Low-toxicity Solvent Research Articles

Liquid Chromatographic Determination of NSAIDs in Urine After Dispersive Liquid–Liquid Microextraction Based on Solidification of Floating Organic Droplets

An environmentally benign method of sample preparation based on dispersive liquid–liquid microextraction and solidification of floating organic droplets (DLLME-SFO) coupled with high-performance liquid chromatography with ultraviolet detection has been developed for analysis of non-steroidal anti-inflammatory drugs (NSAIDs) in biological fluids. A low-toxicity solvent was used to replace the chlorinated solvents commonly used in conventional DLLME. Seven conditions were investigated and optimized: type and volume of extraction solvent and dispersive solvent, extraction time, effect of addition of salt, and sample pH. Under the optimum conditions, good linearity was obtained in the range 0.01–10 µg mL−1, with coefficients of determination (r2) >0.9949. Detection limits were in the range 0.0034–0.0052 µg mL−1 with good reproducibility (RSD) and satisfactory inter-day and intra-day recovery (95.7–115.6 %). The method was successfully used for analysis of diclofenac, mefenamic acid, and ketoprofen in human urine. Analysis of urine samples from a patient 2 and 4 h after administration of diclofenac revealed concentrations of 1.20 and 0.34 µg mL−1, respectively.

Preparation of Uniform Poly (Acrylamide-co-DVB) Microspheres in a Low Toxicity Solvent by Dispersion Polymerization

Uniform poly (acrylamide-co-DVB) microspheres (DVB = divinylbenzene) with number-average diameter varying from 1.65 to 2.86 µm and polydispersity index from 1.011 to 1.176 were prepared in a low toxicity solvent, i.e. ethanol/water mixtures, by dispersion polymerization using octylphenol polyoxyethylene (10) ether as the stabilizer and 2,2′-azobisisobutyronitrile as the initiator. The parameters, such as solvent composition, initiator concentration, and monomer composition, which influence both the product yield and morphology, were investigated by gravimetry and scanning electron microscopy. The results indicate that for the formation of uniform microspheres, there exists a threshold for each parameter. At the maximum threshold, blobs would apparently appear on the surface of the microspheres. Below or above the thresholds would result in doublet- or triplet-shaped particles, flocs, or a mixture of both. The yield of the uniform microspheres could be up to ~35 % by changing the parameters moderately within the threshold range.

A new method for lipid extraction using low-toxicity solvents developed for canola (Brassica napus L.) and soybean (Glycine max L. Merrill) seeds

A fast, easy lipid extraction method using low-toxicity solvents is developed in this study for oilseed samples rich in polyunsaturated fatty acid.

UHPLC-MS/MS assay using environment friendly organic solvents: A green approach for fast determination of quetiapine in rat plasma

Reduction or elimination of traditional hazardous chemicals in chromatographic separation and sample preparation is comparatively safer and can be considered as a greener approach for the determination of analytes in biological matrices. A rapid and sensitive UHPLC-MS/MS assay for determination of quetiapine in rat plasma was developed and validated using environment friendly and low toxic organic solvents as organic modifier in mobile phase and sample preparation. Quetiapine and risperidone (internal standard) were separated on Acquity BEH™ C18 column (50×2.1mm, i.d. 1.7μm) using ethanol–water-formic acid (80:20:0.1, v/v/v) as mobile phase at a flow rate of 0.3mL/min. Detection was performed on tandem mass spectrometer using positive electrospray ionization source by multiple reaction monitoring mode. The precursor to product ion transitions of m/z 384.13>253.00 for quetiapine and m/z 411.18>191.07 for IS was used to quantify them respectively. The method was found to be linear in the concentration range of 0.45–500ng/mL. All validation parameters were within acceptable range, as defined by guidelines of bio-analytical method validation. In conclusion, bioanalytical assay using UHPLC-MS/MS together with environment friendly and low toxic organic solvents in mobile phase and sample preparation may be considered as greener approach for quantification of analytes in plasma samples.

