non-cancer breast cell lines through βγ dimer-mediated activation of the ERK1/2 pathway, but not the cAMP/PKA pathway. Moreover, among investigated parabens, propylparaben appears to inhibit apoptosis in cancer cells through activation of Akt kinases, confirming conclusions suggested by our previously published data. Nevertheless, continuing research on the carcinogenic action of parabens is warranted. PMID:26253279

  14. Transplacental passage of antimicrobial paraben preservatives.

    PubMed

    Towers, Craig V; Terry, Paul D; Lewis, David; Howard, Bobby; Chambers, Wesley; Armistead, Casey; Weitz, Beth; Porter, Stephanie; Borman, Christopher J; Kennedy, Rebekah C M; Chen, Jiangang

    2015-01-01

    Parabens are widely used preservatives suspected of being endocrine disruptors, with implications for human growth and development. The most common paraben found in consumer products is methylparaben. To date, no study has examined whether these substances cross the human placenta. A total of 100 study subjects (50 mother-child pairs) were enrolled at two medical institutions, serving primarily African-American and Caucasian women, respectively. A maternal blood sample was drawn on admission and a paired cord blood sample was obtained at delivery. Of the 50 mothers, 47 (94%) showed methylparaben in their blood (mean level 20.41 ng/l), and 47 in cords bloods (mean level 36.54 ng/l). There were 45 mother-child pairs where methylparaben was found in both samples. Of these, the fetal level was higher than the maternal level in 23 (51%). For butylparaben, only 4 mothers (8%) showed detectable levels (mean 40.54 ng/l), whereas 8 cord blood samples (16%) were positive (mean 32.5 ng/l). African-American mothers and infants showed higher prevalence of detectable levels (P=0.017). Methylparaben and butylparaben demonstrate transplacental passage. Additional studies are needed to examine potential differences in exposure by geography and demographics, what products are used by pregnant women that contain these preservatives, as well as any potential long-term effects in the growth and development of exposed children. PMID:25944699

  15. Thonningiiflavanonol A and thonningiiflavanonol B, two novel flavonoids, and other constituents of Ficus thonningii Blume (Moraceae).

    PubMed

    Ango, Patrick Y; Kapche, Deccaux W F G; Fotso, Ghislain W; Fozing, Christian D; Yeboah, Elizabeth M O; Mapitse, Renameditswe; Demirtas, Ibrahim; Ngadjui, Bonaventure T; Yeboah, Samuel O

    2016-03-01

    A phytochemical study of Ficus thonningii has led to the isolation of two previously unreported compounds, thonningiiflavanonol A and thonningiiflavanonol B together with 16 known compounds: shuterin, naringenin, syringic acid, p-hydroxybenzoic acid, genistein, 5,7,3',4',5'-pentahydroxyflavanone, luteolin, methylparaben, aromadendrin, garbanzol, dihydroquercetin, 5,7,3'-trihydroxyflavanone, β-sitosterol, sitosterolglucoside, lupeol acetate, and taraxerol. Their structures were elucidated on the basis of spectroscopic data. The new compounds and extracts displayed potent antioxidant activity. PMID:26959540

  16. Novel Stability-Indicating RP-HPLC Method for the Simultaneous Estimation of Clindamycin Phosphate and Adapalene along with Preservatives in Topical Gel Formulations.

    PubMed

    Modi, Prakash B; Shah, Nehal J

    2014-12-01

    A novel stability-indicating RP-HPLC method was developed for the simultaneous estimation of clindamycin phosphate (hydrophilic), adapalene (hydro-phobic), phenoxyethanol, and methylparaben in topical gel formulations. Optimum chromatographic separation among the analytes and stress-induced degradants peaks was achieved on the XBridge C18 (50 × 4.6 mm, 3.5 µm) column using a mobile phase consisting of a variable mixture of pH 2.50 ammonium hydrogen phosphate buffer, acetonitrile, and tetrahydrofuran with gradient elution. Detection was performed at 210 nm for phenoxyethanol, methylparaben, and clindamycin phosphate and 321 nm for adapalene. The method was optimized with a unique diluent selection for the extraction of clindamycin phosphate and adapalene from the gel matrix. The developed method was validated for method precision, specificity, LOD and LOQ, linearity, accuracy, robustness, and solution stability as per ICH guidelines. The proposed method can be employed for the quantification of clindamycin phosphate, adapalene, phenoxyethanol, and methylparaben in commercial topical gel formulations. PMID:26171325

  17. Novel Stability-Indicating RP-HPLC Method for the Simultaneous Estimation of Clindamycin Phosphate and Adapalene along with Preservatives in Topical Gel Formulations

    PubMed Central

    Modi, Prakash B.; Shah, Nehal J.

    2014-01-01

    Abstract A novel stability-indicating RP-HPLC method was developed for the simultaneous estimation of clindamycin phosphate (hydrophilic), adapalene (hydro-phobic), phenoxyethanol, and methylparaben in topical gel formulations. Optimum chromatographic separation among the analytes and stress-induced degradants peaks was achieved on the XBridge C18 (50 × 4.6 mm, 3.5 µm) column using a mobile phase consisting of a variable mixture of pH 2.50 ammonium hydrogen phosphate buffer, acetonitrile, and tetrahydrofuran with gradient elution. Detection was performed at 210 nm for phenoxyethanol, methylparaben, and clindamycin phosphate and 321 nm for adapalene. The method was optimized with a unique diluent selection for the extraction of clindamycin phosphate and adapalene from the gel matrix. The developed method was validated for method precision, specificity, LOD and LOQ, linearity, accuracy, robustness, and solution stability as per ICH guidelines. The proposed method can be employed for the quantification of clindamycin phosphate, adapalene, phenoxyethanol, and methylparaben in commercial topical gel formulations. PMID:26171325

  18. Effect of Ternary Solutes on the Evolution of Structure and Gel Formation in Amphiphilic Copolymer Solutions

    NASA Astrophysics Data System (ADS)

    Meznarich, Norman Anthony Kang

    Aqueous solutions of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) amphiphilic triblock copolymers (commercially known as Pluronic surfactants) undergo reversible and temperature-dependent micellization and arrangement into cubic ordered lattices known as "micelle gels". The macroscopic behavior of the ordering is a transition from a liquid to a gel. While the phase behavior and gel structure of pure Pluronic surfactant solutions have been well studied, less is known about the effects of added ternary solutes. In this dissertation, a comprehensive investigation into the effects of the added pharmaceutical methylparaben on solutions of F127 ranging from 10 to 30 wt% was conducted in order to better understand the behavior of F127 in multicomponent pharmaceutical formulations. The viscoelastic properties of F127 gel formation were studied using rheometry, where heating rates of 0.1, 1, and 10 degrees C/min were also used to probe the kinetics of the gel transition. In solutions containing methylparaben, F127 gelation occurred at up to 15 degrees C lower temperatures and was accelerated by a factor of three to four. Small angle x-ray scattering (SAXS) was used to characterize the structure of the ordered domains, and how they were affected by the presence of dissolved pharmaceuticals. It was found that ordered domain formation changed from heterogeneous nucleation and growth to possible homogeneous nucleation and growth. A roughly 2% reduction in the cubic lattice parameter was also observed for solutions containing methylparaben. Differential scanning calorimetry (DSC) experiments were performed on a series of different Pluronic surfactants in order to characterize the micellization behavior as a function of PPO center block length and PEO/PPO ratio. Added methylparaben suppressed the micellization endotherm, the degree of suppression depending linearly on the amount of added methylparaben, as well as the length of the PPO center block and PEO

  19. Release of antimicrobial actives from microcapsules by the action of axillary bacteria.

    PubMed

    Kromidas, L; Perrier, E; Flanagan, J; Rivero, R; Bonnet, I

    2006-04-01

    We describe the use of unique microcapsules that may be degraded by the actions of bacteria. These microcapsules are approximately 35 mum in diameter, are composed of natural protein, and may be filled with a variety of actives. We describe the use of antimicrobial actives such as farnesol and methylparaben to demonstrate that their release by the degradative actions of axillary bacteria such as Corynebacterium minutissimum, C. urealyticum, and Staphylococcus epidermidis leads to their demise. These microcapsules may be used in consumer products such as deodorants and antiperpirants that may, under actual use conditions, control malodor. PMID:18492144

  20. Actions of methyl-, propyl- and butylparaben on estrogen receptor-α and -β and the progesterone receptor in MCF-7 cancer cells and non-cancerous MCF-10A cells.

    PubMed

    Wróbel, Anna Maria; Gregoraszczuk, Ewa Łucja

    2014-11-01

    Numerous studies have shown that widely used parabens possess estrogenic properties. In the present study, we examined the effects of methyl-, propyl- and butylparaben on the mRNA and protein expression of estrogen receptor (ER)-α (ESR1) and -β (ESR2) and the progesterone receptor (PGR). Human MCF-7 breast cancer cells and MCF-10A non-transformed breast epithelial cells were exposed to parabens at a concentration of 20nM; 17β-estradiol at a concentration of 10nM, was used as a positive control. Both propyl- and butylparaben stimulated PGR mRNA expression in MCF-7 cells, whereas methyl- and propylparaben PGR protein expression. In MCF-10A cells, butyl- and propylparaben increased only PGR mRNA expression. All parabens increased ESR1 gene and protein expression in MCF-7 and with the exception of butylparaben in MCF-10A cells. All parabens significantly increased ESR2 mRNA and protein expression in MCF-7 cells, but in MCF-10A cells only ESR2 protein expression. In summary, by virtue of their stimulatory action on the expression of ESR1, ESR2 and PGR in cancer cells, parabens can be viewed as potential contributors to breast cancer progression. Extension, the actions of these parabens on the expression of ERs and PGR in non-cancerous cells point to possible actions on breast cancer initiation. PMID:25128701

  1. Inhibition of hepatic microsomal carboxylesterase activity by paraoxon.

    PubMed

    Castle, M C

    1988-01-01

    A large number of therapeutic agents are esters of carboxylic acids and are thus substrates for microsomal carboxylesterase enzymes. These studies characterized the effects of the organophosphate compound, paraoxon, on the hydrolysis of several drug esters (procaine, chloramphenicol succinate, prednisolone succinate, lidocaine, procainamide and methylparaben) by microsomal preparations from guinea-pigs. These investigations demonstrate that carboxylesterase activity toward several drug esters is present in liver, lung and kidney. The liver is by far the major site of hydrolysis of these ester compounds. Since no hydrolysis was observed with the two amide esters, the hydrolysis of carboxylesters and amide esters appears to be mediated by different enzymes in the guinea-pig. At the substrate concentrations studied, the hydrolysis of methylparaben followed zero-order kinetics. When added to isolated microsomal preparations, paraoxon produced a dose-dependent inhibition of hydrolysis of all substrates. Administration of paraoxon to guinea-pigs prior to isolation of microsomes did not produce consistent effects with any substrate. Inhibition of ester hydrolysis was observed with some pretreatments, while either no change or increased hydrolysis was observed with other pretreatment regimens. PMID:3245748

  2. Personal care product preservatives: risk assessment and mixture toxicities with an industrial wastewater.

    PubMed

    Carbajo, Jose B; Perdigón-Melón, Jose A; Petre, Alice L; Rosal, Roberto; Letón, Pedro; García-Calvo, Eloy

