Thermo-Assisted Deep Eutectic Solvent Based on Dispersive Liquid-Liquid Microextraction for Preconcentration of Phthalate Esters in Water Samples and Determination by Gas Chromatography With Flame Ionization Detection.

A thermo-assisted deep eutectic solvent (DES) based on dispersive liquid-liquid microextraction followed by gas chromatography with flame ionization detection was developed for the analysis of five phthalate esters in different water samples. In the procedure involved, a DES composed of lidocaine, an amphiphilic amine, and oleic acid, was mixed with the sample assisted by ultrasound, and phase separation was achieved with increasing temperature. The heating of the extraction system induced the change of acid-base properties of the DES components. Thus, the formation of microdroplets of DES in the sample was provided, and two phases were separated. The structure of the upper hydrophobic layer was characterized by Fourier-transform infrared spectroscopy. Also, the amount of water in the DES phase was analyzed by mass spectrometer and Karl Fischer titration. Some critical variables on the extraction yield were assessed. The proposed method achieved 1.2-1.3 and 4.1-4.3 µg/L for limits of detection and limits of quantification, respectively. The intra-day and inter-day percentage relative standard deviations (n = 5) were determined to be in the range of 4.2-6.2% and 5.1-7.2%, respectively. Ultimately, this method analyzed the five phthalate esters in different water samples with high recoveries.

Characterization of a Novel TiF4 Inclusion Complex and in vitro Evaluation of Its Effect on Inhibiting Enamel Demineralization.

INTRODUCTION: Titanium tetrafluoride (TiF4) is an anticariogenic agent with high remineralizing potential. However, the acidic pH of TiF4 solution can limit its clinical application. The present study aimed to prepare and characterize a new TiF4-dendrimer inclusion complex and evaluate its ability to inhibit enamel demineralization under pH cycling conditions. METHODS: PEG-citrate dendrimer and TiF4-dendrimer inclusion complex were synthesized and their molecular structures were evaluated using Fourier-transform Infrared Spectroscopy (FTIR), Hydrogen Nuclear Magnetic Resonance (HNMR), and Liquid Chromatography-Mass Spectrometry (LC-MS) tests. Forty-eight enamel samples were prepared and randomly divided into four groups: distilled water (negative control), TiF4 solution (T), dendrimer solution (D), and TiF4-dendrimer solution (TD). The microhardness of the samples was measured initially. Next, the samples underwent pH cycling, were exposed to the solutions, the microhardness was measured again, and microhardness loss was calculated. EDX analysis was performed on the surface and cross-sectional segments of the samples. RESULTS: The microhardness loss was significantly higher in control (-65.1 ± 6.0) compared to other groups. No significant difference was observed between T (-47.9 ± 5.6) and D (-41.7 ± 12.0) and also D and TD (-40.5 ± 9.4) in this regard. Microhardness loss was significantly higher in T compared to TD group. The TD samples showed similar fluoride and titanium content in both surface and subsurface regions, while the T group had higher concentrations in the surface region. Moreover, the TD solution had a higher pH of 3.4 compared to the T solution's pH of 1.1. CONCLUSION: No significant difference was observed between the efficacy of TiF4-dendrimer and TiF4 solution in inhibiting demineralization while TiF4-dendrimer solution had the added advantage of having a higher pH.

Separation and quantification of diazinon in water samples using liquid-phase microextraction-based effervescent tablet-assisted switchable solvent method coupled to gas chromatography-flame ionization detection.

This study used a liquid-phase microextraction-based effervescent tablet-assisted switchable solvent method coupled to gas chromatography-flame ionization detection as an eco-efficient, convenient-to-use, cost-effective, sensitive, rapid, and efficient method for extracting, preconcentrating, and quantifying trace amounts of diazinon in river water samples. As a switchable solvent, triethylamine (TEA) was used. In situ generation of CO2 using effervescent tablet containing Na2 CO3 and citric acid changed the hydrophobic TEA to the hydrophilic protonated triethylamine carbonate (P-TEA-C). CO2 removal from the specimen solution using NaOH caused P-TEA-C to be converted into TEA and led to phase separation, during which diazinon was extracted into the TEA phase. The salting-out process was helpful in enhancing extraction efficiency. In addition, a number of significant parameters that affect extraction recovery were examined. Under optimum conditions, the limit of detection and limit of quantitation were 0.06 and 0.2 ng/ml, respectively. The extraction recovery percentage and pre-concentration factor were obtained at 95 and 190%, respectively, and the precision (inter- and intra-day, relative standard deviation %, n = 5) was <5%.