The Structure and Properties of Lysine Doped Polypeptide Modified Polypyrrole Nanoparticles

Lysine doped polypeptide modified particles were chemically synthesized in different weight ratios of polypeptide to Py feed. The microstructures of these PPys were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier Transform Infrared (FTIR). Semiconductor parameter analyzer, ubbelohde viscometer and rotation viscometer were used to characterize the electrical property, viscosity and solubility of these PPys. The results show that the polypeptide has the function as the template in the Py polymerization. The lysine doped PPys form many rings with diameters of about several micrometers, with the weight ratio increase, the ring structure become more obvious and the diameters of the rings decrease to about 200 nm. The conductivity of lysine doped polypeptide modified PPys synthesized with the weight ratio of 3:1 is about 1.73 × 10-3S/cm. It is mostly soluble in acetic acid, good soluble in the mixture of acetic acid and HFIP with a volume ratio of 2:1. Moreover, the solubility in the mixture of acetic acid and HFIP is little affected by weight ratio and maintain about 93.8%, indicating its good solubility in no toxicity solvent or very low toxicity solvent.

Ultrasound-assisted emulsification magnetic microextraction: a fast and green method for the determination of triazole fungicides in fruit juice

A fast microextraction technique, termed as ultrasound-assisted emulsification magnetic microextraction, was developed for the determination of triazole fungicides (penconazole, tebuconazole and myclobutanil) in fruit juice samples by gas chromatography flame ionization detection. The distinct advantage of the proposed method is that a low toxic solvent, 1-octanol, is used as an extractant, without using a disperser. With the help of ultrasound, emulsification can be obtained. Magnetic nanoparticles are applied to retrieve the extractant, replacing centrifugation. Under optimal conditions, good linearity in the range of 5 μg L−1 to 500 μg L−1, repeatability (RSD 3.5–7.7%), low LODs (1.8–2.3 μg L−1) and good recovery (85.4–105%) were obtained. Additionally, the intermolecular binding energies were theoretically studied using density functional theory and the explicit solvent molecule model. A high correlation was found among the extraction efficiency, Kow and the calculated energies, which may guide the application of extractants and the selectivity of the target analytes in analytical methods.

Nano BF3·SiO2: A green heterogeneous solid acid for synthesis of formazan dyes under solvent-free condition

A solvent-free, efficient and rapid approach for synthesis of formazan dyes was developed by diazotization of aromatic amines with NaNO2, nano silica-supported boron trifluoride (nano BF3·SiO2), then diazo coupling with aldehyde phenylhydrazones by grinding method at room temperature. This study aimed to overcome the limitations and drawbacks of the previous reported methods such as: low temperature, using corrosive and toxic acids and solvents, using buffer solutions, instability of aryl diazonium salts, modest yields, and long reaction times.

Surface Selective One-Step Fabrication of Carbon Nanotube Thin Films with High Density

Thin films of carbon nanotubes (CNTs) are fabricated from solution using a one-step directed assembly strategy. Very high surface selectivity and exceptionally high CNT densities can be observed in small features with complex shapes. This directed assembly technique makes use of minimum amounts of CNTs and low toxicity solvents, and can be applied to metallic, semiconducting and mixed CNTs for fabrication of thin films over macroscopic areas. The thin films obtained with this approach are used for thin-film transistor (TFT) fabrication, and their electrical characterization is described.