    2015-04-01

    The aquatic toxicity of eight preservatives frequently used in personal care products (PCPs) (iodopropynyl butylcarbamate, bronopol, diazolidinyl urea, benzalkonium chloride, zinc pyrithione, propylparaben, triclosan and a mixture of methylchloroisothiazolinone and methylisothiazolinone) was assessed by means of two different approaches: a battery of bioassays composed of single species tests of bacteria (Vibrio fischeri and Pseudomonas putida) and protozoa (Tetrahymena thermophila), and a whole biological community resazurin-based assay using activated sludge. The tested preservatives showed considerable toxicity in the studied bioassays, but with a marked difference in potency. In fact, all biocides except propylparaben and diazolidinyl urea had EC50 values lower than 1 mg L(-1) in at least one assay. Risk quotients for zinc pyrithione, benzalkonium chloride, iodopropynyl butylcarbamate and triclosan as well as the mixture of the studied preservatives exceeded 1, indicating a potential risk for the process performance and efficiency of municipal sewage treatment plants (STPs). These four single biocides explained more than 95% of the preservative mixture risk in all bioassays. Each individual preservative was also tested in combination with an industrial wastewater (IWW) from a cosmetics manufacturing facility. The toxicity assessment was performed on binary mixtures (preservative + IWW) and carried out using the median-effect principle, which is a special case of the concept of Concentration Addition (CA). Almost 70% of all experiments resulted in EC50 values within a factor of 2 of the values predicted by the median-effect principle (CI values between 0.5 and 2). The rest of the mixtures whose toxicity was mispredicted by CA were assessed with the alternative concept of Independent Action (IA), which showed higher predictive power for the biological community assay. Therefore, the concept used to accurately predict the toxicity of mixtures of a preservative

  3. Antibacterial Effects of Cinnamon: From Farm to Food, Cosmetic and Pharmaceutical Industries

    PubMed Central

    Nabavi, Seyed Fazel; Di Lorenzo, Arianna; Izadi, Morteza; Sobarzo-Sánchez, Eduardo; Daglia, Maria; Nabavi, Seyed Mohammad

    2015-01-01

    Herbs and spices have been used since ancient times, because of their antimicrobial properties increasing the safety and shelf life of food products by acting against foodborne pathogens and spoilage bacteria. Plants have historically been used in traditional medicine as sources of natural antimicrobial substances for the treatment of infectious disease. Therefore, much attention has been paid to medicinal plants as a source of alternative antimicrobial strategies. Moreover, due to the growing demand for preservative-free cosmetics, herbal extracts with antimicrobial activity have recently been used in the cosmetic industry to reduce the risk of allergies connected to the presence of methylparabens. Some species belonging to the genus Cinnamomum, commonly used as spices, contain many antibacterial compounds. This paper reviews the literature published over the last five years regarding the antibacterial effects of cinnamon. In addition, a brief summary of the history, traditional uses, phytochemical constituents, and clinical impact of cinnamon is provided. PMID:26378575

  4. Physicochemical characterization of emulgel formulated with SepineoP 600, SepineoSE 68 and cosolvent mixtures.

    PubMed

    Khalil, Enam A; Majid, Samia A; Suaifan, Ghadeer A R Y; Al-Akayleh, Faisal T; Sallam, Al-Sayed A

    2016-08-01

    The combined properties of SepineoP 600 (S600), a self-gelling dispersion and SepineoSE 68 (M68), a natural liquid crystal forming surfactant, were utilized in the development of emulgel base for topical application. The emulgels were prepared in water alone or combined with propylene glycol (PG), polyethylene glycol 400 (PEG400) and glycerol (G) as cosolvents. Emulgels were characterized for their optical and flow behavior. Two model drugs: caffeine (CF) and methylparaben (MP) were used in the evaluation of drug permeation across the stratum corneum (SC). The results showed that emulgel prepared using 70% PG:water (1:1) and 30% S600 has the best flow behavior compared to other cosolvents. Also the permeability coefficient of CF was found to be higher than that of MP and the addition of 3% M68 improved the physical stability of the emulgel, but it did not affect the drug diffusion profile. PMID:25757641

  5. Antibacterial Effects of Cinnamon: From Farm to Food, Cosmetic and Pharmaceutical Industries.

    PubMed

    Nabavi, Seyed Fazel; Di Lorenzo, Arianna; Izadi, Morteza; Sobarzo-Sánchez, Eduardo; Daglia, Maria; Nabavi, Seyed Mohammad

    2015-09-01

    Herbs and spices have been used since ancient times, because of their antimicrobial properties increasing the safety and shelf life of food products by acting against foodborne pathogens and spoilage bacteria. Plants have historically been used in traditional medicine as sources of natural antimicrobial substances for the treatment of infectious disease. Therefore, much attention has been paid to medicinal plants as a source of alternative antimicrobial strategies. Moreover, due to the growing demand for preservative-free cosmetics, herbal extracts with antimicrobial activity have recently been used in the cosmetic industry to reduce the risk of allergies connected to the presence of methylparabens. Some species belonging to the genus Cinnamomum, commonly used as spices, contain many antibacterial compounds. This paper reviews the literature published over the last five years regarding the antibacterial effects of cinnamon. In addition, a brief summary of the history, traditional uses, phytochemical constituents, and clinical impact of cinnamon is provided. PMID:26378575

  6. Stability of succinylcholine chloride injection at ambient temperature and 4 deg C in polypropylene syringes.

    PubMed

    Storms, Meredith L; Stewart, James T; Warren, Flynn W

    2003-01-01

    The stability of 20-mg/mL succinylcholine chloride injection in 12-mL polypropylene syringes stored at ambient temperature and 4 deg C for up to 90 days was investigated. Concentration levels of succinylcholine chloride injection were determined at 0, 1, 4, 7, 15, 30, 45, 60, and 90 days after preparation of the syringes by means of a high-performance liquid chromatographic stability-indicating assay. Methylparaben, which was added as a preservative, did not interfere with the assay. The loss in potency was less than 10% after 45 days of storage at 25 deg C and less than 1% after 90 days of storage at 4 deg C. The pH of succinylcholine chloride injection did not change appreciably during the 90-day study period. PMID:23979509

  7. Biocides in the Yangtze River of China: spatiotemporal distribution, mass load and risk assessment.

    PubMed

    Liu, Wang-Rong; Zhao, Jian-Liang; Liu, You-Sheng; Chen, Zhi-Feng; Yang, Yuan-Yuan; Zhang, Qian-Qian; Ying, Guang-Guo

    2015-05-01

    Nineteen biocides were investigated in the Yangtze River to understand their spatiotemporal distribution, mass loads and ecological risks. Fourteen biocides were detected, with the highest concentrations up to 166 ng/L for DEET in surface water, and 54.3 ng/g dry weight (dw) for triclocarban in sediment. The dominant biocides were DEET and methylparaben, with their detection frequencies of 100% in both phases. An estimate of 152 t/y of 14 biocides was carried by the Yangtze River to the East China Sea. The distribution of biocides in the aquatic environments was significantly correlated to Gross Domestic Product (GDP), total phosphorus (TP) and total nitrogen (TN), suggesting dominant input sources from domestic wastewater of the cities along the river. Risk assessment showed high ecological risks posed by carbendazim in both phases and by triclosan in sediment. Therefore, proper measures should be taken to reduce the input of biocides into the river systems. PMID:25697474

  8. UHPLC-MS/MS method for the determination of bisphenol A and its chlorinated derivatives, bisphenol S, parabens, and benzophenones in human urine samples.

    PubMed

    Vela-Soria, F; Ballesteros, O; Zafra-Gómez, A; Ballesteros, L; Navalón, A

    2014-06-01

    In the present work, a new method based on a sample treatment by dispersive liquid-liquid microextraction (DLLME) for the extraction of six bisphenols (bisphenol A, bisphenol S, and monochloro-, dichloro-, trichloro-, and tetrachlorobisphenol A), four parabens (methyl-, ethyl-, propyl-, and butylparaben), and six benzophenones (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8, and 4-hydroxybenzophenone) in human urine samples, followed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is validated. An enzymatic treatment allows determining the total content of the target EDCs. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-(13)C6, benzophenone-d10, and bisphenol A-d16 were used as surrogates. Limits of quantification ranging from 0.1 to 0.6 ng mL(-1) and interday variabilities (evaluated as relative standard deviations) from 2.0 to 13.8% were obtained. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 94 to 106%. A good linearity, for concentrations up to 300 ng mL(-1) for parabens and 40 ng mL(-1) for benzophenones and bisphenols, was also obtained. The method was satisfactorily applied for the determination of target compounds in human urine samples from 20 randomly selected individuals. PMID:24710638

  9. Luminescent homo- and hetero-metallic hybrid molecular materials constructed by covalent grafting

    NASA Astrophysics Data System (ADS)

    Wang, F. F.; Yan, B.

    2013-01-01

    In this paper, 3-(triethoxysilyl)-propyl isocyanate (abbreviated as TESPIC) was modified by ethylparaben (EPB) to produce corresponding organic-inorganic monomers (EPB-TESPIC) with two components equipped with covalent bonds, which not only can coordinate to RE ions (Tb3+ and Eu3+) but also act as a sol-gel precursor. Luminescent hybrid materials consisting of terbium-europium complex, covalently bonded to silica-based network, have been obtained in situ via a sol-gel approach. Proton nuclear magnetic resonance spectroscopy (1HNMR) and Fourier transform infrared spectroscopy (FT-IR) were applied to characterize the structure of EPB-TESPIC. UV-visible, phosphorescence, and luminescence spectra were obtained to characterize the photophysical properties of the obtained hybrid material. Through co-hydrolysis and polycondensation, Tb3+ and Eu3+ can be introduced into the same organic-inorganic hybrid monomer, forming Si-O backbones. The experimental results show that the strong luminescence of rare-earth ions substantiates the optimum energy match and effective intramolecular energy transfer between the triplet state energy of coordination complex and the emissive energy level of the rare-earth ions. The hybrid material systems are expected to have potential applications in photophysical sensors.

  10. Sequential injection chromatographic determination of ambroxol hydrochloride and doxycycline in pharmaceutical preparations.

    PubMed

    Satínský, Dalibor; Santos, Lucia M L Dos; Sklenárová, Hana; Solich, Petr; Montenegro, M Conceição B S M; Araújo, Alberto N

    2005-12-15

    A new separation method based on a novel reversed-phase sequential injection chromatography (SIC) technique was used for simultaneous determination of ambroxol hydrochloride and doxycycline in pharmaceutical preparations in this contribution. The coupling of short monolith with SIA system results in an implementation of separation step to until no-separation low-pressure method. A Chromolith((R)) Flash RP-18e, 25-4.6mm column (Merck, Germany) and a FIAlab((R)) 3000 system (USA) with a six-port selection valve and 5ml syringe were used for sequential injection chromatographic separations in our study. The mobile phase used was acetonitrile-water (20:90, v/v), pH 2.5 adjusted with 98% phosphoric acid, flow rate 0.48mlmin(-1), UV detection was at 213nm. The validation parameters have shown good results: linearity of determination for both compounds including internal standard (ethylparaben) >0.999; repeatability of determination (R.S.D.) in the range 0.5-5.4% at three different concentration levels, detection limits in the range 0.5-2.0mugml(-1), and recovery from the pharmaceutical preparation in the range 99.3-99.9%. The chromatographic resolution between peak compounds was >5.0 and analysis time was <9min under the optimal conditions. The method was found to be applicable for routine analysis of the active compounds ambroxol hydrochloride and doxycycline in various pharmaceutical preparations. PMID:18970307

  11. Ultra-performance liquid chromatography MS/MS method for the determination of parabens in compost from sewage sludge: comparison of the efficiency of two extraction techniques.

