Magnetic molecularly imprinted polymer nanoparticles for the extraction and clean-up of thiamethoxam and thiacloprid in light and dark honey.

In this work, new selective and sensitive dual-template molecularly imprinted polymer nanoparticles (MIPs) were synthesized and characterized. Sorbent MIPs were investigated for simultaneous extraction and clean-up of thiamethoxam and thiacloprid from light and dark honey samples. In this study, ultra-high-performance liquid chromatography-tandem mass spectrometry triple-quadrupole (UHPLC-MS/MS) (QQQ) was used to detect and quantify the pesticides. The kinetic model with adsorption kinetics of sorbent was investigated. The optimal adsorption conditions were 80 mg of polymer MIPs, a 30-min extraction time, and a pH of 7. The detection limit (LOD) and the quantification limit (LOQ) varied from 0.045 to 0.070 µg kg-1 and from 0.07 to 0.10 µg kg-1, respectively. The intra-day and inter-day precision (RSD, %) ranged from 1.3 to 2.0% and from 8.2 to 12.0%, respectively. The recovery of thiamethoxam and thiacloprid ranged from 96.8 to 106.5% and 95.3 to 104.4%, respectively, in light and dark honey samples.

Removing acesulfame with the peroxone process: Transformation products, pathways and toxicity.

Emerging contaminants (ECs) are receiving considerable attention because of their widespread occurrence, persistence and potential threat to the environment, wildlife and humans. Acesulfame (ACE), an extensively used artificial sweetener, is the most worrisome example of ECs. The photolysis/photocatalysis, chlorination and/or permanganate oxidation of ACE produces transformation products (TPs) that are more persistent and toxic than precursors. Thus, an alternative treatment method to treat ACE is required; oxidation by the peroxone process could be that method and was systematically investigated, as reported here. During the peroxone process, ACE degradation followed pseudo-first-order kinetics, with a rate that was significantly higher than after conventional ozonation. The hydroxyl radical was the major reactive species. Amount of hydrogen peroxide (H2O2) used, pH and type of water matrix showed significant influence on ACE degradation. Fifteen TPs in ultrapure water extracts, including four newly reported compounds, were identified and characterized by high resolution mass spectrometry (HR-MS) based on accurate mass measurements and MS/MS fragmentation. The reduced toxicity compared to other reported treatments of ACE was likely due to different transformation pathways and TPs generated. The peroxone process therefore appears to be one viable choice for safe removal of ACE.

A Rapid Dialysis Method for Analysis of Artificial Sweeteners in Foods (2nd Report).

Following the previous report, a rapid dialysis method was developed for the extraction and purification of four artificial sweeteners, namely, sodium saccharide (Sa), acesulfame potassium (AK), aspartame (APM), and dulcin (Du), which are present in various foods. The method was evaluated by the addition of 0.02 g/kg of these sweeteners to a cookie sample, in the same manner as in the previous report. Revisions from the previous method were: reduction of the total dialysis volume from 200 to 100 mL, change of tube length from 55 to 50 cm, change of dialysate from 0.01 mol/L hydrochloric aqueous solution containing 10% sodium chloride to 30% methanol solution, and change of dialysis conditions from ambient temperature with occasional shaking to 50℃ with shaking at 160 rpm. As a result of these revisions, the recovery reached 99.3-103.8% with one hour dialysis. The obtained recovery yields were comparable to the recovery yields in the previous method with four hour dialysis.

Determination of Meloxicam in Egg Whites and Yolks Using Reverse Phase Chromatography.

A new method of analysis has been developed and validated for the determination of meloxicam in egg whites and yolks. Following a liquid extraction for the whites and a solid phase extraction for the yolks, samples were separated on an XBridge C18 column and quantified using ultraviolet detection at 360 nm. The mobile phase was a mixture of water with glacial acetic acid and acetonitrile, with a flow rate of 1 mL/min. The procedure produced a linear graph over the concentration range 5-1500 ng/mL with a lower limit of quantification of 5 ng/mL. Intra- and inter-assay variability was 10% or less for both the whites and yolks. The average recovery for whites was 96% and the average recovery in yolks was 97%.