Low Toxic Organic Solvent-Based Ultrasound-Assisted Emulsification Microextraction for the Residue Analysis of Benzimidazole Anthelmintics in Egg Samples by High Performance Liquid Chromatography

Preconcentration and determination of benzimidazole anthelmintics in egg samples has been successfully carried out using low-toxic organic solvent based ultrasound-assisted emulsification microextraction (UAEME) method coupled with high performance liquid chromatography (HPLC). A modified quick, easy, cheap, effective, rugged and safe (QuEChERS) was used for precipitating protein and fat in egg samples before subjecting it to UAEME–HPLC. In UAEME, 1-octanol was used as extraction solvent and MeOH (chosen disperser solvent) under ultrasound radiation assisted. Under the optimum condition chosen (60 μl of octanol, 250 μl of MeOH, and 4-min ultrasonication), extraction efficiency was obtained in the range of 30–95, depending on the analytes. Limits of detection (LODs) of the studied benzimidazoles in egg samples were 7.2–14.4 μg/kg. Satisfied recoveries evaluated at the four-level spiked concentrations (i.e., 25, 50, 100, and 150 μg/kg) were obtained between 74.3 and 112.9 with the relative standard deviation (RSD) less than 11.5 %. Precisions comprising intra-day and inter-day measurements were obtained with RSD below 9.0 %. Less consumption of low toxic organic solvents, simple, and effective are beneficial of the demonstrated method.

Vortex-assisted surfactant-enhanced-emulsification liquid–liquid microextraction with solidification of floating organic droplet combined with HPLC for the determination of neonicotinoid pesticides

A microextraction procedure based on vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction with solidification of floating organic droplet (VSLLME-SFO) for preconcentration of neonicotinoid pesticides, including acetamiprid, clotianidin, nitenpyram, imidacloprid, and thiamethoxam, has been developed. In VSLLME-SFO process, the addition of surfactant (as an emulsifier), could be enhance the mass-transfer from the aqueous solution into the extraction solvent. The extraction solvent could be dispersed into the aqueous by vortex process. Other experimental parameters affected the extraction efficiency, including the kind and concentration of salt, concentration and volume of HCl, kind and concentration of surfactant and its volume, kind and volume of extraction solvent, vortex time and the centrifugation extraction time, were also optimized. The optimum extraction conditions of VSLLME-SFO were 10.00 mL of sample, 0.3% (w/v) Na2SO4, 50 µL of 0.050 mol L(-1) SDS, 1.0 mol L(-1) HCl (400 µL), 150 µL of octanol, vortex time 1 min and centrifugation time 10 min. The sediment phase was analyzed by subjecting it to HPLC using a mobile phase of 25% acetonitrile in water, at a flow rate of 1.0 mL min(-1), and photodiode array detection at 254 nm. Under the optimum extraction conditions, high enrichment factors (20-100 fold) and low limit of detection (0.1-0.5 μg L(-1)) could be obtained. This method provided high sensitivity, low toxic organic solvents used, and simplicity of the extraction processes. The proposed method was successfully applied in the analysis of neonicotinoids in fruit juice and water samples.

Magnetic Stirring-Assisted Dispersive Suspended Microextraction with Solidification of a Floating Organic Droplet for the Determination of Trace Fungicides in Water and Wine

For the first time, a simple method for magnetic stirring-assisted dispersive suspended microextraction has been developed for the determination of three fungicides (azoxystrobin, diethofencarb, and pyrimethanil) in water and wine samples. The method is based on the solidification of a floating organic droplet coupled with high performance liquid chromatography. In the proposed method, the low toxicity solvent 1-dodecanol was used as the extractant. Both the extraction and phase separation process were performed with magnetic stirring. No centrifugation step was involved. After separating the two phases, the extraction solvent droplet was easily collected through solidification at lower temperature. Important parameters such as the kind and volume of organic extraction solvent, extraction and restoration speed, extraction and restoration time, and salt concentration were optimized. Under the optimal conditions, the limits of detection for the analytes varied from 0.14 to 0.26 µg L−1. The enrichment factors ranged from 125–200. The linearity ranges were 1–2000 µg L−1, yielding correlation coefficients (r) higher than 0.9990. The relative standard deviation (n = 6) at two spiked level of 0.2 µg mL−1 and 4 µg L−1 varied between 2.2% and 7.8%. Finally, the developed technique was successfully applied to determine target fungicides in real water and wine samples, where the obtained recoveries ranged from 83.8–105.3%