    PubMed

    Benítez-Villalba, Julio César; Zafra-Gómez, Alberto; Dorival-García, Noemí; Camino-Sánchez, Francisco Javier; Cantarero, Samuel; Vílchez, José Luis

    2013-08-01

    The efficiency of two extraction techniques--ultrasound-assisted extraction and pressurized liquid extraction--are compared and evaluated in the determination of parabens in compost samples. The extraction parameters for each technique were accurately optimized. The selected compounds were detected and quantified using ultra-performance LC MS/MS, operating in negative ESI and in SRM mode. The analytes were separated in less than 5 min. Ethylparaben (ring-(13)C6 labeled) was used as an internal standard. Two selective, sensitive, and accurate analytical methods were developed and validated. The LODs of the methods ranged from 3 to 7 ng/g and the LOQs from 10 to 23 ng/g, while inter- and intraday variability was under 6% in all cases. The methods were validated separately by using matrix-matched calibration and recovery assays with spiked samples. Recovery rates ranged from 94.0 to 105.0%. Compost samples were taken from different composting plants. Although the statistical comparison demonstrated no statistically significant differences between the two extraction techniques, the method based on pressurized liquid extraction was more sensitive than the ultrasound extraction based method. PMID:23868707

  12. Determination of selected parabens, benzophenones, triclosan and triclocarban in agricultural soils after and before treatment with compost from sewage sludge: A lixiviation study.

    PubMed

    Camino-Sánchez, F J; Zafra-Gómez, A; Dorival-García, N; Juárez-Jiménez, B; Vílchez, J L

    2016-04-01

    An accurate and sensitive method for the determination of selected EDCs in soil and compost from wastewater treatment plants is developed and validated. Five parabens, six benzophenone-UV filters and the antibacterials triclosan and triclocarban were selected as target analytes. The parameters for ultrasound-assisted extraction were thoroughly optimized. After extraction, the analytes were detected and quantified using ultra-high performance liquid chromatography tandem mass spectrometry. Ethylparaben (ring-(13)C6 labelled) and deuterated benzophenone (BP-d10) were used as internal standards. The method was validated using matrix-matched calibration and recovery assays with spiked samples. The limits of detection ranged from 0.03 to 0.40 ng g(-1) and the limits of quantification from 0.1 to 1.0 ng g(-1), while precision in terms of relative standard deviation was between 9% and 21%. Recovery rates ranged from 83% to 107%. The validated method was applied for the study of the behavior of the selected compounds in agricultural soils treated and un-treated with compost from WWTP. A lixiviation study was developed in both agricultural soil and treated soil and first order kinetic models of their disappearance at different depths are proposed. The application of organic composts in the soil leads to an increase of the disappearance rate of the studied compounds. The lixiviation study also shows the risk of pollution of groundwater aquifers after disposal or waste of these EDCs in agricultural soils is not high. PMID:26838425

  13. Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in malaria vaccine studies

    PubMed Central

    2014-01-01

    Background When rhesus monkeys (Macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. However, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. Thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines. To better assess malaria vaccines in rhesus, a method to challenge large numbers of monkeys by mosquito bite was developed. Methods Several species and strains of mosquitoes were tested for their ability to produce Plasmodium knowlesi sporozoites. Donor monkey parasitaemia effects on oocyst and sporozoite numbers and mosquito mortality were documented. Methylparaben added to mosquito feed was tested to improve mosquito survival. To determine the number of bites needed to infect a monkey, animals were exposed to various numbers of P. knowlesi-infected mosquitoes. Finally, P. knowlesi-infected mosquitoes were used to challenge 17 monkeys in a malaria vaccine trial, and the effect of number of infectious bites on monkey parasitaemia was documented. Results Anopheles dirus, Anopheles crascens, and Anopheles dirus X (a cross between the two species) produced large numbers of P. knowlesi sporozoites. Mosquito survival to day 14, when sporozoites fill the salivary glands, averaged only 32% when donor monkeys had a parasitaemia above 2%. However, when donor monkey parasitaemia was below 2%, mosquitoes survived twice as well and contained ample sporozoites in their salivary glands. Adding methylparaben to sugar solutions did not improve survival of infected mosquitoes. Plasmodium knowlesi was very infectious, with all monkeys developing blood stage infections if one or more infected mosquitoes successfully fed. There was also a dose-response, with monkeys that received higher numbers of infected mosquito bites developing malaria sooner. Conclusions Anopheles dirus, An. crascens and a

  14. Oestrogenic activity of benzylparaben.

    PubMed

    Darbre, P D; Byford, J R; Shaw, L E; Hall, S; Coldham, N G; Pope, G S; Sauer, M J

    2003-01-01

    Previous work has demonstrated that the alkyl esters of p-hydroxybenzoic acid (parabens) possess oestrogenic activity, which increases with length of alkyl chain from methylparaben to n-butylparaben and with branching in the alkyl chain from n-butylparaben to isobutylparaben. This study reports on the oestrogenic activity of benzylparaben in a variety of assays in vitro and in vivo. Benzylparaben was able to displace [(3)H]oestradiol from cytosolic oestrogen receptor (ER) of MCF7 human breast cancer cells by 22% at 1000-fold molar excess, by 40% at 10,000-fold molar excess, by 57% at 100 000-fold molar excess and by 100% at 1,000,000-fold molar excess. It was able to increase expression of a stably transfected oestrogen responsive reporter gene (ERE-CAT) in MCF7 cells after 24 h at 10(-5)M/10(-4)M and after 7 days at 10(-6)M/10(-5)M/10(-4)M. Proliferation of MCF7 cells could be increased by 10(-6)M/10(-5)M benzylparaben and this could be inhibited by 10(-7)M pure anti-oestrogen ICI 182,780, indicating that growth effects were ER mediated. Further evidence for ER-mediation was provided from the ability of benzylparaben to increase the growth of a second oestrogen-dependent human breast cancer cell line ZR-75-1, but not the oestrogen-insensitive MDA-MB-231 cell line. When tested in the presence of 10(-10)M 17beta-oestradiol, benzylparaben gave no antagonist response on the growth of either MCF7 or ZR-75-1 cells. Finally, benzylparaben could increase uterine weight in the immature mouse following topical application of three daily doses of 33 mg to dorsal skin. These results demonstrate that the oestrogenicity of methylparaben can be increased by the addition of an aryl group as well as by lengthening or branching the alkyl grouping. PMID:12518336

  15. Thermodynamic investigation of the interaction between cyclodextrins and preservatives - Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations.

    PubMed

    Holm, René; Olesen, Niels Erik; Alexandersen, Signe Dalgaard; Dahlgaard, Birgitte N; Westh, Peter; Mu, Huiling

    2016-05-25

    Preservatives are inactivated when added to conserve aqueous cyclodextrin (CD) formulations due to complex formation between CDs and the preservative. To maintain the desired conservation effect the preservative needs to be added in apparent surplus to account for this inactivation. The purpose of the present work was to establish a mathematical model, which defines this surplus based upon knowledge of stability constants and the minimal concentration of preservation to inhibit bacterial growth. The stability constants of benzoic acid, methyl- and propyl-paraben with different frequently used βCDs were determined by isothermal titration calorimetry. Based upon this knowledge mathematical models were constructed to account for the equilibrium systems and to calculate the required concentration of the preservations, which was evaluated experimentally based upon the USP/Ph. Eur./JP monograph. The mathematical calculations were able to predict the needed concentration of preservation in the presence of CDs; it clearly demonstrated the usefulness of including all underlying chemical equilibria in a mathematical model, such that the formulation design can be based on quantitative arguments. PMID:26391874

  16. A simple and rapid 3D view method for selective and sensitive determination of paclitaxel in micro volume rat plasma by LC-diode array UV and its application to a pharmacokinetic study.

    PubMed

    Kumar, Sekar Vasantha; Srinath, Selladurai; Saha, Ranendra N

    2012-03-01

    A simple, highly repeatable and reproducible method for the estimation of Paclitaxel (TAX) in micro volume amounts of rat plasma is successfully developed and validated. The extraction procedure using 800 µL of ice-cold acetonitrile is very simple and economical with high sensitivity. The rectangular ratiograms and purity curve demonstrate the selectivity of the method. The validation and stability results show that propylparaben (PP) is a suitable internal standard (resolution 7.70 ± 0.15 min) for the estimation of TAX in micro volume rat plasma. TAX and PP are separated by isocratic reversed-phase high-performance liquid chromatography with diode array UV method with a retention time of 8.0 ± 0.25 and 5.3 ± 0.15 min, respectively, with a total run time of 10 min. The system suitability results show that the method has good reproducibility. The stability of TAX is well studied in rat plasma, and the % RSD of all stability studies of TAX are well within the acceptable range of ± 20 % at the lower limit of quantitation (LLOQ) and ± 15% at all quality control levels. The limit of detection (LOD) and LLOQ of the method are 5 and 10 ng/mL, respectively. This rapid method is successfully used to study the i.v pharmacokinetic of TAX at 10 mg/kg in wistar rats, and drug concentration is detected up to 24 h. PMID:22337803

  17. Contributions of Abiotic and Biotic Processes to the Aerobic Removal of Phenolic Endocrine-Disrupting Chemicals in a Simulated Estuarine Aquatic Environment.

    PubMed

    Yang, Lihua; Cheng, Qiao; Tam, Nora Fy; Lin, Li; Su, Weiqi; Luan, Tiangang

    2016-04-19

    The contributions of abiotic and biotic processes in an estuarine aquatic environment to the removal of four phenolic endocrine-disrupting chemicals (EDCs) were evaluated through simulated batch reactors containing water-only or water-sediment collected from an estuary in South China. More than 90% of the free forms of all four spiked EDCs were removed from these reactors at the end of 28 days under aerobic conditions, with the half-life of 17α-ethynylestradiol (EE2) longer than those of propylparaben (PP), nonylphenol (NP) and 17β-estradiol (E2). The interaction with dissolved oxygen contributed to NP removal and was enhanced by aeration. The PP and E2 removal was positively influenced by adsorption on suspended particles initially, whereas abiotic transformation by estuarine-dissolved matter contributed to their complete removal. Biotic processes, including degradation by active aquatic microorganisms, had significant effects on the removal of EE2. Sedimentary inorganic and organic matter posed a positive effect only when EE2 biodegradation was inhibited. Estrone (E1), the oxidizing product of E2, was detected, proving that E2 was removed by the naturally occurring oxidizers in the estuarine water matrixes. These results revealed that the estuarine aquatic environment was effective in removing free EDCs, and the contributions of abiotic and biotic processes to their removal were compound specific. PMID:26984110

  18. Screening of preservatives by HPLC-PDA-ESI/MS: A focus on both allowed and recently forbidden compounds in the new EU cosmetics regulation.

