Methyl Propyl Research Articles

An ultra-long stability of lanthanum (La) modified molecular sieve for catalytic degradation of typical sulfur-containing VOCs in a near-real environment

The catalytic degradation of typical sulfur-containing VOCs, ethyl mercaptan (C2H5SH), in a near-real environment remains a challenge task. In this study, an ultra-long stability of 600 h for degradation of C2H5SH was obtained over La doped ZSM-5, and the corresponding catalytic performance, reaction and deactivation mechanism were investigated by a series of ex situ and in situ characterizations. Furthermore, the influence law of other low-carbon mercaptans, such as methyl mercaptan (CH3SH), propyl mercaptan (C3H7SH), and butyl mercaptan (C4H9SH) as well as the moisture on their stability were investigated. The slight deactivation by designed experiment revealed a distinguished reversible moisture-induced deactivation mechanism, where moisture promoted the formation of carbonate related species that covers the active sites, while this deactivation could be recovered by a simple temperature-lifting strategy. This work provides a theoretical guidance for catalytic degradation of mixed sulfur-containing VOCs under the presence of moisture.

Identification of N-(3-(methyl(3-(orotic amido)propyl)amino)propyl) oleanolamide as a novel topoisomerase I catalytic inhibitor by rational design, molecular dynamics simulation, and biological evaluation

DNA topoisomerase I (TOP1) catalytic inhibitors are a promising class of antitumor agents. Oleanolic acid derivatives are potential TOP1 catalytic inhibitors. However, their inhibitory activity still needs to be enhanced, and the stability and hotspot residue sites of their interaction with TOP1 remain to be elucidated. Herein, a novel oleanolic acid derivative, OA4 (N-(3-(methyl(3-(orotic amido)propyl)amino)propyl)oleanolamide), was identified by rational design. Subsequently, molecular dynamics simulations were performed to explore the stability and conformational dynamics of the TOP1–OA4 complex. The molecular mechanics/generalized Born surface area method calculated the binding free energy and predicted Arg488, Ile535, and His632 to be hotspot residues. Biological experiments verified that OA4 is a nonintercalative TOP1 catalytic inhibitor. OA4 exhibits better proliferation inhibitory activity against tumor cells than normal cells. Furthermore, OA4 can induce apoptosis and effectively suppress the proliferation and migration of cancer cells. This work provides new insights for the development of novel TOP1 catalytic inhibitors.

Lipid extraction and analysis of microalgae strain pectinodesmus PHM3 for biodiesel production

The current study is focused on the lipid extract of microalgae; Pectinodesmus strain PHM3 and its general analysis in terms of chemical contents. Combinations of both chemical and mechanistic approaches were applied to obtain the maximum yield of lipids which was recorded to be 23% per gram through continuous agitation using Folch solution. The extraction methods used in this study included: Bligh and Dyers method, Continuous agitation method, Extraction using Soxhlet and Acid base extraction method. Lipid quantification of ethanol and Folch solution lipid extract was performed through gravimetric methods and qualification was done through Fourier Transmission Infrared Spectroscopy (FTIR) and Gas Chromatographymass spectrometry (GC-MS). Phytochemical analysis identified other compounds in ethanol extract and the results confirmed the presence of steroids, coumarins, tannins, phenols and carbohydrates. Transesterification of lipids showed 7% per gram dry weight yield of Pectinodesmus PHM3. GC-MS studies of extracted biodiesel suggested that 72% of biofuels was in the form of dipropyl ether, ethyl butyl ethers, methyl butyl ether and propyl butyl ether. Lipid processing of acid-base extract showed that oily nature of lipid shifted to a more precipitated form which is a common observation when mixture of lipids is converted to phosphatides.