Comparison of Eleven Extraction Methods for Quantitative Evaluation of Total Lipids and Fatty Acids in the ClamAnadara inaequivalvis(Bruguière)

The clam Anadara inaequivalvis (Bruguière) is a bivalve mollusc now populating several areas of the Mediterranean Sea seafloor where it competes with other molluscs harvested as food. In fact, even though Anadara inaequivalvis has valuable nutritional properties, it has no commercial value in European countries. The aim of this study was to evaluate quantitatively and qualitatively fatty acid content in this bivalve mollusc and to compare 11 extraction methods: conventional procedures such as Folch, Bligh and Dyer, and Soxhlet with different solvents, as well as accelerated solvent extraction (ASE) and methods using low-toxicity solvents as substitutes for chloroform (CHCl3) and methanol (MeOH). The best method was ASE CHCl3-MeOH, affording yields of total lipids, total fatty acids, and polyunsaturated fatty acids (PUFAs) significantly higher than any other method. The estimated range of total lipids was 2.29%–6.99% (on the dry sample), and the range of fatty acids was 0.74%–1.78%. Yields of polyunsaturated fatty acids (PUFAs) ranged from 0.10% to 0.40%. The solvent mixture hexane—isopropanol as substitute for CHCl3-MeOH did not afford good results. PUFAs were 22.5% in the total fatty acids and the ratio between PUFAs n-3 and PUFA n-6 was 2.74:1.

Simultaneous derivatization and extraction of chlorophenols in water samples with up-and-down shaker-assisted dispersive liquid–liquid microextraction coupled with gas chromatography/mass spectrometric detection

A new up-and-down shaker-assisted dispersive liquid-liquid microextraction (UDSA-DLLME) for extraction and derivatization of five chlorophenols (4-chlorophenol, 4-chloro-2-methylphenol, 2,4-dichlorophenol, 2,4,6-trichloro-phenol, and pentachlorophenol) has been developed. The method requires minimal solvent usage. The relatively polar, water-soluble, and low-toxicity solvent 1-heptanol (12 μL) was selected as the extraction solvent and acetic anhydride (50 μL) as the derivatization reagent. With the use of an up-and-down shaker, the emulsification of aqueous samples was formed homogeneously and quickly. The derivatization and extraction of chlorophenols were completed simultaneously in 1 min. The common requirement of disperser solvent in DLLME could be avoided. After optimization, the linear range covered over two orders of magnitude, and the coefficient of determination (r (2)) was greater than 0.9981. The detection limit was from 0.05 to 0.2 μg L(-1), and the relative standard deviation was from 4.6 to 10.8 %. Real samples of river water and lake water had relative recoveries from 90.3 to 117.3 %. Other emulsification methods such as vortex-assisted, ultrasound-assisted, and manual shaking-enhanced ultrasound-assisted methods were also compared with the proposed UDSA-DLLME. The results revealed that UDSA-DLLME performed with higher extraction efficiency and precision compared with the other methods.

Micellar Electrokinetic Chromatography Method for Determination of the Ten Water-Soluble Vitamins in Food Supplements