    PubMed

    Lecce, Raffaele; Regazzoni, Luca; Mustazza, Carlo; Incarnato, Giampaolo; Porrà, Rita; Panusa, Alessia

    2016-06-01

    Commission regulation (EU) No 358/2014 amending the new regulation (EC) No 1223/2009 on cosmetics has prohibited the use of isopropyl-, isobutyl-, phenyl-, benzyl- and pentylparaben. Furthermore, Commission regulation (EU) No 1004/2014 has lowered the maximum permitted concentration of butyl- and propylparaben in cosmetics and it has also banned them in leave-on products designed for application on the nappy area of children under three years of age. A HPLC-PDA-ESI/MS method has been developed herein for the detection of seventeen preservatives, both the most utilised and the recently forbidden by the new EU regulations. The separation of these compounds, including benzoic acid and its derivatives in a 1.10 - 3.04 log Pow range, has been performed with a gradient elution on a Symmetry(®) C18 column (250×4.6mm i.d., particle size 5μm) with water and acetonitrile (0.1% formic acid) as mobile phase. Quantification has been carried out by HPLC-PDA. The method has been validated and successfully applied to the analysis of a large number of cosmetics with different functions like rinse-off and leave-on, or composition like skin, hair, face and oral products. PMID:27055177

  19. Effect-directed identification of endocrine disruptors in plastic baby teethers.

    PubMed

    Berger, Elisabeth; Potouridis, Theodoros; Haeger, Astrid; Püttmann, Wilhelm; Wagner, Martin

    2015-11-01

    Concerns have been raised regarding the human health effects of endocrine disrupting chemicals (EDCs), many of which are associated with and leaching from plastics. As infants are particularly vulnerable to EDCs, we have investigated whether plastic teethers for babies represent a relevant source of exposure. Applying effect-directed analysis, we use bioassays to screen teethers, toys used to soothe a baby's teething ache, for endocrine activity and chemical analysis to identify the causative compounds. We detected significant endocrine activity in two of 10 plastic teethers. Those samples leached estrogenic and/or antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast Antiandrogen Screen. After sample fractionation, gas chromatography-mass spectrometry non-target screening revealed that methyl-, ethyl- and propylparaben were responsible for the observed estrogenic and antiandrogenic activity in one product. The second product is likely to contain at least six different antiandrogenic compounds that remain so far unidentified. This study demonstrates that plastic teethers can be a source of infant exposure to well-established and unknown EDCs. Because of their limited value to the product, but potential toxicity, manufacturers should critically revisit the use of parabens in plastic teethers and further toys. Moreover, plastic teethers might leach EDCs that escape routine analysis and, thus, toxicological evaluation. The resulting uncertainty in product safety poses a problem to consumers, producers and regulators that remain to be resolved. PMID:25988240

  20. Multi-class method for biomonitoring of hair samples using gas chromatography-mass spectrometry.

    PubMed

    Martín, Julia; Möder, Monika; Gaudl, Alexander; Alonso, Esteban; Reemtsma, Thorsten

    2015-11-01

    Currently, non-invasive biomonitoring of human exposure to organic pollutants bases upon the analysis mainly of urine and human breast milk. While mostly persistent organic pollutants are the center of interest, the aim of our study was to develop a method for the determination of different chemical classes of emerging pollutants (organophosphorus flame retardants, plastic additives such as phthalates, bisphenol A, insecticides, antimicrobials, preservatives and musk fragrances) in hair by gas chromatography-mass spectrometry. The preferred sample preparation included hydrolysis of the hair with trifluoroacetic acid in methanol followed by a liquid-liquid extraction using hexane/ethyl acetate. The validated method is characterized by recoveries higher than 77 % for most analytes, relative standard deviations below 16 % and limits of detection between 2 pg mg(-1) (HHCB) and 292 pg mg(-1) (propylparaben) using 50 mg of dry hair. After respective blank corrections, bis-(2-ethylhexyl)phthalate (DEHP) and the musk fragrance HHCB were the predominant compounds determined in all hair samples at concentrations between 32 and 59 ng mg(-1) and 0.8-13 ng mg(-1), respectively. The bactericide triclosan and the insect repellent N,N-diethyl-3-methylbenzamide (DEET) were detected in selected hair samples at 2 and 0.8 ng mg(-1), respectively. PMID:26427497

  1. A new method for rapid determination of indole-3-carbinol and its condensation products in nutraceuticals using core-shell column chromatography method.

    PubMed

    Fibigr, Jakub; Šatínský, Dalibor; Havlíková, Lucie; Solich, Petr

    2016-02-20

    Indole-3-carbinol is a natural glucosinolate known for prevention of human breast, prostate and other types of cancer and it started to be used in commercial preparations, as food supplements. However no analytical method has been proposed for quality control of nutraceuticals with this substance yet. In this paper a new high-performance liquid chromatography (HPLC) method using core-shell column for separation of indole-3-carbinol and its condensation/degradation products was developed and used for the quantitative determination of indole-3-carbinol in nutraceuticals. Separation of indole-3-carbinol, its condensation/degradation products and internal standard ethylparaben was performed on the core-shell column Kinetex 5μ XB-C18 100A (100×4.6mm), particle size 5.0μm, with mobile phase acetonitrile/water according to the gradient program at a flow rate of 1.25mLmin(-1) and at temperature 50°C. The detection wavelength was set at 270nm. Under the optimal chromatographic conditions good linearity of determination was achieved. Available commercial samples of nutraceuticals were extracted with 100% methanol using ultrasound bath. A 5-μL sample volume of the supernatant was directly injected into the HPLC system. The developed method provided rapid and accurate tool for quality control of nutraceuticals based on cruciferous vegetable extracts with indole-3-carbinol content. The presented study showed that the declared content of indole-3-carbinol significantly varied in the different nutraceuticals available on the market. Two analyzed preparations showed the presence of condensation/degradation products of indole-3-carbinol which were not officially declared by the manufacturer. Moreover, further two analyzed nutraceutical preparations showed absolutely no content of declared amount of indole-3-carbinol. PMID:26795880

  2. Assessment of the sensitizing potency of preservatives with chance of skin contact by the loose-fit coculture-based sensitization assay (LCSA).

    PubMed

    Sonnenburg, Anna; Schreiner, Maximilian; Stahlmann, Ralf

    2015-12-01

    Parabens, methylisothiazolinone (MI) and its derivative methylchloroisothiazolinone (MCI), are commonly used as preservatives in personal care products. They can cause hypersensitivity reactions of the human skin. We have tested a set of nine parabens, MI alone and in combination with MCI in the loose-fit coculture-based sensitization assay (LCSA). The coculture of primary human keratinocytes and allogenic dendritic cell-related cells (DC-rc) in this assay emulates the in vivo situation of the human skin. Sensitization potency of the test substances was assessed by flow cytometric analysis of the DC-rc maturation marker CD86. Determination of the concentration required to cause a half-maximal increase in CD86-expression (EC50sens) allowed a quantitative evaluation. The cytotoxicity of test substances as indicator for irritative potency was measured by 7-AAD (7-amino-actinomycin D) staining. Parabens exhibited weak (methyl-, ethyl-, propyl- and isopropylparaben) or strong (butyl-, isobutyl-, pentyl- and benzylparaben) effects, whereas phenylparaben was found to be a moderate sensitizer. Sensitization potencies of parabens correlated with side chain length. Due to a pronounced cytotoxicity, we could not estimate an EC50sens value for MI, whereas MI/MCI was classified as sensitizer and also showed cytotoxic effects. Parabens showed no (methyl- and ethylparaben) or weak irritative potencies (propyl-, isopropyl-, butyl-, isobutyl-, phenyl- and benzylparaben), only pentylparaben was rated to be irritative. Overall, we were able to demonstrate and compare the sensitizing potencies of parabens in this in vitro test. Furthermore, we showed an irritative potency for most of the preservatives. The data further support the usefulness of the LCSA for comparison of the sensitizing potencies of xenobiotics. PMID:25395006

  3. Urinary concentrations of parabens in Chinese young adults: implications for human exposure.

    PubMed

    Ma, Wan-Li; Wang, Lei; Guo, Ying; Liu, Li-Yan; Qi, Hong; Zhu, Ning-Zheng; Gao, Chong-Jing; Li, Yi-Fan; Kannan, Kurunthachalam

    2013-10-01

    Parabens are widely used as preservatives in foods, cosmetics, and pharmaceuticals. However, recent studies have indicated that high and systemic exposure to parabens can be harmful to human health. Although a few studies have reported urinary paraben levels in western countries, studies on paraben exposure in the Chinese population are limited. China is currently a major producer of parabens in the world. In this study, 109 urine samples collected from Chinese young adults (approximately 20 years old) were analyzed for five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens) by high-performance liquid chromatography-tandem mass spectrometry. Methyl-, propyl-, and ethyl-parabens were the three major paraben analogues found in all (100%) samples. The concentration of the sum of the five parabens ranged from 0.82 to 728 ng/mL with a geometric mean value of 17.4 ng/mL. Urinary concentration of parabens was 2-fold greater in females than in males. Based on the measured urinary concentrations, daily intake of parabens by the Chinese young adults was estimated and compared with those reported for United States adults. The estimated daily intakes (EDIurine) of parabens were 18.4 and 40.8 μg/kg bw/day for Chinese males and females, respectively, values that were lower than those reported for United States adults (74.7 μg/kg bw/day). Based on the reported concentrations of parabens in foods from China and the United States, the contribution of dietary intake to EDIurine was estimated to be 5.5, 2.6, and 0.42% for Chinese males, Chinese females, and United States adults, respectively, which indicates the significance of nondietary sources of parabens to human exposures. PMID:23744051

  4. Aggregate exposure approaches for parabens in personal care products: a case assessment for children between 0 and 3 years old.

    PubMed

    Gosens, Ilse; Delmaar, Christiaan J E; Ter Burg, Wouter; de Heer, Cees; Schuur, A Gerlienke

    2014-01-01

    In the risk assessment of chemical substances, aggregation of exposure to a substance from different sources via different pathways is not common practice. Focusing the exposure assessment on a substance from a single source can lead to a significant underestimation of the risk. To gain more insight on how to perform an aggregate exposure assessment, we applied a deterministic (tier 1) and a person-oriented probabilistic approach (tier 2) for exposure to the four most common parabens through personal care products in children between 0 and 3 years old. Following a deterministic approach, a worst-case exposure estimate is calculated for methyl-, ethyl-, propyl- and butylparaben. As an illustration for risk assessment, Margins of Exposure (MoE) are calculated. These are 991 and 4966 for methyl- and ethylparaben, and 8 and 10 for propyl- and butylparaben, respectively. In tier 2, more detailed information on product use has been obtained from a small survey on product use of consumers. A probabilistic exposure assessment is performed to estimate the variability and uncertainty of exposure in a population. Results show that the internal exposure for each paraben is below the level determined in tier 1. However, for propyl- and butylparaben, the percentile of the population with an exposure probability above the assumed "safe" MoE of 100, is 13% and 7%, respectively. In conclusion, a tier 1 approach can be performed using simple equations and default point estimates, and serves as a starting point for exposure and risk assessment. If refinement is warranted, the more data demanding person-oriented probabilistic approach should be used. This probabilistic approach results in a more realistic exposure estimate, including the uncertainty, and allows determining the main drivers of exposure. Furthermore, it allows to estimate the percentage of the population for which the exposure is likely to be above a specific value. PMID:23801276

  5. A multiclass method for the analysis of endocrine disrupting chemicals in human urine samples. Sample treatment by dispersive liquid-liquid microextraction.