Determination of seven paraben preservatives in aquatic seasoning using solid-phase extraction coupled with high performance liquid chromatography

Seven parabens are widely used in soy sauce, vinegar, jam, oyster sauce, stuffing, and other foods. The long-term intake of large amounts of parabens and similar substances may be harmful to the human body. Therefore, the addition of paraben preservatives to food should be strictly controlled. The current detection method is applicable to single target compound and several food categories, and the experimental pretreatment method involves extraction with anhydrous ethyl ether, which is a toxic reagent. Moreover, interferences in the analysis of parabens via gas chromatography limit the versatility and accuracy of the detection method. Herein, a novel method based on solid-phase extraction (SPE) coupled with high performance liquid chromatography (HPLC) was developed for the determination of seven paraben preservatives (methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate, and heptyl p-hydroxybenzoate) in oyster sauce, shrimp sauce, and fish sauce. Compared with the conventional method, the proposed work enables the determination of more compounds, thereby expanding its scope of application to different food types. This strategy also optimizes the pretreatment method and device parameters. The samples were extracted with methanol and 20% methanol aqueous solution by ultrasonication, respectively, and then centrifuged. The experimental pretreatment method was enriched, and sample clean-up was conducted using a MAX SPE column. The seven parabens were separated using a Chromcore 120 C18 column (150 mm×4.6 mm, 3.0 μm). Gradient elution was performed with acetonitrile-5 mmol/L ammonium acetate aqueous solution as the mobile phase (initial mobile phase volume ratio, 30∶70). The flow rate was 0.7 mL/min, and the column temperature was 35 ℃. A diode array detector with a detection wavelength of 254 nm was also used. The seven paraben preservatives showed good linearity in the range of 0.5-50.0 mg/L, with correlation coefficients greater than 0.9999. The limits of detection (LODs) and quantification (LOQs) for the seven paraben preservatives were 0.2-0.4 mg/kg and 0.5-1.3 mg/kg, respectively. A spiked recovery test was conducted using oyster sauce, shrimp sauce, and fish sauce at three spiked levels of 2, 40, and 200 mg/kg. Good recoveries for the seven paraben preservatives were obtained and the recoveries of the analytes in oyster sauce, shrimp sauce, and fish sauce were 91.0%-102%, 95.5%-106%, and 95.0%-105%, respectively, with relative standard deviations of ≤6.97%. Compared with the liquid-liquid extraction method, the proposed method demonstrated better purification effects. The recoveries of the seven paraben preservatives extracted using this method were also much higher than those obtained from liquid-liquid extraction. We determined the contents of these preservatives in 135 food products using the method established in this study and detected methyl p-hydroxybenzoate and ethyl p-hydroxybenzoate in soy sauce, vinegar, and pickles. Thus, the established method can be used for the effective determination of seven parabens in aquatic seasoning such as oyster sauce, shrimp sauce, and fish sauce.

Green micellar stability-indicating high-performance liquid chromatography method for determination of rupatadine fumarate in the presence of its main impurity desloratadine: Oxidative degradation kinetics study.

A green micellar stability-indicating high-performance liquid chromatography method was developed for rupatadine fumarate determination in existence with its main impurity desloratadine. Separation was attained using Hypersil ODS column (150×4.6mm, 5μm), the micellar mobile phase consisted of 0.13M sodium dodecyl sulfate, 0.1M disodium hydrogen phosphate adjusted by phosphoric acid to pH 2.8 and 10% n-butanol. The column was maintained at 45◦ C and detection was carried out at 267nm. A linear response was achieved over the range of 2-160μg/ml for rupatadine and 0.4-8μg/ml for desloratadine. The method was applied for rupatadine determination in alergoliber tablets and alergoliber syrup without the interference of methyl paraben and propyl paraben present as main excipients. Rupatadine fumarate revealed pronounced susceptibility to oxidation; further study of oxidative degradation kinetics was carried out. Rupatadine was found to follow pseudo-first-order kinetics when exposed to 10% H2 O2 at 60 and 80°C and the activation energy was found to be 15.69Kcal/mol. At a lower temperature (40°C), degradation kinetics regression was best fitted as a polynomial quadratic relationship, thus rupatadine oxidation at a lower temperature tends to adopt a second-order kinetics rate. Oxidative degradation product structure was revealed using infrared and found to be rupatadine N-oxide at all temperature values.

Boundary layer effect of light transmission through ionic liquid under electric field

The field strength distribution in the ionic liquid boundary layer under the action of an external electric field is non-uniform. Whether its transmittance (absorption coefficient) spatially varies arouses our interest in exploring the underlying laws. In this paper, with the help of an infrared microscope, a special experimental device was designed and established. The transmittance in the ionic liquid (methyl propyl imidazole iodide, C3MImI) at different distances from the electrodes (cathode, anode) was measured under electric voltages from 0 V to 0.5 V. Results showed that transmittances of ionic liquid at the boundary layer present nonlinear change with the nonlinear electronic strength under the different applied voltage, and there is a critical threshold (0.2 V) distinguishes the sensitive and non-sensitive responses to the electric field. Our study provides a physical basis for microscale electro-optic regulation and is significant, especially for precise regulation of light field transmittance in micro-nano channels/structures.