Two new compounds from Xanthium strumarium.

One new lignan, fructusol A (1), and one new thiazine derivative, 2-hydroxy-xanthiazone (2), along with eight known ones, were isolated from the seeds of Xanthium strumarium. The structures of new compounds were elucidated on the basis of extensive spectroscopic methods. Meanwhile, compounds 1-3 were tested for their antifungal activities against Candida albicans (ATCC 10231) in vitro. No one showed obvious inhibitions (MIC90 > 128 µg/ml).

Ion-exchange molecularly imprinted polymer for the extraction of negatively charged acesulfame from wastewater samples.

Acesulfame is a known indicator that is used to identify the introduction of domestic wastewater into water systems. It is negatively charged and highly water-soluble at environmental pH values. In this study, a molecularly imprinted polymer (MIP) was synthesized for negatively charged acesulfame and successfully applied for the selective solid phase extraction (SPE) of acesulfame from influent and effluent wastewater samples. (Vinylbenzyl)trimethylammonium chloride (VBTA) was used as a novel phase transfer reagent, which enhanced the solubility of negatively charged acesulfame in the organic solvent (porogen) and served as a functional monomer in MIP synthesis. Different molecularly imprinted polymers were synthesized to optimize the extraction capability of acesulfame. The different materials were evaluated using equilibrium rebinding experiments, selectivity experiments and scanning electron microscopy (SEM). The most efficient MIP was used in a molecularly imprinted-solid phase extraction (MISPE) protocol to extract acesulfame from wastewater samples. Using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analysis, detection and quantification limits were achieved at 0.12µgL(-1) and 0.35µgL(-1), respectively. Certain cross selectivity for the chemical compounds containing negatively charged sulfonamide functional group was observed during selectivity experiments.

Thiasporines A-C, thiazine and thiazole derivatives from a marine-derived Actinomycetospora chlora.

Thiasporine A (1), the first natural product with a 5-hydroxy-4H-1,3-thiazin-4-one moiety, along with two new thiazole derivatives, thiasporines B and C (2 and 3), were isolated from the marine-derived Actinomycetospora chlora SNC-032. The structures of 1-3 were established on the basis of comprehensive spectroscopic analysis and chemical methods. Thiasporine A showed cytotoxicity against the non-small-cell lung cancer cell line H2122 with an IC50 value of 5.4 µM.

[A rapid dialysis method for analysis of artificial sweeteners in food].

A simple and rapid dialysis method was developed for the extraction and purification of four artificial sweeteners, namely, sodium saccharin (Sa), acesulfame potassium (AK), aspartame (APM), and dulcin (Du), which are present in various foods. Conventional dialysis uses a membrane dialysis tube approximately 15 cm in length and is carried out over many hours owing to the small membrane area and owing to inefficient mixing. In particular, processed cereal products such as cookies required treatment for 48 hours to obtain satisfactory recovery of the compounds. By increasing the tube length to 55 cm and introducing efficient mixing by inversion at half-hour intervals, the dialysis times of the four artificial sweeteners, spiked at 0.1 g/kg in the cookie, were shortened to 4 hours. Recovery yields of 88.9-103.2% were obtained by using the improved method, whereas recovery yields were low (65.5-82.0%) by the conventional method. Recovery yields (%) of Sa, AK, APM, and Du, spiked at 0.1 g/kg in various foods, were 91.6-100.1, 93.9-100.1, 86.7-100.0 and 88.7-104.7 using the improved method.

Enrichment of neonicotinoid insecticides from lemon juice sample with magnetic three-dimensional graphene as the adsorbent followed by determination with high-performance liquid chromatography.