    PubMed

    Vela-Soria, F; Ballesteros, O; Zafra-Gómez, A; Ballesteros, L; Navalón, A

    2014-11-01

    The population is continuously exposed to endocrine disrupting chemicals (EDCs). This has influenced an increase in diseases and syndromes that are more frequent nowadays. Therefore, it is necessary to develop new analytical procedures to evaluate the exposure with the ultimate objective of establishing, in an accurate way, relationships between EDCs and harmful health effects. In the present work, a new method based on a sample treatment by dispersive liquid-liquid microextraction (DLLME) for the extraction of six parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl and butylparaben), six benzophenones (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8 and 4-hydroxybenzophenone) and two bisphenols (bisphenol A and bisphenol S) in human urine samples, followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis is proposed. An enzymatic treatment allows determining the total content of the target EDCs. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-(13)C6 and bisphenol A-d16 were used as surrogates. Found limits of quantification ranging from 0.2 to 0.5 ng mL(-1) and inter-day variability (evaluated as relative standard deviation) ranging from 2.0% to 14.9%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 94% to 105%. A good linearity, for concentrations up to 300 ng mL(-1) for parabens and 40 ng mL(-1) for benzophenones and bisphenols, respectively, was obtained. The method was satisfactorily applied for the determination of target compounds in human urine samples from 20 randomly selected individuals. PMID:25127586

  6. Simplified matrix solid phase dispersion procedure for the determination of parabens and benzophenone-ultraviolet filters in human placental tissue samples.

    PubMed

    Vela-Soria, F; Rodríguez, I; Ballesteros, O; Zafra-Gómez, A; Ballesteros, L; Cela, R; Navalón, A

    2014-12-01

    In recent decades, the industrial development has resulted in the appearance of a large amount of new chemicals that are able to produce disorders in the human endocrine system. These substances, so-called endocrine disrupting chemicals (EDCs), include many families of compounds, such as parabens and benzophenone-UV filters. Taking into account the demonstrated biological activity of these compounds, it is necessary to develop new analytical procedures to assess the exposure in order to establish, in an accurate way, relationships between EDCs and harmful health effects in population. In the present work, a new method based on a simplified sample treatment by matrix solid phase dispersion (MSPD) followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, is validated for the determination of four parabens (methyl-, ethyl-, propyl- and butylparaben) and six benzophenone-UV filters (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8 and 4-hydroxybenzophenone) in human placental tissue samples. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-13C6 and benzophenone-d10 were used as surrogates. The found limits of quantification ranged from 0.2 to 0.4 ng g(-1) and inter-day variability (evaluated as relative standard deviation) ranged from 5.4% to 12.8%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 96% to 104%. The method was satisfactorily applied for the determination of compounds in human placental tissue samples collected at the moment of delivery from 10 randomly selected women. PMID:25456585

  7. New method for the determination of parabens and bisphenol A in human milk samples using ultrasound-assisted extraction and clean-up with dispersive sorbents prior to UHPLC-MS/MS analysis.

    PubMed

    Rodríguez-Gómez, R; Dorival-García, N; Zafra-Gómez, A; Camino-Sánchez, F J; Ballesteros, O; Navalón, A

    2015-06-15

    A sensitive and accurate analytical method for the determination of methyl-, ethyl-, propyl- and butylparaben and bisphenol A in human milk samples has been developed and validated. The combination of ultrasound-assisted extraction (UAE) and a simplified and rapid clean-up technique that uses sorbent materials has been successfully applied for the preparation of samples prior to ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The analytes were extracted from freeze-dried human milk samples using acetonitrile and ultrasonic radiation (three 15-min cycles at 70% amplitude), and further cleaned-up with C18 sorbents. The most influential parameters affecting the UAE method and the clean-up steps were optimized using design of experiments. Negative electrospray ionization (ESI) in the selected reaction monitoring (SRM) mode was used for MS detection. The use of two reactions for each compound allowed simultaneous quantification and identification in one run. The analytes were separated in less than 10min. Deuterium-labeled ethylparaben-d5 (EPB-d5) and deuterium-labeled bisphenol A-d16 (BPA-d16) were used as surrogates. The limits of quantification ranged from 0.4 to 0.7ngmL(-1), while inter- and intra-day variability was under 11.1% in all cases. In the absence of certified reference materials, recovery assays with spiked samples using matrix-matched calibration were used to validate the method. Recovery rates ranged from 93.8% to 112.2%. The proposed method was satisfactorily applied for the determination of four selected parabens and bisphenol A in human milk samples obtained from nursing mothers living in the province of Granada (Spain). PMID:25942557

  8. Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.

    PubMed

    Cai, Zheng; Song, Xiangrong; Sun, Feng; Yang, Zhaoxiang; Hou, Shixiang; Liu, Zhongqiu

    2011-12-01

    Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin. PMID:21879392

  9. A new treatment by dispersive liquid-liquid microextraction for the determination of parabens in human serum samples.

    PubMed

    Vela-Soria, F; Ballesteros, O; Rodríguez, I; Zafra-Gómez, A; Ballesteros, L; Cela, R; Navalón, A

    2013-09-01

    Alkyl esters of p-hydroxybenzoic acid (parabens) are a family of compounds that have been in use since the 1920s as preservatives in cosmetic formulations, with one of the lowest rates of skin problems reported in dermatological patients. However, in the last few years, many scientific publications have demonstrated that parabens are weak endocrine disruptors, meaning that they can interfere with the function of endogenous hormones, increasing the risk of breast cancer. In the present work, a new sample treatment method is introduced based on dispersive liquid-liquid microextraction for the extraction of the most commonly used parabens (methyl-, ethyl-, propyl-, and butylparaben) from human serum samples followed by separation and quantification using ultrahigh performance liquid chromatography-tandem mass spectrometry. The method involves an enzymatic treatment to quantify the total content of parabens. The extraction parameters (solvent and disperser solvent, extractant and dispersant volume, pH of the sample, salt addition, and extraction time) were accurately optimized using multivariate optimization strategies. Ethylparaben ring (13)C6-labeled was used as surrogate. Limits of quantification ranging from 0.2 to 0.7 ng mL(-1) and an interday variability (evaluated as relative standard deviations) from 3.8 to 11.9 % were obtained. The method was validated using matrix-matched calibration standard and a spike recovery assay. Recovery rates for spiked samples ranged from 96 to 106 %, and a good linearity up to concentrations of 100 ng mL(-1) was obtained. The method was satisfactorily applied for the determination of target compounds in human serum samples. PMID:23857141

  10. Determination of parabens and endocrine-disrupting alkylphenols in soil by gas chromatography-mass spectrometry following matrix solid-phase dispersion or in-column microwave-assisted extraction: a comparative study.

    PubMed

    Pérez, R A; Albero, B; Miguel, E; Sánchez-Brunete, C

    2012-03-01

    Two rapid methods were evaluated for the simultaneous extraction of seven parabens and two alkylphenols from soil based on matrix solid-phase dispersion (MSPD) and microwave-assisted extraction (MAE). Soil extracts were derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide and analyzed by gas chromatography with mass spectrometry. Extraction and clean-up of samples were carried out by both methods in a single step. A glass sample holder, inside the microwave cell, was used in MAE to allow the simultaneous extraction and clean-up of samples and shorten the MAE procedure. The detection limits achieved by MSPD were lower than those obtained by MAE because the presence of matrix interferences increased with this extraction method. The extraction yields obtained by MSPD and MAE for three different types of soils were compared. Both procedures showed good recoveries and sensitivity for the determination of parabens and alkylphenols in two of the soils assayed, however, only MSPD yielded good recoveries with the other soil. Finally, MSPD was applied to the analysis of soils collected in different sites of Spain. In most of the samples analyzed, methylparaben and butylparaben were detected at levels ranging from 1.21 to 8.04 ng g(-1) dry weight and 0.48 to 1.02 ng g(-1) dry weight, respectively. PMID:21792551

  11. Overcoming the nail barrier: A systematic investigation of ungual chemical penetration enhancement.

    PubMed

    Brown, M B; Khengar, R H; Turner, R B; Forbes, B; Traynor, M J; Evans, C R G; Jones, S A

    2009-03-31

    This study investigated the in vitro nail permeability of penetrants of varying lipophilicity-caffeine (CF, logP -0.07), methylparaben (MP, logP 1.96) and terbinafine (TBF, logP 3.3) and the effect of 2 novel penetration enhancers (PEs), thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) on their permeation. Studies were conducted using full thickness human nail clippings and ChubTur((R)) diffusion cells and penetrants were applied as saturated solutions. The rank order of steady-state penetrant flux through nails without PE application (MP>CF>TBF) suggested a greater sensitivity to penetrant molecular weight rather than logP. TA increased the flux of CF and MP approximately 4- and approximately 2-fold, respectively, whilst urea H(2)O(2) proved ineffective at enhancing permeability. The sequential application of TA followed by urea H(2)O(2) increased TBF and CF flux ( approximately 19- and approximately 4-fold, respectively) but reversing the application order of the PEs was only mildly effective at increasing just MP flux ( approximately 2-fold). Both nail PEs are likely to function via disruption of keratin disulphide bonds and the associated formation of pores that provide more 'open' drug transport channels. Effects of the PEs were penetrant specific, but the use of a reducing agent (TA) followed by an oxidising agent (urea H(2)O(2)) dramatically improved human nail penetration. PMID:19071202

  12. Stability of an extemporaneously compounded levothyroxine sodium oral liquid.

    PubMed

    Boulton, D W; Fawcett, J P; Woods, D J

    1996-05-15

    The stability of levothyroxine sodium in oral liquid dosage forms compounded from commercially available tablets was studied. Levothyroxine sodium oral liquids (25 micrograms/mL) were prepared from tablets and from powder with and without methylparaben preservative and transferred to amber, high-density polyethylene bottles. Five bottles of each tablet-based formulation were stored at 2-8 degrees C, 23-27 degrees C, and 38-42 degrees C, and five bottles of each powder-based formulation were stored at 38-42 degrees C. On days 3, 8, 14, 22, 31, 61, and 90, samples were taken from each bottle and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. There was significant degradation of levothyroxine sodium in all the formulations. However, the tablet-based formulation without preservative stored at 4 degrees C retained at least 90% of its initial concentration for eight days after compounding. Degradation occurred faster in the tablet-based formulation with preservative. None of the formulations retained > or = 90% initial potency by day 14. An extemporaneous oral liquid formulation of levothyroxine sodium 25 micrograms/mL compounded from crushed tablets was stable for eight days when stored in amber bottles at 4 degrees C. PMID:8734676

  13. Gene expression responses for detecting sublethal effects of xenobiotics and whole effluents on a Xenopus laevis embryo assay.

    PubMed

    San Segundo, Laura; Martini, Federica; Pablos, M Victoria

    2013-09-01

    In the present study, the authors investigated the effects of bisphenol A, chlorpyrifos, methylparaben, and 2 effluent samples from wastewater treatment plants located in the province of Madrid, Spain, on the messenger RNA expression of specific genes involved in early development (ESR1, pax6, bmp4, and myf5) and a gene involved in the general stress response (hsp70) during Xenopus laevis embryo development. Gene expression was analyzed after 4 h, 24 h, and 96 h of exposure by semiquantitative reverse-transcriptase-polymerase chain reaction. Concentration ranges of the compounds and dilutions for the samples were selected to cause morphological alterations in embryos after 96 h of exposure. Transcript levels of ESR1, pax6, and hsp70 were differentially altered at early developmental stages with patterns specific to the contaminant and the exposure time. However, further studies are needed to establish transcript levels of specific genes as biomarkers of sublethal effects in an environmental risk-assessment framework. Besides, studies including more generic responses, such as genes encoding antioxidant enzymes, together with genes related to embryonic development have to be developed to look for a battery of mechanistic endpoints for the evaluation of chemical exposure at the molecular level in a first-tier assessment. PMID:23637088

  14. Changes in the Metabolome in Response to Low-Dose Exposure to Environmental Chemicals Used in Personal Care Products during Different Windows of Susceptibility

    PubMed Central

    Chen, Jia; Belpoggi, Fiorella; Manservisi, Fabiana; Sánchez-Guijo, Alberto; Wudy, Stefan A.; Teitelbaum, Susan L.