Reactive extraction of protocatechuic acid by di-n-octylamine and optimisation with Box–Behnken design

ABSTRACT Protocatechuic acid (PCA) is typically produced by microbial fermentation. Its separation from fermentation broth or aqueous waste streams is of great importance. This study aimed to recover PCA by a secondary amine namely di-n-octylamine (DOA). Three organic solvents, namely isobutyl methyl ketone, propyl acetate and linalool, were used with DOA. Important extraction parameters were optimised by response surface methodology. DOA/isobutyl methyl ketone system showed 95.84% extraction efficiency under the optimum conditions. The maximum E% of the DOA/propyl acetate system was 86.73%. The maximum E% of the DOA/linalool system was 81.71%. Additionally, a thermodynamic study was carried out, and the reactions were endothermic. Highlights Protocatechuic extraction by di-n-octylamine has been done first in the literature. Different kinds of solvents have been used to solve di-n-octylamine. Useful information is obtained for the design of protocatechuic acid reactive extraction.

The perturbation of parabens on the neuroendocrine system in zebrafish larvae

Parabens, as the synthetic preservatives, have caused universal environmental contamination and human exposure. Whether parabens could disturb neuroendocrine system was still ambiguous. In this study, the effects of four commonly-used parabens, i.e. methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP), were tested on the neuroendocrine system of zebrafish larvae by investigating the swimming behavior, the related hormones and biomarkers in the hypothalamic-pituitary-interrenal (HPI) axis. The results showed that all test chemicals significantly reduced the swimming distance and mean velocity of zebrafish larvae. The adrenocorticotropic hormone (ACTH) levels in zebrafish larvae were significantly increased, while the cortisol levels were obviously decreased by paraben exposure. The transcriptional analysis showed that the expressions of the target genes including gr, mr and crhr2 in the HPI axis were mostly down-regulated. The exploration of the initial molecular event showed that parabens could bind with the glucocorticoid receptor (GR) and trigger its transactivation, according to MDA-kb2 luciferase assay and molecular docking analysis. The interaction of parabens with the GR included the hydrogen bond and hydrophobic interaction. The findings herein revealed the potential deleterious effects of parabens on the neuroendocrine system of zebrafish larvae, thus accumulating the in vivo toxicological data on this kind of food preservatives.

Effect of Commonly Used Cosmetic Preservatives on Healthy Human Skin Cells

Cosmetic products contain preservatives to prevent microbial growth. The various types of preservatives present in skincare products applied on the skin induce many side effects. We tested several types of preservatives such as phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea (IU), the composition of gluconolactone and sodium benzoate (GSB), diazolidinyl urea (DU), and two grapefruit essential oils, one of which was industrially produced and a second which was freshly distilled from fresh grapefruit peels. This study aimed to find the relationship between preservative concentration, cell growth, collagen secretion, and cell viability. We hypothesized that these products induced a decrease in collagen secretion from human dermal fibroblasts. Our research, for the first time, addressed the overall effect of other preservatives on skin extracellular matrix (ECM) by studying their effect on metalloproteinase-2 (MMP-2) activity. Except for cytotoxicity and contact sensitivity tests, there are no studies of their effect on skin ECM in the available literature. These studies show potential antimicrobial activity, especially from the compounds IU and DU towards reference bacteria and the compounds methyl paraben and propyl paraben against reference fungi. The MTS test showed that fibroblasts are more sensitive to the tested group of preservatives than keratinocytes, which could be caused by the differences between the cells' structures. The grapefruit oils exhibited the most cytotoxicity to both tested cell lines compared to all considered preservatives. The most destructive influence of preservatives on collagen synthesis was observed in the case of IU and DU. In this case, the homemade grapefruit oil turned out to be the mildest one. The results from a diverse group of preservatives show that whether they are natural or synthesized compounds, they require controlled use. Appropriate dosages and evaluation of preservative efficacy should not be the only aspects considered. The complex effect of preservatives on skin processes and cytotoxicity is an important topic for modern people.