The separation and determination of the ten water-soluble vitamins by using capillary electrophoresis in the micellar electrokinetic chromatography in a single run are proposed. The method uses low toxicity and cost solvent (ethanol) as modifier of background electrolyte (BGE) attending to the Green Chemistry principles. The electrophoretic method uses 10.0 % (v/v) ethanol, 2.0 % (w/v) SDS, 0.02 mol L−1 borate at pH 8.70 as BGE. The standard and real sample solutions were injected in the eletrophoretic system by hydrodynamic injection under pressure of 0.80 psi for 8 s, and the separation was carried out in a fused silica capillary under a potential of 28 kV at 25 °C; the analytical signals were monitored at 214 nm. The analytical method is precise (r.s.d. < 6 %), accurate (better than 9 %), selective, sensitive, robust, simple, and presents high analytical frequency as ten water-soluble vitamins were separated in only 18 min, with migration times of 5.75 ± 0.02, 6.81 ± 0.02, 8.13 ± 0.04, 8.80 ± 0.07, 8.98 ± 0.06, 11.10 ± 0.08, 11.34 ± 0.05, 13.85 ± 0.15, 14.82 ± 0.04, and 17.85 ± 0.30 min. Detection and quantification limits of 0.34, 0.32, 0.27, 0.20, 2.50, 4.98, 4.92, 0.30, 0.86 and 0.28 mg L−1 and 1.02, 0.97, 0.83, 0.62, 7.56, 15.09, 14.91, 0.90, 2.59 and 0.83 mg L−1, for vitamins PP (nicotinamide), B12 (cyanocobalamin), B2 (riboflavin), B6 (pyridoxine), B8 (biotin), C (ascorbic acid), B5 (pantothenic acid), B3 (nicotinic acid), B1 (thiamine), and B9 (folic acid), respectively. Excellent recoveries (intra and inter-day) were obtained and, when the method was applied to food supplement analyses the results were in agreement with the conventional HPLC methods.

Ultrasound-assisted surfactant-enhanced emulsification microextraction based on the solidification of a floating organic droplet used for the simultaneous determination of six fungicide residues in juices and red wine

A novel ultrasound-assisted surfactant-enhanced emulsification microextraction technique based on the solidification of a floating organic droplet followed by high performance liquid chromatography with diode array detection was developed for simultaneous determination of six fungicide residues in juices and red wine samples. The low-toxicity solvent, 1-dodecanol, was used as an extraction solvent. For its low density and proper melting point near room temperature, the extractant droplet was collected easily by solidifying it at a low temperature. The surfactant, Tween 80, was used as an emulsifier to enhance the dispersion of the water-immiscible extraction solvent into an aqueous phase, which hastened the mass-transfer of the analytes. Organic dispersive solvent typically required in common dispersive liquid–liquid microextraction methods was not used in the proposed method. Some parameters (e.g., the type and volume of extraction solvent, the type and concentration of surfactant, ultrasound extraction time, salt addition, and volume of samples) that affect the extraction efficiency were optimized. The proposed method showed a good linearity within the range of 5μgL−1–1000μgL−1, with the correlation coefficients (γ) higher than 0.9969. The limits of detection for the method ranged from 0.4μgL−1 to 1.4μgL−1. Further, this simple, practical, sensitive, and environmentally friendly method was successfully applied to determine the target fungicides in juice and red wine samples. The recoveries of the target fungicides in red wine and fruit juice samples were 79.5%–113.4%, with relative standard deviations that ranged from 0.4% to 12.3%.

A green protocol to prepare monodisperse poly(TMPTMA–styrene) microspheres by photoinitiated precipitation polymerization in low-toxicity solvent

To prepare monodisperse polymer microspheres under mild conditions, a green protocol is set up by means of photoinitiated precipitation polymerization. The work is carried out with three novel parameters, including: new type crosslinker of trifunctionality, low-toxicity solvent, and ambient temperature. Firstly, trihydroxymethyl propane triacrylate (TMPTMA) is selected as the most suitable crosslinker to prepare microspheres under ambient temperature, after comparing the morphology of its polymerization products with those of other two similar crosslinkers, i.e., trimethylolpropane triacrylate and ethoxylated trimethylolpropane triacrylate. In addition, as high as possible concentrations of TMPTMA and styrene are attempted to harvest the largest amounts of microspheres; however, a threshold of monomer concentration is found at 6 %. One kind of low-toxicity solvent, i.e., ethanol, is used as the reaction media to replace the commonly used toxic organic solvents, and it is proven to be the near Θ solvent for the present polymerization. Observation from scanning electron microscopy indicates that photoinitiation is an effective way to control the growth of microspheres, and highly monodisperse microspheres of 2.67 μm are achieved at polymerization time of 120 h. Finally, the reactive vinyl groups on microsphere surface are confirmed, which indicate that the microspheres from this green protocol is in favor of further functionalization and bio-medical application.