    2016-01-01

    The consequences of ubiquitous exposure to environmental chemicals remain poorly defined. Non-targeted metabolomic profiling is an emerging method to identify biomarkers of the physiological response to such exposures. We investigated the effect of three commonly used ingredients in personal care products, diethyl phthalate (DEP), methylparaben (MPB) and triclosan (TCS), on the blood metabolome of female Sprague-Dawley rats. Animals were treated with low levels of these chemicals comparable to human exposures during prepubertal and pubertal windows as well as chronically from birth to adulthood. Non-targeted metabolomic profiling revealed that most of the variation in the metabolites was associated with developmental stage. The low-dose exposure to DEP, MPB and TCS had a relatively small, but detectable impact on the metabolome. Multiple metabolites that were affected by chemical exposure belonged to the same biochemical pathways including phenol sulfonation and metabolism of pyruvate, lyso-plasmalogens, unsaturated fatty acids and serotonin. Changes in phenol sulfonation and pyruvate metabolism were most pronounced in rats exposed to DEP during the prepubertal period. Our metabolomics analysis demonstrates that human level exposure to personal care product ingredients has detectable effects on the rat metabolome. We highlight specific pathways such as sulfonation that warrant further study. PMID:27467775

  15. Changes in the Metabolome in Response to Low-Dose Exposure to Environmental Chemicals Used in Personal Care Products during Different Windows of Susceptibility.

    PubMed

    Houten, Sander M; Chen, Jia; Belpoggi, Fiorella; Manservisi, Fabiana; Sánchez-Guijo, Alberto; Wudy, Stefan A; Teitelbaum, Susan L

    2016-01-01

    The consequences of ubiquitous exposure to environmental chemicals remain poorly defined. Non-targeted metabolomic profiling is an emerging method to identify biomarkers of the physiological response to such exposures. We investigated the effect of three commonly used ingredients in personal care products, diethyl phthalate (DEP), methylparaben (MPB) and triclosan (TCS), on the blood metabolome of female Sprague-Dawley rats. Animals were treated with low levels of these chemicals comparable to human exposures during prepubertal and pubertal windows as well as chronically from birth to adulthood. Non-targeted metabolomic profiling revealed that most of the variation in the metabolites was associated with developmental stage. The low-dose exposure to DEP, MPB and TCS had a relatively small, but detectable impact on the metabolome. Multiple metabolites that were affected by chemical exposure belonged to the same biochemical pathways including phenol sulfonation and metabolism of pyruvate, lyso-plasmalogens, unsaturated fatty acids and serotonin. Changes in phenol sulfonation and pyruvate metabolism were most pronounced in rats exposed to DEP during the prepubertal period. Our metabolomics analysis demonstrates that human level exposure to personal care product ingredients has detectable effects on the rat metabolome. We highlight specific pathways such as sulfonation that warrant further study. PMID:27467775

  16. Occurrence, fate and risk assessment of parabens and their chlorinated derivatives in an advanced wastewater treatment plant.

    PubMed

    Li, Wenhui; Shi, Yali; Gao, Lihong; Liu, Jiemin; Cai, Yaqi

    2015-12-30

    In the present study, parabens, p-hydroxybenzoic acid (PHBA) and chlorinated derivatives, were simultaneously determined in wastewater and sludge samples along the whole process in an advanced wastewater treatment plant (WWTP). Nine target compounds were detected in this WWTP, and methylparaben and PHBA were the dominant compounds in these samples. It is noteworthy that octylparaben with longer chain was firstly detected in this work. Mass balance results showed that 91.8% of the initial parabens mass loading was lost mainly due to degradation, while the contribution of sorption and output of primary and excess sludge was much less (7.5%), indicating that biodegradation played a significant role in the removal of parabens during the conventional treatment process. Specifically, parabens were mainly degraded in the anaerobic tank, and PHBA could be effectively removed at high rates after the advanced treatment. However, both biodegradation and adsorption accounted for minor contribution to the removal of chlorinated parabens during conventional treatment process, and they were only scantly removed by conventional treatment (33.9-40.7%) and partially removed by advanced treatment (59.2-82.8%). Risk assessment indicated that parabens and their chlorinated derivatives in second and tertiary effluent are not likely to produce biological effects on aquatic ecosystems. PMID:26151382

  17. Occurrence of and dietary exposure to parabens in foodstuffs from the United States.

    PubMed

    Liao, Chunyang; Liu, Fang; Kannan, Kurunthachalam

    2013-04-16

    Parabens are esters of p-hydroxybenzoic acid and are widely used as preservatives in cosmetics, pharmaceuticals, foodstuffs, including beverages. Information on the occurrence of parabens in foodstuffs and dietary exposure of humans to these chemicals is not available. In this study, food samples (n = 267) collected from Albany, New York, United States, were grouped into eight categories, namely, beverages, dairy products, fats and oils, fish and shellfish, grains, meat, fruits, and vegetables, and analyzed for five parabens by high-performance liquid chromatography-tandem mass spectrometry. The majority (>90%) of food samples contained measurable concentrations of parabens, and the total concentrations (Σparabens; sum of five parabens) ranged from below the limit of quantitation to 409 ng/g fresh weight (mean: 9.67 ng/g; median: 0.92 ng/g). Methyl-, ethyl-, and propyl-parabens were the predominant compounds, accounting for ∼90% of the total concentrations. Butyl- and benzyl-parabens were less frequently detected. There were no significant differences in paraben concentrations among the eight food categories, including the canned foods. On the basis of the concentrations measured and per capita daily ingestion rates of foods, we estimated the daily intake (EDI; ng/kg of body weight (bw)/day)) of parabens through food ingestion. The EDI values of total parabens (calculated from the mean concentrations measured and the mean daily ingestion rates of food items) were 940, 879, 470, 273, and 307 ng/kg bw/day for infants, toddlers, children, teenagers, and adults, respectively. To our knowledge, this is the first study to report the occurrence of parabens in foodstuffs. PMID:23506043

  18. Quaternary polymethacrylate-magnesium aluminum silicate films: Water uptake kinetics and film permeability.

    PubMed

    Rongthong, Thitiphorn; Sungthongjeen, Srisagul; Siepmann, Florence; Siepmann, Juergen; Pongjanyakul, Thaned

    2015-07-25

    The aim of this study was to investigate the impact of the addition of different amounts of magnesium aluminum silicate (MAS) to polymeric films based on quaternary polymethacrylates (QPMs, here Eudragit RS and RL). MAS contains negatively charged SiO(-) groups, while QPM contains positively charged quaternary ammonium groups. The basic idea is to be able to provide desired water and drug permeability by simply varying the amount of added MAS. Thin, free films of varying composition were prepared by casting and exposed to 0.1M HCl and pH 6.8 phosphate buffer. The water uptake kinetics and water vapor permeability of the systems were determined gravimetrically. The transport of propranolol HCl, acetaminophen, methyl-, ethyl- and propylparaben across thin films was studied using side-by-side diffusion cells. A numerical solution of Fick's second law of diffusion was applied to determine the apparent compound diffusion coefficients, partition coefficients between the bulk fluids and the films as well as the apparent film permeability for these compounds. The addition of MAS resulted in denser inner film structures, at least partially due to ionic interactions between the positively charged quaternary ammonium groups and the negatively charged SiO(-) groups. This resulted in lower water uptake, reduced water vapor permeability and decreasing apparent compound diffusivities. In contrast, the affinity of the investigated drugs and parabens to the films substantially increased upon MAS addition. The obtained new knowledge can be helpful for the development of novel coating materials (based on QPM-MAS blends) for controlled-release dosage forms. PMID:26004005

  19. Antimicrobial activity of bone cements embedded with organic nanoparticles

    PubMed Central

    Perni, Stefano; Thenault, Victorien; Abdo, Pauline; Margulis, Katrin; Magdassi, Shlomo; Prokopovich, Polina

    2015-01-01

    Infections after orthopedic surgery are a very unwelcome outcome; despite the widespread use of antibiotics, their incidence can be as high as 10%. This risk is likely to increase as antibiotics are gradually losing efficacy as a result of bacterial resistance; therefore, novel antimicrobial approaches are required. Parabens are a class of compounds whose antimicrobial activity is employed in many cosmetic and pharmaceutical products. We developed propylparaben nanoparticles that are hydrophilic, thus expanding the applicability of parabens to aqueous systems. In this paper we assess the possibility of employing paraben nanoparticles as antimicrobial compound in bone cements. The nanoparticles were embedded in various types of bone cement (poly(methyl methacrylate) [PMMA], hydroxyapatite, and brushite) and the antimicrobial activity was determined against common causes of postorthopedic surgery infections such as: Staphylococcus aureus, methicillin-resistant S. aureus, Staphylococcus epidermidis, and Acinetobacter baumannii. Nanoparticles at concentrations as low as 1% w/w in brushite bone cement were capable of preventing pathogens growth, 5% w/w was needed for hydroxyapatite bone cement, while 7% w/w was required for PMMA bone cement. No detrimental effect was determined by the addition of paraben nanoparticles on bone cement compression strength and cytocompatibility. Our results demonstrate that paraben nanoparticles can be encapsulated in bone cement, providing concentration-dependent antimicrobial activity; furthermore, lower concentrations are needed in calcium phosphate (brushite and hydroxyapatite) than in acrylic (PMMA) bone cements. These nanoparticles are effective against a wide spectrum of bacteria, including those already resistant to the antibiotics routinely employed in orthopedic applications, such as gentamicin. PMID:26487803

  20. Determination of micropollutants in combined sewer overflows and their removal in a wastewater treatment plant (Seoul, South Korea).

    PubMed

    Ryu, Jaena; Oh, Jeill; Snyder, Shane A; Yoon, Yeomin

    2014-05-01

    The present study investigated the occurrence of 29 selected micropollutants such as endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPs) in surface waters and wastewaters in Seoul (South Korea) during both dry and wet weather conditions. The study area was selected based on the lack of available information regarding the suspected contamination of rivers/creeks by EDCs and PPCPs in the Seoul region and the presence of a wastewater treatment plant (WWTP), which serves approximately 4.1 million inhabitants and has a design capacity of 1,297 × 10(3) m(3)/day. Many target compounds (83 %) were detected in samples collected from wastewater treatment influent/effluent, creek water, and combined sewer overflow (CSO). The total EDC/PPCP concentrations were as follows: WWTP influent (69,903 ng/L) > WWTP effluent (50,175 ng/L) >3 creek samples (16,035-44,446 ng/L) during dry weather, and WWTP influent (53,795 ng/L) > WWTP bypass (38,653 ng/L) >5 creek samples (15,260-29,113 ng/L) >2 CSO samples (11,109-11,498 ng/L) during wet weather. EDCs and PPCPs were found to be present at high daily loads (65.1 and 69.8 kg/day during dry and wet weather, respectively) in the WWTP effluent. Compound removal by the WWTP varied significantly by compound: caffeine, diclofenac, ibuprofen, naproxen, and propylparaben (>90 %), and acesulfame, DEET, iohexol, iopromide, and iopamidol (<5 %). These findings and literature information support the hypothesis that the efficiency of removal of EDCs and PPCPs is strongly dependent on both removal mechanism (e.g., biodegradation, adsorption to sludge, and oxidation by chlorine) and compound physicochemical properties (e.g., pK a and hydrophobicity). PMID:24415065

  1. Establishing the importance of oil-membrane interactions on the transmembrane diffusion of physicochemically diverse compounds.