A novel 3D-graphene (3D-G) magnetic nanomaterial was prepared and used as an adsorbent for the extraction of four neonicotinoid insecticides (acetamiprid, imidacloprid, thiacloprid, and thiamethoxam) from lemon juice sample. Then, HPLC with UV detection was applied for the determination of the neonicotinoid insecticides desorbed from the 3D-G magnetic nanomaterial. The main experimental parameters that affect the extraction efficiencies such as the amount of 3D-G magnetic nanomaterial, sample solution pH, extraction time, salting-out effect, and desorption conditions were studied and optimized. As a result, the linear concentration range of the method was from 0.3 to 100.0 ng/mL for thiacloprid, from 0.5 to 100.0 ng/mL for imidacloprid and acetamiprid, and from 1.0 to 100.0 ng/mL for thiamethoxam, with correlation coefficients of 0.9965-0.9985, respectively. The LODs of the method based on an S/N of 3 were between 0.08 and 0.2 ng/mL. The enrichment factors obtained were between 67 and 427, and the RSDs (n = 6) were in the range from 4.6 to 7.1%, and the recoveries of the method fell in the range of 88.75 to 111.60%.

Enantiomeric separation and simulation studies of pheniramine, oxybutynin, cetirizine, and brinzolamide chiral drugs on amylose-based columns.

Solid phase extraction (SPE)-chiral separation of the important drugs pheniramine, oxybutynin, cetirizine, and brinzolamide was achieved on the C18 cartridge and AmyCoat (150 x 46 mm) and Chiralpak AD (25 cm x 0.46 cm id) chiral columns in human plasma. Pheniramine, oxybutynin, cetirizine, and brinzolamide were resolved using n-hexane-2-PrOH-DEA (85:15:0.1, v/v), n-hexane-2-PrOH-DEA (80:20:0.1, v/v), n-hexane-2-PrOH-DEA (70:30:0.2, v/v), and n-hexane-2-propanol (90:10, v/v) as mobile phases. The separation was carried out at 25 ± 1 ºC temperature with detection at 225 nm for cetirizine and oxybutynin and 220 nm for pheniramine and brinzolamide. The flow rates of the mobile phases were 0.5 mL min(-1). The retention factors of pheniramine, oxybutynin, cetirizine and brinzolamide were 3.25 and 4.34, 4.76 and 5.64, 6.10 and 6.60, and 1.64 and 2.01, respectively. The separation factors of these drugs were 1.33, 1.18, 1.09 and 1.20 while their resolutions factors were 1.09, 1.45, 1.63 and 1.25, and 1.15, respectively. The absolute configurations of the eluted enantiomers of the reported drugs were determined by simulation studies. It was observed that the order of enantiomers elution of the reported drugs was S-pheniramine > R-pheniramine; R-oxybutynin > S-oxybutynin; S-cetirizine > R-cetirizine; and S-brinzolamide > R-brinzolamide. The mechanism of separation was also determined at the supramolecular level by considering interactions and modeling results. The reported SPE-chiral high-performance liquid chromatography (HPLC) methods are suitable for the enantiomeric analyses of these drugs in any biological sample. In addition, simulation studies may be used to determine the absolute configuration of the first and second eluted enantiomers.

Determination of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone by liquid chromatography-tandem mass spectrometry.

2-(3-Benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitor, is newly developed for the control of type 2 diabetes mellitus (T2DM) and metabolic syndrome. A method for the determination of KR-66344 in rat plasma was developed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) to evaluate the pharmacokinetics of KR-66344. Plasma samples were processed by a liquid-liquid extraction method with ethyl acetate and introduced onto the LC-MS-MS system. The analyte and imipramine (internal standard) were analyzed by multiple reaction monitoring based on transitions at m/z 420.1 → 105.0 and 282.2 → 86.0, respectively. The calibration curve was linear (r = 0.9993) over the concentration range of 1.0-1,000 ng/mL. The mean recovery values for KR-66344 and imipramine were 83.8 and 86.2%, respectively. The mean inter-day and intra-day assay precision values were 3.9 and 2.4%, respectively. KR-66344 was stable under various handling and storage conditions. This developed method was applied to a pharmacokinetic study after the oral administration of KR-66344 in rats. The concentration of KR-66344 was readily measurable in rat plasma up to 24 h post-dose after an oral administration, suggesting that current assay is applicable to pharmacokinetic studies for KR-66344.