Discovery of novel benzenesulfonamides incorporating 1,2,3-triazole scaffold as carbonic anhydrase I, II, IX, and XII inhibitors

Sulfonamides are among the most promising potential inhibitors for carbonic anhydrases (CAs), which are pharmaceutically relevant targets for treating several disease conditions. Herein, a series of benzenesulfonamides bearing 1,2,3-triazole moiety as inhibitors of human (h) α-CAs (hCAs) were designed using the tail approach. The design method combines a benzenesulfonamide moiety with a tail of oxime and a zinc-binding group on a 1,2,3-triazole scaffold. Among the synthesized derivatives, the naphthyl (6m, KI of 68.6 nM, SI of 10.3), and methyl (6a, KI of 56.3 nM, SI of 11.7) derivatives (over hCA IX) and propyl (6c, KI of 95.6 nM, SI of 2.7), and pentyl (6d, KI of 51.1 nM, SI of 6.6) derivatives (over hCA XII) displayed a noticeable selectivity for isoforms hCA I and II, respectively. Meanwhile, derivative 6e displayed a potent inhibitory effect versus the cytosolic isoform hCA I (KI of 47.8 nM) and tumor-associated isoforms hCA IX and XII (KIs of 195.9 and 116.9 nM, respectively) compared with the reference drug acetazolamide (AAZ, KIs of 451.8, 437.2, and 338.9 nM, respectively). Derivative 6b showed higher potency (KI of 33.2 nM) than AAZ (KI of 327.3 nM) towards another cytosolic isoform hCA II. Nevertheless, substituting the lipophilic large naphthyl tail to the 1,2,3-triazole linked benzenesulfonamides (6a-n) raised inhibitory effect versus hCA I and XII and selectivity towards hCA I and II isoforms over hCA IX. Evaluation of the cytotoxic potential of the synthesized derivatives was conducted in L929, MCF-7, and Hep-3B cell lines. Several compounds in the series demonstrated significant antiproliferative activity and minimal cytotoxicity. In the molecular docking study, the sulfonamide moiety interacted with the zinc-ion and neatly fit into the hCAs active sites. The extension of the tail was found to participate in diverse hydrophilic and hydrophobic interactions with adjacent amino acids, ultimately influencing the effectiveness and specificity of the derivatives.

Simultaneous estimation of methyl paraben, propyl paraben, and Bisphenol A in the plasma of Indian pregnant women using liquid chromatography–tandem mass spectrometry

AbstractA selective, rapid, and novel bioanalytical method was developed for the simultaneous determination of methyl paraben, propyl paraben, and Bisphenol A in human plasma with a calibration curve range of 1–100 ng/ml. This method included protein precipitation to ensure extraction along with clean‐up of the complex biometrics. The Chromatographic separation was done using an AccucoreTM aQ liquid chromatography column (Dim. 100×3, particle size: 2.6 µm) with the mobile phase of a mixture consisting of 0.1% formic acid in water: 0.1% formic acid in acetonitrile (03:97, v/v) at a flow rate of 0.300 ml/min. The developed liquid chromatography–tandem mass spectrometry method was further validated utilizing the United States Food and Drug Administration guidelines and all the validation requirements were found to be satisfactory. This proposed method was later successfully utilized to determine the level of the three endocrine‐disrupting compounds in the plasma samples obtained from Indian pregnant women. The results suggest that these women might have been exposed to parabens and Bisphenol A from the use of products such as pharmaceuticals, cosmetics, processed food, and the environment.