    PubMed

    Najib, Omaima N; Martin, Gary P; Kirton, Stewart B; Sallam, Al-Sayed; Murnane, Darragh

    2016-06-15

    The diffusion process through a non-porous barrier membrane depends on the properties of the drug, vehicle and membrane. The aim of the current study was to investigate whether a series of oily vehicles might have the potential to interact to varying degrees with synthetic membranes and to determine whether any such interaction might affect the permeation of co-formulated permeants: methylparaben (MP); butylparaben (BP) or caffeine (CF). The oils (isopropyl myristate (IPM), isohexadecane (IHD), hexadecane (HD), oleic acid (OA) and liquid paraffin (LP)) and membranes (silicone, high density polyethylene and polyurethane) employed in the study were selected such that they displayed a range of different structural, and physicochemical properties. Diffusion studies showed that many of the vehicles were not inert and did interact with the membranes resulting in a modification of the permeants' flux when corrected for membrane thickness (e.g. normalized flux of MP increased from 1.25±0.13μgcm(-1)h(-1) in LP to 17.94±0.25μgcm(-1)h(-1)in IPM). The oils were sorbed differently to membranes (range of weight gain: 2.2±0.2% for polyurethane with LP to 105.6±1.1% for silicone with IHD). Membrane interaction was apparently dependent upon the physicochemical properties including; size, shape, flexibility and the Hansen solubility parameter values of both the membranes and oils. Sorbed oils resulted in modified permeant diffusion through the membranes. No simple correlation was found to exist between the Hansen solubility parameters of the oils or swelling of the membrane and the normalized fluxes of the three compounds investigated. More sophisticated modelling would appear to be required to delineate and quantify the key molecular parameters of membrane, permeant and vehicle compatibility and their interactions of relevance to membrane permeation. PMID:27012979

  2. Prenatal Exposure to Phenols and Growth in Boys

    PubMed Central

    Philippat, Claire; Botton, Jérémie; Calafat, Antonia M.; Ye, Xiaoyun; Charles, Marie-Aline; Slama, Rémy

    2016-01-01

    Background Phenols interact with nuclear receptors implicated in growth and adipogenesis regulation. Only a few studies have explored their effects on growth in humans. Objectives We studied the associations of maternal exposure to phenols during pregnancy with prenatal and postnatal growth of male newborns. Methods Within a cohort of women recruited during pregnancy, we selected 520 mother–son pairs and quantified 9 phenols in spot urine samples collected during pregnancy. We used ultrasonography during pregnancy, together with birth measurements, to assess fetal growth. We modeled individual postnatal growth trajectories from repeated measures of weight and height in the first 3 years of life. Results Triclosan concentration was negatively associated with growth parameters measured at the third ultrasound examination but not earlier in pregnancy. At birth, this phenol tended to be negatively associated with head circumference (−1.2 mm for an interquartile range [IQR] increase in ln-transformed triclosan concentration [95% confidence interval = −2.6 to 0.3]) but not with weight or height. Parabens were positively associated with weight at birth. This positive association remained for 3 years for methylparaben (β = 193 g [−4 to 389]) for an IQR increase in ln-transformed concentrations. Conclusion We relied on only 1 spot urine sample to assess exposure; because of the high variability in phenol urinary concentrations reported during pregnancy, using only 1 sample may result in exposure misclassification, in particular for bisphenol A. Our study suggested associations between prenatal exposure to parabens and triclosan and prenatal or early postnatal growth. PMID:25061923

  3. Comparative study of the hydrolytic metabolism of methyl-, ethyl-, propyl-, butyl-, heptyl- and dodecylparaben by microsomes of various rat and human tissues.

    PubMed

    Ozaki, Hitomi; Sugihara, Kazumi; Watanabe, Yoko; Fujino, Chieri; Uramaru, Naoto; Sone, Tomomichi; Ohta, Shigeru; Kitamura, Shigeyuki

    2013-12-01

    Hydrolytic metabolism of methyl-, ethyl-, propyl-, butyl-, heptyl- and dodecylparaben by various tissue microsomes and plasma of rats, as well as human liver and small-intestinal microsomes, was investigated and the structure-metabolic activity relationship was examined. Rat liver microsomes showed the highest activity toward parabens, followed by small-intestinal and lung microsomes. Butylparaben was most effectively hydrolyzed by the liver microsomes, which showed relatively low hydrolytic activity towards parabens with shorter and longer alkyl side chains. In contrast, small-intestinal microsomes exhibited relatively higher activity toward longer-side-chain parabens, and showed the highest activity towards heptylparaben. Rat lung and skin microsomes showed liver-type substrate specificity. Kidney and pancreas microsomes and plasma of rats showed small-intestinal-type substrate specificity. Liver and small-intestinal microsomal hydrolase activity was completely inhibited by bis(4-nitrophenyl)phosphate, and could be extracted with Triton X-100. Ces1e and Ces1d isoforms were identified as carboxylesterase isozymes catalyzing paraben hydrolysis by anion exchange column chromatography of Triton X-100 extract from liver microsomes. Ces1e and Ces1d expressed in COS cells exhibited significant hydrolase activities with the same substrate specificity pattern as that of liver microsomes. Small-intestinal carboxylesterase isozymes Ces2a and Ces2c expressed in COS cells showed the same substrate specificity as small-intestinal microsomes, being more active toward longer-alkyl-side-chain parabens. Human liver microsomes showed the highest hydrolytic activity toward methylparaben, while human small-intestinal microsomes showed a broadly similar substrate specificity to rat small-intestinal microsomes. Human CES1 and CES2 isozymes showed the same substrate specificity patterns as human liver and small-intestinal microsomes, respectively. PMID:23742084

  4. Fast and sensitive method to determine parabens by capillary electrophoresis using automatic reverse electrode polarity stacking mode: application to hair samples.

    PubMed

    Sako, Alysson V F; Dolzan, Maressa D; Micke, Gustavo Amadeu

    2015-09-01

    This paper describes a fast and sensitive method for the determination of methyl, ethyl, propyl, and butylparaben in hair samples by capillary electrophoresis using automatic reverse electrode polarity stacking mode. In the proposed method, solutions are injected using the flush command of the analysis software (940 mbar) and the polarity switching is carried out automatically immediately after the sample injection. The advantages compared with conventional stacking methods are the increased analytical frequency, repeatability, and inter-day precision. All analyses were performed in a fused silica capillary (50 cm, 41.5 cm in effective length, 50 μm i.d.), and the background electrolyte was composed of 20 mmol L(-1) sodium tetraborate in 10 % of methanol, pH 9.3. For the reverse polarity, -25 kV/35 s was applied followed by application of +30 kV for the electrophoretic run. Temperature was set at 20 °C, and all analytes were monitored at 297 nm. The method showed acceptable linearity (r (2) > 0.997) in the studied range of 0.1-5.0 mg L(-1), limits of detection below 0.017 mg L(-1), and inter-day, intra-day, and instrumental precision better than 6.2, 3.6, and 4.6 %, respectively. Considering parabens is widely used as a preservative in many products and the reported possibility of damage to the hair and also to human health caused by these compounds, the proposed method was applied to evaluate the adsorption of parabens in hair samples. The results indicate that there is a greater adsorption of methylparaben compared to the other parabens tested and also dyed hairs had a greater adsorption capacity for parabens than natural hairs. PMID:26168974

  5. Preparation and evaluation of monolithic poly(N-vinylcarbazole-co-1,4-divinylbenzene) capillary columns for the separation of small molecules.

    PubMed

    Koeck, Rainer; Fischnaller, Martin; Bakry, Rania; Tessadri, Richard; Bonn, Guenther K

    2014-09-01

    Short-term polymerization or the so-called low-conversion polymerization was applied for the preparation of N-vinylcarbazole (NVC) and 1,4-divinylbenzene (DVB) monolithic capillary columns. The synthesis was carried out by thermally initiated free radical copolymerization under the influence of inert micro- (toluene) and macroporogen (1-decanol) and α,α'-azoisobutyronitrile (AIBN) as radical initiator. The morphological and porous properties were studied by scanning electron microscopy (SEM), nitrogen adsorption, and mercury intrusion porosimetry (MIP). The copolymerization process was studied by monomer conversion measurements. This approach led to increased porosity and specific surface area. A specific surface area above 400 m(2)/g of the monolith and a distinct bimodal pore size distribution were obtained. The chromatographic performance was determined in terms of theoretical plate heights and number of theoretical plates. The lowest plate height value was found to be 3.9 μm (corresponding to ≈256,000 plates per meter) applying methylparaben utilizing an 80 mm × 0.2 mm i.d. monolithic capillary. The developed NVC/DVB monolithic supports showed high separation efficiency towards small molecules, which was exemplified applying reversed-phase (RP) separation of alkylbenzenes, beta-blockers, flavanoids, parabens, and phenones. The loading capacity was analyzed for isocratic separation of seven alkylbenzenes and was found to be up to 77 ng total mass of alkylbenzenes. Furthermore, a long-term stability test of 1,000 consecutive runs was performed and resulted in a maximum variance of 0.97, 0.85, and 0.16 % RSD for resolution, peak width at half height, and retention times, respectively. The material was proven to have a high permeability of 1.11E-14 m(2), applying water as a mobile phase. PMID:25056873

  6. Simultaneous determination of some water-soluble vitamins and preservatives in multivitamin syrup by validated stability-indicating high-performance liquid chromatography method.

    PubMed

    Vidović, Stojanka; Stojanović, Biljana; Veljković, Jelena; Prazić-Arsić, Ljiljana; Roglić, Goran; Manojlović, Dragan

    2008-08-22

    HPLC stability-indicating method has been developed for the simultaneous determination of some water-soluble vitamins (ascorbic acid, thiamine hydrochloride, riboflavin-5'-phosphate sodium, pyridoxine hydrochloride, nicotinamide, D(+)-panthenol) and two preservatives (methylparaben and sodium benzoate) in multivitamin syrup preparation. Water-soluble vitamins, preservatives and their degradants were separated on Zorbax SB-Aq (C(18)) (250 mm x 4.6 mm, 5 microm) column at an ambient temperature. Combined isocratic and gradient elution was performed with a mobile phase consisting of 0.0125 M hexane-1-sulfonic acid sodium salt in 0.1% (m/v) o-phosphoric acid, pH 2.4-2.5 (solvent A) and acetonitrile (solvent B) at the flow-rate 1 ml min(-1). Starting with solvent A an isocratic elution was performed for 15 min, then the composition was changed to 85% of A and 15% of B during the next 20 min and it was constant for 5 min, then the composition was changed to 70% of A and 30% of B during next 15 min and it was constant for 5 min and finally was changed to 100% of A as at the beginning of the elution. Detection was performed with diode array detector at 210, 230 and 254 nm. Multivitamin syrup preparation was subjected to stress testing (forced degradation) in order to demonstrate that degradants from the vitamins, preservatives and/or product excipients do not interfere with the quantification of vitamins and preservatives. Typical validation characteristics: selectivity, accuracy, precision, linearity, range, limit of quantification and limit of detection were evaluated for vitamins and preservatives. PMID:18644604