Occurrence and fate of the angiotensin II receptor antagonist transformation product valsartan acid in the water cycle--a comparative study with selected ß-blockers and the persistent anthropogenic wastewater indicators carbamazepine and acesulfame.

The substantial transformation of the angiotensin II receptor antagonist valsartan to the transformation product 2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-carboxylic acid (referred to as valsartan acid) during the activated sludge process was demonstrated in the literature and confirmed in the here presented study. However, there was a severe lack of knowledge regarding the occurrence and fate of this compound in surface water and its behavior during drinking water treatment. In this work a comparative study on the occurrence and persistency of valsartan acid, three frequently used ß-blockers (metoprolol, atenolol, and sotalol), atenolol acid (one significant transformation product of atenolol and metoprolol), and the two widely distributed persistent anthropogenic wastewater indicators carbamazepine and acesulfame in raw sewage, treated wastewater, surface water, groundwater, and tap water is presented. Median concentrations of valsartan acid in the analyzed matrices were 101, 1,310, 69, <1.0, and 65 ng L(-1), respectively. Treated effluents from wastewater treatment plants were confirmed as significant source. Regarding concentration levels of pharmaceutical residues in surface waters valsartan acid was found just as relevant as the analyzed ß-blockers and the anticonvulsant carbamazepine. Regarding its persistency in surface waters it was comparable to carbamazepine and acesulfame. Furthermore, removal of valsartan acid during bank filtration was poor, which demonstrated the relevance of this compound for drinking water suppliers. Regarding drinking water treatment (Muelheim Process) the compound was resistant to ozonation but effectively eliminated (≥90%) by subsequent activated carbon filtration. However, without applying activated carbon filtration the compound may enter the drinking water distribution system as it was demonstrated for Berlin tap water.

Dispersive liquid-liquid microextraction combined with sweeping micellar electrokinetic chromatography for the determination of some neonicotinoid insecticides in cucumber samples.

A rapid, simple and sensitive method has been developed for the analysis of some neonicotinoid insecticides in cucumber samples by using dispersive liquid-liquid microextraction (DLLME) coupled with sweeping in micellar electrokinetic chromatography (MEKC). Under optimised conditions, the enrichment factors were achieved in the range from 4000 to 10,000. The linearity of the method was in the range from 2.7 to 200 ng g(-1) for thiacloprid, acetamiprid and imidacloprid, and in the range from 4.0 to 200 ng g(-1) for imidaclothiz in cucumber samples, with the determination coefficients (r(2)) ranging from 0.9924 to 0.9968. The limits of detection (LODs, S/N=3) ranged from 0.8 to 1.2 ng g(-1). The relative standard deviations (RSDs) at the concentration levels of 10.0 and 50.0 ng g(-1) each of the neonicotinoid insecticides in cucumber samples varied from 3.8% to 6.3%. The developed method has been successfully applied to the analysis of the neonicotinoid insecticides in cucumbers with a satisfactory result.

Cytotoxic pheofungins from an engineered fungus impaired in posttranslational protein modification.

What makes a fungus blush? The deletion of a gene that is required for global protein N-acetylation triggers the production of unprecedented metabolites in Aspergillus nidulans. The pronounced red pigmentation of the engineered mutant is caused by pheofungins (benzothiazinone chromophores), the biogenesis of which is strikingly similar to those of pheomelanins found in red bird feathers and hair of Celtic origin.

Inhibitory effects of 1,3-thiazine derivatives on melanogenesis.