THE CHEMICAL COMPOSITION OF PARABEN AND ITS EFFECTS ON HEALTH

Parabens are a group of alkyl esters of p-hydroxybenzoic acid and usually include methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isobutyl paraben, isopropyl paraben and benzyl paraben. Parabens (or their salts) are widely used as preservatives in cosmetics and medicine due to their relatively low toxicity and long history of safe use. Testing of parabens has shown, to varying degrees, that individual paraben compounds have weak estrogenic activity in some in vitro screening tests, such as estrogen receptor ligand binding, regulation of CAT gene expression, and proliferation of MCF-7 cells. Reported in vivo effects include uterine weight gain (eg, butyl, isobutyl, and benzyl parabens) and male reproductive tract effects (eg, butyl and propyl parabens). However, in relation to estrogen as a control during in vivo studies, parabens are much less active than estrogen. While exposure to sufficient doses of exogenous estrogens can increase the risk of certain adverse effects, it is hypothesized that similar risks may arise from exposure to much weaker endocrine-active chemicals (EACs) is still speculation. In evaluating the possibility that exposure to weakly active EACs may be associated with adverse effects due to their endocrine mode of action, it is important to consider both the dose and potency of these compounds compared to estrogen. In this review, a comparative approach involving dose and potency is used to assess whether in utero or adult exposure to parabens may be associated with adverse effects due to their estrogen-modulating mode of action. Keywords: parabens, p-Hydroxybenzoates, PHBA, paraben applications, Methyl paraben.

APPLICATION OF PLACKETT-BURMAN DESIGN FOR DEVELOPMENT AND EVALUATION OF A BETAMETHASONE SUSPENSION FOR INJECTION FORMULATION

Objective: In this study, a quality-by-design (QbD) approach was used to develop a betamethasone suspension for injection formulation and to investigate the possible effects of formulation and process variables on the critical quality attributes (CQAs) of the formulation.
 Material and Method: It was determined that the CQAs of the formulation were particle size distribution, viscosity, sedimentation time, density and assay of active substances and preservatives, considering the quality target product profile (QTPP). Potential risk factors that may affect the CQAs of the formulation were identified using an Ishikawa diagram, and a six-factor, two-level Plackett-Burman experimental design was used to statistically investigate the effects of selected formulation and process variables. The prepared formulations were tested, and variance and multiple linear regression analyses were performed with the acquired data
 Result and Discussion: As a result of the one-way analyses of variance (ANOVA) and multiple linear regression analyses, the established statistical models for the assay of methyl parahydroxybenzoate and propyl parahydroxybenzoate, and viscosity were found to be significant, the established models for other independent variables were not significant. The concentration of carmellose calcium and filter type was found to be the most significant formulation and process variables. In conclusion, this study showed that understanding the formulation and process variables that may affect the CQAs of injectable suspension formulations with a QbD approach could be useful for formulation development and optimization.

Studying paraben-induced estrogen receptor- and steroid hormone-related endocrine disruption effects via multi-level approaches

Increasing concerns have been raised on the health risks of parabens in the regard of their widespread applications and potential endocrine disrupting activities. In this study, four typical parabens, including methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), and butyl paraben (BuP) were systematically investigated for their estrogen receptor- and steroid hormone-related endocrine disruptions using multi-level approaches. Paraben exposure promoted the proliferation of MCF-7 cells, increased the luciferase activity in MVLN cells, and induced the vitellogenin (vtg) expression in zebrafish larvae, showing the typical estrogenic effects. The in vitro protein assays further revealed that PrP and BuP could bind with two isoforms of estrogen receptors (ERs). The estrogenic activities of parabens were predicted to be positively correlated with their chemical structure complexity by using molecular docking analysis. Furthermore, the synthesis and secretion of estradiol (E2) and testosterone (T) were significantly disturbed in H295R cells and zebrafish larvae, which could be regulated by paraben-induced transcriptional disturbance in both in vitro steroidogenesis and in vivo hypothalamic-pituitary-gonadal (HPG) axis. Parabens could disturb the endocrine system by activating the ERs and disrupting the steroid hormone synthesis and secretion, suggesting their potential deleterious risks to the environment and human health.

Development and validation of RP HPLC method for the estimation of methyl paraben sodium and propyl paraben sodium in iron protein succinylate syrup

AbstractA new precise, selective and reliable reversed phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for the determination of Methyl paraben sodium (MPS) and Propyl paraben sodium (PPS) (preservatives) in Iron protein succinylate syrup. Optimized conditions were; Methanol: Water (65: 35) as mobile phase, UV/Vis detector at the wavelength of 254 nm and flow rate was set at 1.3 ml min−1. By applying the set of conditions, separation of components was carried out in less than 7 min for both the analytes. The method was validated according to International conference of Harmonization (ICH) guidelines and the analytical characteristic parameters of validation included specificity, limit of detection (LOD), limit of quantification, linearity, accuracy, precision and robustness were evaluated. The calibration curve was found to be linear in the range of 0.045 mg mL−1 to 0.075 mg mL−1 for Methyl paraben sodium and 0.015 mg mL−1 to 0.025 mg mL−1 for propyl paraben sodium with a correlation coefficient r2 > 0.999. Accuracy; reported as percentage recovery was found to be in the range of 98.71%–101.64% for Methyl paraben sodium and 99.85%–101.47% for Propyl paraben sodium at 80%, 100% and 120% concentration for both the analytes. The proposed method was found to be precise and robust when evaluated by variations in wavelength, mobile phase composition, temperature and analyst. The limit of detection (LOD) was found 0.001 mg mL−1 (3 ppm) for Methyl paraben sodium and 0.001 mg mL−1 (1 ppm) for Propyl paraben sodium.