  7. Nutrients versus emerging contaminants-Or a dynamic match between subsidy and stress effects on stream biofilms.

    PubMed

    Aristi, I; Casellas, M; Elosegi, A; Insa, S; Petrovic, M; Sabater, S; Acuña, V

    2016-05-01

    Freshwater ecosystems are threatened by multiple anthropogenic stressors, which might be differentiated into two types: those that reduce biological activity at all concentrations (toxic contaminants), and those that subsidize biological activity at low concentrations and reduce it at high concentrations (assimilable contaminants). When occurring in mixtures, these contaminants can have either antagonistic, neutral or synergistic effects; but little is known on their joint effects. We assessed the interaction effects of a mixture of assimilable and toxic contaminants on stream biofilms in a manipulative experiment using artificial streams, and following a factorial design with three nutrient levels (low, medium or high) and either presence or absence of a mixture of emerging contaminants (ciprofloxacin, erythromycin, diclofenac, methylparaben, and sulfamethoxazole). We measured biofilm biomass, basal fluorescence, gross primary production and community respiration. Our initial hypotheses were that biofilm biomass and activity would: increase with medium nutrient concentrations (subsidy effect), but decrease with high nutrient concentrations (stress effect) (i); decrease with emerging contaminants, with the minimum decrease at medium nutrient concentrations (antagonistic interaction between nutrients subsidy and stress by emerging contaminants) and the maximum decrease at high nutrient concentrations (synergistic interaction between nutrients and emerging contaminants stress) (ii). All the measured variables responded linearly to the available nutrients, with no toxic effect at high nutrient concentrations. Emerging contaminants only caused weak toxic effects in some of the measured variables, and only after 3-4 weeks of exposure. Therefore, only antagonistic interactions were observed between nutrients and emerging contaminants, as medium and high nutrient concentrations partly compensated the harmful effects of emerging contaminants during the first weeks of the

  8. A novel complex of a phenolic derivative with insulin: structural features related to the T-->R transition.

    PubMed Central

    Smith, G. D.; Ciszak, E.; Pangborn, W.

    1996-01-01

    The structure of a symmetric T3R3f insulin hexamer, complexed with 4-hydroxybenzamide, has been determined using X-ray crystallographic techniques. Data were measured from six crystals grown in microgravity to a resolution of 1.4 A and the structure has been refined including the contributions from hydrogen atoms. The crystals are isomorphous with T3R3f complexes of phenolic derivatives as well as with uncomplexed forms. Unlike the structures of complexes with phenol, m-cresol, resorcinol, 4'-hydroxyacetanilide, and methylparaben, which bind one phenolic derivative molecule per R- or Rf-state monomer, two molecules of 4-hydroxybenzamide are bound by each Rf-state monomer. The presence of the second guest molecule results in an extensive hydrogen bonding network, mediated by water molecules, between the T- and Rf-state trimers and adds stability to the formation of the hexamer. The only access to these second sites is through three symmetry-related, narrow channels that originate on the surface of the T-state trimer. Although the conformation of the backbone atoms of the monomers is nearly identical to that of other T3R3f hexamers, significant changes are observed in the conformations of side chains in the vicinity of the second binding site. The side chain of the T-state A11 Cys residue, which forms a disulfide bond to A6 Cys in the same monomer, is observed in two discrete conformations; two discrete conformations are also present for the entire A8 Thr residue in the Rf-state monomer. A procedure is also described for an alternate method of interframe scaling and merging intensity data from an image plate detector. PMID:8844841

  9. Prediction of preservative sensitization potential using surface marker CD86 and/or CD54 expression on human cell line, THP-1.

    PubMed

    Sakaguchi, Hitoshi; Miyazawa, Masaaki; Yoshida, Yukiko; Ito, Yuichi; Suzuki, Hiroyuki

    2007-02-01

    Preservatives are important components in many products, but have a history of purported allergy. Several assays [e.g., guinea pig maximization test (GPMT), local lymph node assay (LLNA)] are used to evaluate allergy potential of preservatives. We recently developed the human Cell Line Activation Test (h-CLAT), an in vitro skin sensitization test using human THP-1 cells. This test evaluates the augmentation of CD86 and CD54 expression, which are key events in the sensitization process, as an indicator of allergy following treatment with test chemical. Earlier, we found that a sub-toxic concentration was needed for the up-regulation of surface marker expression. In this study, we further evaluate the capability of h-CLAT to predict allergy potential using eight preservatives. Cytotoxicity was determined using propidium iodide with flow cytometry analysis and five doses that produce a 95, 85, 75, 65, and 50% cell viability were selected. If a material did not have any cytotoxicity at the highest technical dose (HTD), five doses are set using serial 1.3 dilutions of the HTD. The test materials used were six known allergic preservatives (e.g., methylchloroisothiazolinone/methylisothiazolinone, formaldehyde), and two non-allergic preservatives (methylparaben and 4-hydroxybenzoic acid). All allergic preservatives augmented CD86 and/or CD54 expression, indicating h-CLAT correctly identified the allergens. No augmentation was observed with the non-allergic preservatives; also correctly identified by h-CLAT. In addition, we report two threshold concentrations that may be used to categorize skin sensitization potency like the LLNA estimated concentration that yield a three-fold stimulation (EC3) value. These corresponding values are the estimated concentration which gives a relative fluorescence intensity (RFI) = 150 for CD86 and an RFI = 200 for CD54. These data suggest that h-CLAT, using THP-1 cells, may be able to predict the allergy potential of preservatives and

  10. The metal-organic framework HKUST-1 as efficient sorbent in a vortex-assisted dispersive micro solid-phase extraction of parabens from environmental waters, cosmetic creams, and human urine.

    PubMed

    Rocío-Bautista, Priscilla; Martínez-Benito, Carla; Pino, Verónica; Pasán, Jorge; Ayala, Juan H; Ruiz-Pérez, Catalina; Afonso, Ana M

    2015-07-01

    Three metal-organic frameworks (MOFs), specifically HKUST-1, MOF-5, and MIL-53(Al), have been synthetized, characterized, studied and compared in a vortex-assisted dispersive micro-solid-phase extraction (VA-D-µ-SPE) procedure in combination with high-performance liquid chromatography (HPLC) with diode-array detection (DAD) for determining seven parabens in environmental waters (tap water, swimming pool water, and water coming from a spa pool), human urine (from two volunteers), and cosmetic creams (two commercial brands). Experimental parameters, such as nature and amount of MOF, sample volume, nature of elution solvent and its amount, vortex and centrifugation time, among others, were properly optimized. HKUST-1 was the most adequate MOF to work with. Detection limits for the overall method down to 0.1 μgL(-1) for butylparaben (BPB) and benzylparaben (BzPB) were obtained, with determination coefficients (R(2)) higher than 0.9966 for a range of 0.5-147 μgL(-1) (depending on the paraben), average relative recoveries (RR, in %) of 80.3% at the low spiked level (7 μgL(-1)), and relative standard deviation (RSD) values below 10% also at the low spiked level. The strength of the affinity between HKUST-1 and parabens was evaluated, and it ranged from 33.5% for isopropylparaben (iPPB) to 77.0% for isobutylparaben (iBPB). When analyzing complex environmental waters, RR values of 78%, inter-day precision values (as RSD) lower than 15%, and intra-day precision values lower than 7.8% were obtained, despite the observed matrix effect. When analyzing cosmetic creams, parabens were detected, with contents ranging from 0.14 ± 0.01 μgg(-1) for EPB in the healing cream analyzed to 1.12 ± 0.07 mgg(-1) for MPB in the mask cream analyzed, with precision values (RSD) lower than 12% and RR values from 63.7% for propylparaben (PPB) to 121% for iPPB. When analyzing human urine, no parabens were detected but the method could be performed with RSD values lower than 19%. These

  11. Non-parametric linear regression of discrete Fourier transform convoluted chromatographic peak responses under non-ideal conditions of internal standard method.

    PubMed

    Korany, Mohamed A; Maher, Hadir M; Galal, Shereen M; Fahmy, Ossama T; Ragab, Marwa A A

    2010-11-15

    This manuscript discusses the application of chemometrics to the handling of HPLC response data using the internal standard method (ISM). This was performed on a model mixture containing terbutaline sulphate, guaiphenesin, bromhexine HCl, sodium benzoate and propylparaben as an internal standard. Derivative treatment of chromatographic response data of analyte and internal standard was followed by convolution of the resulting derivative curves using 8-points sin x(i) polynomials (discrete Fourier functions). The response of each analyte signal, its corresponding derivative and convoluted derivative data were divided by that of the internal standard to obtain the corresponding ratio data. This was found beneficial in eliminating different types of interferences. It was successfully applied to handle some of the most common chromatographic problems and non-ideal conditions, namely: overlapping chromatographic peaks and very low analyte concentrations. For example, a significant change in the correlation coefficient of sodium benzoate, in case of overlapping peaks, went from 0.9975 to 0.9998 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. Also a significant improvement in the precision and accuracy for the determination of synthetic mixtures and dosage forms in non-ideal cases was achieved. For example, in the case of overlapping peaks guaiphenesin mean recovery% and RSD% went from 91.57, 9.83 to 100.04, 0.78 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. This work also compares the application of Theil's method, a non-parametric regression method, in handling the response ratio data, with the least squares parametric regression method, which is considered the de facto standard method used for regression. Theil's method was found to be superior to the method of least squares as it assumes that errors could occur in both x- and y-directions and

  12. Ecological risks of home and personal care products in the riverine environment of a rural region in South China without domestic wastewater treatment facilities.

    PubMed

    Zhang, Nai-Sheng; Liu, You-sheng; Van den Brink, Paul J; Price, Oliver R; Ying, Guang-Guo

    2015-12-01

    Home and personal care products (HPCPs) including biocides, benzotriazoles (BTs) and ultraviolet (UV) filters are widely used in our daily life. After use, they are discharged with domestic wastewater into the receiving environment. This study investigated the occurrence of 29 representative HPCPs, including biocides, BTs and UV filters, in the riverine environment of a rural region of South China where no wastewater treatment plants were present, and assessed their potential ecological risks to aquatic organisms. The results showed the detection of 11 biocides and 4 BTs in surface water, and 9 biocides, 3 BTs and 4 UV filters in sediment. In surface water, methylparaben (MeP), triclocarban (TCC), and triclosan (TCS) were detected at all sites with median concentrations of 9.23 ng/L, 2.64 ng/L and 5.39 ng/L, respectively. However, the highest median concentrations were found for clotrimazole (CLOT), 5-methyl-1H-benzotriazole (MBT) and carbendazim (CARB) at 55.6 ng/L, 33.7 ng/L and 13.8 ng/L, respectively. In sediment, TCC, TCS, and UV-326 were detected with their maximum concentrations up to 353 ng/g, 155 ng/g, and 133 ng/g, respectively. The concentrations for those detected HPCPs in surface water and sediment were generally lower in the upper reach (rural area) of Sha River than in the lower reach of Sha River with close proximity to Dongjiang River (Pt-test<0.05), indicating other input sources of HPCPs in the lower reach. Biocides showed significantly higher levels in surface water in the wet season than in the dry and intermediate seasons. Preliminary risk assessment demonstrated that the majority of HPCPs monitored represented low risk in surface waters. There are potentially greater risks to aquatic organisms from the use of TCS and TCC in the wet season than in dry and intermediate seasons in surface waters. This preliminary assessment also indicates potential concerns associated with TCC, TCS, DEET, CARB, and CLOT in sediments, although additional data