OBJECTIVES: The aim of this study was to identify a novel skin-depigmenting agent from synthetic 1,3-thiazine derivatives. METHODS: We investigated the inhibitory effects of six kinds of 1,3-thiazine derivative on melanogenesis by examining their effects on tyrosinase activity and melanin biosynthesis in melan-a cells and the zebrafish model. KEY FINDINGS: Of the six compounds, 4-hydroxy-2,6-dimethyl-5,6-dihydro-4H-1,3-thiazine (TZ-6) had the strongest anti-melanogenic effects in cultured melan-a cells (30.4% inhibition at 100 microm). In addition, TZ-6 exhibited an inhibitory effect on mushroom and cellular tyrosinase. Based on the results of Western blotting, TZ-6 reduced the expression of tyrosinase at 100 microm. Additionally, TZ-6 reduced body pigmentation and inhibited tyrosinase activity in the zebrafish model. CONCLUSIONS: The results have provided useful information for the development of a skin whitening agent.

A new thiaziedione from the fruits of Xanthium sibiricum.

A novel sulphur-containing compound named xanthiazinone (1) was isolated from the ethanolic extract of the fruits of Xanthium sibiricum, along with four known compounds, xanthiazone (2), xanthiside (3), xanthienopyran (4) and 5-hydroxypyrrolidin-2-one (5). Their structures were determined on the basis of spectroscopic techniques.

Anti-inflammatory thiazine alkaloids isolated from the New Zealand ascidian Aplidium sp.: inhibitors of the neutrophil respiratory burst in a model of gouty arthritis.

Ascidiathiazones A (3) and B (4), two new tricyclic thiazine-containing quinolinequinone alkaloids, were isolated from the New Zealand ascidian Aplidium species. Both compounds inhibited the in vitro production of superoxide by PMA-stimulated human neutrophils in a dose-dependent manner with IC50 1.55 +/- 0.32 and 0.44 +/- 0.09 microM, respectively. In vivo inhibition of superoxide production by peritoneal neutrophils in a murine model of gout was observed for both compounds with oral doses of 25.6 micromol/kg. Ascidiathiazone A (3) was synthesized in four steps from 8-hydroxyquinoline-2-carboxylic acid.

A new thiazinedione from Xanthium strumarium.

A new thiazinedione was isolated from the fruit of Xanthium strumarium. Its structure was elucidated by a combination of spectral methods.

Separation and simultaneous determination of four artificial sweeteners in food and beverages by ion chromatography.

In this paper, the separation and determination of four artificial sweeteners (aspartame, sodium cyclamate, acesulfame-K and sodium saccharin) by ion chromatography coupled with suppressed conductivity detector is reported. The four artificial sweeteners were separated using KOH eluent generator. Due to the use of eluent generator, very low conductance background conductivity can be obtained and sensitivity of sweeteners has been greatly improved. Under the experimental condition, several inorganic anions, such as F-, Cl-, NO3-, NO2-, Br-, SO4(2)-, PO4(3)- and some organic acid such as formate, acetate, benzoate, and citrate did not interfere with the determination. With this method, good linear relationship, sensitivity and reproducibility were obtained. Detection limits of aspartame, sodium cyclamate, acesulfame-K, sodium saccharin were 0.87, 0.032, 0.019, 0.045 mg/L, respectively. Rate of recovery were between 98.23 and 105.42%, 99.48 and 103.57%, 97.96 and 103.23%, 98.46 and 102.40%, respectively. The method has successfully applied to the determination of the four sweeteners in drinks and preserved fruits.

A new heterocyclic glucoside from the fruits of Xanthium pungens.

A new thiazinedione glucoside, 7-(beta-D-glucopyranosyloxymethyl)-8,8-dimethyl-4,8-dihydrobenzo[1,4]thiazine-3,5-dione (1) and named xanthiside, was isolated from the methanol extract of the fruits of Xanthium pungens. Its structure was determined by spectroscopic techniques including, IR, CIMS, high-resolution-EIMS, and extensive 400 MHz one- and two-dimensional NMR-analysis (1H, 13C-NMR, DEPT, 1H-1H COSY, HMQC, COLOC, and NOE experiments).