Experimental study on removal of mercaptans from gas streams by 1-butyl-3-methyl-imidazolyl alanine

Mercaptans as volatile organic sulfur compounds would cause environmental pollution. Researches are focused on the removal of mercaptans by solvent absorption method. In this work, a new efficient absorbent of 1-butyl-3-methylimidazolyl alanine ([Bmim]Ala) was prepared and evaluated by the removal of mercaptans from the model gas containing methyl mercaptan (MeSH, 307.6 mg/m3), ethyl mercaptan (EtSH, 201.1 mg/m3) and propyl mercaptan (PrSH, 149.9 mg/m3) in nitrogen. The results showed that the removal rate of MeSH, EtSH and PrSH was 97.77, 98.12 and 100.00%, respectively, at a temperature of 35 °C and a pressure of 1.00 bar for 2 min. After 6 recycling times, [Bmim]Ala remained a good performance for the removal of mercaptans. The desulfurization mechanism was proposed that the absorption sites were mainly on the alanine anion (Ala−) and Ala− could be replaced by the thiol anion (RS−) to form a new ionic liquid 1-butyl-3-methylimidazolyl thiolate ([Bmim]+RS−). Meanwhile, since the electrostatic interaction between -COO− in Ala− and H-g on the imidazolium cation could be destroyed by the -SH group, the -COO− group would interact with mercaptans to form a strong H-bond. The amino in Ala− and the -SH group could form Lewis acid-base compounds.

Polyoxometalate/reduced graphene oxide composite stabilized on the inner wall of a stainless steel tube as a sorbent for solid-phase microextraction of some parabens followed by quantification via high-performance liquid chromatography

An affordable high-throughput microextraction strategy is presented in the current study. Herein, polyoxometalate/reduced graphene oxide (POM/rGO) composite was prepared and after accommodation on the inner wall of the stainless steel tube, it was used to extract some of the selected parabens such as methyl paraben and propyl paraben from the real samples. The extracted model analytes were desorbed by a suitable organic solvent and quantified by high-performance liquid chromatography-ultraviolet detection (HPLC-UV). The uniform stabilization of POMs on the rGO sheets besides the hydrophobic interactions of rGO with the target analytes increase the extraction efficiency of method. The method validation tests were also performed. According to the obtained data, the linearity of the proposed method was in the range of 1.0–200.0 µg/L (0.2 µg/L < The limits of detection (LODs) < 0.3 µg/L and 0.6 µg/L < limits of quantification (LOQs) < 0.8 µg/L) for the selected parabens. The calibration curves showed the determination of coefficients higher than 0.9954. In order to calculate the precision of the method, the inter-day and intra-day relative standard deviations (RSDs %) were determined between 3.1 and 6.7 % in three concentrations. Furthermore, the enrichment factors were found to be 144 and 152 for methyl paraben and propyl paraben, respectively. Moreover, the calculated absolute recoveries were 72 and 76 % for methyl paraben and propyl paraben, respectively. The proposed method was also employed for the analysis of selected parabens in lipstick, blusher, emollient cream, toothpaste and shampoo. The obtained recoveries indicated that the method was applicable for the microextraction of methyl paraben and propyl paraben from cosmetic products without any interferences.

The key constituents underlying the combined toxicity of eight cosmetic contaminants towards Vibrio qinghaiensis.