Preparation of porous microsphere-scaffolds by electrohydrodynamic forming and thermally induced phase separation

The availability of forming technologies able to mass produce porous polymeric microspheres with diameters ranging from 150 to 300μm is significant for some biomedical applications where tissue augmentation is required. Moreover, appropriate assembly of microspheres into scaffolds is an important challenge to enable direct usage of the as-formed structures in treatments. This work reports the production of poly (glycolic-co-lactic acid) and poly (ε-caprolactone) microspheres under ambient conditions using one-step electrohydrodynamic jetting (traditionally known as atomisation) and thermally induced phase separation (TIPS). To ensure robust production for practical uses, this work presents 12 comprehensive parametric mode mappings of the diameter distribution profiles of the microspheres obtained over a broad range of key processing parameters and correlating of this with the material parameters of 5 different polymer solutions of various concentrations. Poly (glycolic-co-lactic acid) (PLGA) in Dimethyl carbonate (DMC), a low toxicity solvent with moderate conductivity and low dielectric constant, generated microspheres within the targeted diameter range of 150–300μm. The fabrication of the microspheres suitable for formation of the scaffold structure is achieved by changing the collection method from distilled water to liquid nitrogen and lyophilisation in a freeze dryer.

Eco-solvents – cluster-formation, surfactantless microemulsions and facilitated hydrotropy

In this paper we consider clusters in the ternary systems water-benzyl alcohol and ethanol, ethyl lactate or γ-valerolactone as found with the help of dynamic and static light scattering experiments. These ternary mixtures are powerful solvent media and consist only of low-toxic solvents of natural origin. In a recent work we have shown that surfactantless microemulsions are formed in the water-ethanol-n-octanol system. By contrast, in the systems studied here the sizes of the aggregates are too small to be considered as micelles. It can be postulated that the presence of clusters or larger structures as in surfactantless microemulsions is strongly influenced by the most hydrophobic compound. The phenomenon of facilitated hydrotropy is also investigated in the above-mentioned systems. In this context, ethanol is considered as the primary hydrotrope and the more hydrophobic benzyl alcohol as the facilitating secondary hydrotrope. The hydrophobic dye Disperse Red 13 is used as a marker of facilitated hydrotropy. The results suggest that the degree of self-association of eco-solvent has a significant influence on the hydrotropic efficiency of benzyl alcohol.

ChemInform Abstract: Ionic Liquids: A New Strategy in Pharmaceutical Synthesis

AbstractReview: 33 refs.

Development and verification of sulforaphane extraction method in cabbage (Brassica oleracea L. var. capitata) and broccoli (Brassica oleracea L. var. italica Planch.)

A simple and repeatable method of extracting sulforaphane from cabbage and broccoli was developed and two inbred lines of broccoli with higher sulforaphane content in their seeds were found. The determination method was reverse-phase high performance liquid chromatography (RP-HPLC). In the extraction process, low toxic solvent ethyl acetate was applied for extraction of sulforaphane. The result showed that the linear equation was Y = 5907.07X + 4556.71, R2 = 0.9996 assistant with HPLC conditions, and there was a stable and repeatable HPLC condition with the recovery of 96.3% (n = 6, relative standard deviation (RSD) = 1.3%). The better hydrolysis conditions for sulforaphane generation were at pH 7.0, the ratio of buffer to materials (ml/g) 5 to 20:1 and reaction time 1.0 to 2.0 h at room temperature. Finally, eighteen cultivars of cabbage and twelve cultivars of broccoli were used for verification of sulforaphane exaction method. All the materials were proved that they all contained sulforaphane composition and two cultivars of broccoli were proved to contain higher sulforaphane in seeds than previous reports. Key words: Glucosinolate, sulforaphane, Brassica, broccoli, cabbage, reverse-phase high performance liquid chromatography (RP-HPLC)