Cosmetic additives (ADDs) and packaging plasticizers (PLAs) probably present potential risks and dangers to the environment and human body as emerging pollutants. To investigate their potential risks and dangers, five ADDs including methyl paraben (MET), ethyl paraben (ETH), propyl paraben (PRO), butyl-hydroxy anisole (BHA), and salicylic acid (SAL), as well as three PLAs including bisphenol A (BPA), bisphenol S (BPS) and tris(2-butoxyethyl) phosphate (TBEP) were selected as research objects, and ten mixture rays (R1-R10) composed of the eight components were designed by the uniform design ray (UD-Ray) method. The toxicities of the eight cosmetic pollutants and their eight-component mixture system towards Vibrio qinghaiensis sp.-Q67 (Q67) were systematically determined by the time-dependent microplate toxicity analysis (t-MTA) method. The three-dimensional (3D) surface of deviation from the concentration addition model (dCA) was utilized to qualitatively and quantitatively analyse the toxicity interaction of the mixtures and the correlation between toxicity interaction and the components' concentration ratios. Finally, eight individual pollutants and representative rays with significant inhibitory and interactive effects were selected to analyse DNA and soluble proteolysis as well as the microstructure and morphology of Q67 after treatment with single chemicals and their mixtures. The results showed that the eight cosmetic pollutants had conspicuous concentration-dependent toxicity and acute toxicity, and none of them, except BPS, BPA and ETH, had time-dependent toxicity. All rays had time/concentration-dependent toxicity and acute toxicity. At the same time, the toxicity interaction of these mixture rays was predominantly antagonism and the strongest antagonism appeared at high concentrations at 12 h. Nevertheless, the components' concentration ratio (pi) was the decisive factor for the type of mixture interaction. The correlation analysis revealed a significant positive linear correlation between mixture toxicity and pETH and pBPA, which indicated that ETH and BPA were the key components of the toxic effects. However, there was a significant negative linear correlation between the antagonism intensity and pBPA and pTBEP, which demonstrated that BPA and TBEP were the key components of the antagonism intensity. Pollutants and their mixtures can also damage cellular structures, and mixtures can exacerbate the dissolution of DNA and soluble proteins.

IDENTIFICATION OF CALAMANSI FRUIT PEEL ESSENTIAL OIL COMPONENTS FROM BENGKULU USING GC-MS

Calamansi orange (Citrofortunella microcarpa) is one of the citrus groups that have been cultivated in Bengkulu Province. Calamansi oranges have a distinctive aroma from the volatile oil components found in the skin of the fruit. This study aimed to identify the components of Bengkulu calamansi peel essential oil using GC-MS. The essential oil of calamansi fruit peel was obtained by steam distillation method using vacuum distillation. The essential oil yield obtained was 0.36%. The results of the examination of essential oils using GC-MS showed that there were 6 main compounds. they are 3-carane, Cyclopentanone, 2-(-methyl propyl), Cychexanol, 2methyl-5-(1-methylethenyl), Decanal, L-alpha-Terpineol and D-Crvone.&#x0D; &#x0D;

Simultaneous microdetermination of different penicillin antibiotics residues for cross-contamination study in non-penicillin dosage forms

Cross-contamination of non-penicillin products with penicillin drugs can initiate life-threatening allergic hypersensitivity reactions, thus, all non-penicillin products should be tested for contamination before sale. This work describes a fast simple HPLC-DAD method for the simultaneous microdetermination of nine penicillin drugs for studying cross contamination of non-penicillin pharmaceutical dosage forms. Separation was done on C18 column with elution using 0.02 M phosphate buffer and methanol delivered in gradient mode and detection at 220 nm using DAD. Separation of all penicillins from non-penicillin drugs and their co-formulated excipients (methyl paraben, propyl paraben, sorbitol and sodium benzoate) with acceptable suitability parameters was obtained. The linearity ranges were within the range of 0.5–100 µg·mL−1 with good accuracy (Er% between −0.24 and 0.21 %) and precision (RSD% between 0.47 and 0.71 %). Good sensitivity was indicated by the obtained low limits of detection (0.1–1 µg·mL−1) for all the studied compounds. Successful application of the developed method in studying cross contamination of different non-penicillin products including salbutamol syrup and respiratory solution, miconazole cream, biperiden tablet, formoterol inhaler capsule and omeprazole capsule with residues of 9 penicillin drugs was performed without interference from all adjuvants. Henceforth, the proposed method can be recommended for the routine quality control to study and determine cross contamination of the non-penicillin facility with trace amounts of any of the studied penicillins with high accuracy and precision.