Air-assisted in situ deep eutectic solvent decomposition followed by the solidification of floating organic droplets-liquid-liquid microextraction method for extraction of azole antifungal drugs in biological samples prior to high-performance liquid chromatography.

A free dispersive method, air-assisted in situ deep eutectic solvent decomposition followed by the solidification of floating organic droplets liquid-liquid microextraction was indicated in this study. This technique was utilized to simultaneously ascertain some azole antifungal drugs prior to high-performance liquid chromatography. In this research, a quasi-hydrophobic deep eutectic solvent was formed from tetrabutylammonium bromide and 1-dodecanol as an organic solvent at a 1:2 molar ratio. The synthesized deep decomposition in the sample solution caused in situ dispersion of extraction solvent and analytes. Air-assisted enhanced a dispersion condition in the sample solution. 1-Dodecanol as a green option was replaced with typical extraction solvents providing the advantages of a suitable freezing point near room temperature and low density. The effect of important analytical parameters on the extraction recovery of analytes was assessed. Under these optimal conditions, the limits of detection and the limits of quantitation determined were in the range of 0.5-2.8 and 1.5-9 µg/L, for water, urine and plasma samples, respectively. The intra-day and inter-day relative standard deviations (n = 5) were calculated to be 2.9-4.6 and 4.2-8.9%, respectively. The results represented the effectiveness of the developed method for the extraction and determination of analytes in biological samples.

Development of effervescence-assisted switchable polarity solvent homogeneous liquid-phase microextraction for the determination of permethrin and deltamethrin in water samples prior to gas chromatography-flame ionization detection.

An effervescent tablet-assisted switchable polarity solvent-based homogeneous liquid-phase microextraction combined with gas chromatography with flame ionization detection has been conducted for the separation, preconcentration, and detection of permethrin and deltamethrin in the river water specimens. Triethylamine (TEA) was utilized as the switchable polarity solvent in this method. The switching process was carried out by the dissolution of an effervescent tablet including an effervescency agent (sodium carbonate) and a proton donor agent (citric acid). Changing the pH of the specimen solution enhanced the conversion of TEA into protonated triethylamine carbonate through the tablet that generated carbon dioxide bubbles in situ. Finally, the addition of sodium hydroxide changed the ionization state of TEA and separated the two phases. Influential factors in the extraction were investigated. According to optimal situations, the limit of detection and the limit of quantification were 0.16 and 0.5 µg L-1 for permethrin and 0.03 and 0.1 µg L-1 for deltamethrin, respectively. The preconcentration factor was 194 in river water samples and inter- and intra-day precision (relative standard deviation %; n = 5) was <5%. The extraction recovery was obtained in the range of 93.0%-97% for permethrin and deltamethrin in water samples.

Deep eutectic solvent as the acceptor phase in three-phase hollow fiber liquid-phase microextraction for the determination of pyrethroid insecticides from environmental water samples prior to HPLC.

In this study, a deep eutectic solvent as the acceptor phase was applied in three-phase hollow fiber liquid-phase microextraction for the microextraction of two pyrethroids (permethrin as well as deltamethrin) from environmental water samples prior to HPLC-UV. A deep eutectic solvent was synthesized of tetrabutylammonium bromide-decanoic acid (in a ratio of 1:2) as an acceptor phase and 1-decanol was applied as a supported liquid membrane. Some main variables affecting the extraction recoveries, comprising the types/contents of extraction solvent and acceptor phase, stirring speed, sample phase pH and extraction time, were checked and optimized. Under optimal conditions, the detection limits and limits of quantitation determined were 0.09-0.12 and 0.29-0.39 µgl-1 for deltamethrin and permethrin, respectively. The enrichment factors were 627 and 613, while the relative standard deviations (n = 5) were 4.8 and 5.7%, for deltamethrin and permethrin, respectively. The created technique was assessed as satisfactory to ascertain the two pyrethroid poisons (permethrin and deltamethrin) in environmental water samples.

Method development for determination of imatinib and its major metabolite, N-desmethyl imatinib, in biological and environmental samples by SA-SHS-LPME and HPLC.

A salting-out-assisted switchable hydrophilicity solvent-based liquid phase microextraction (SA-SHS-LPME) was developed for the separation and determination of trace amounts of imatinib and N-desmethyl imatinib in biological and environmental samples by HPLC-UV. Triethylamine as a hydrophobic compound and protonated triethylamine carbonate as a hydrophilic one were switched by the addition or elimination of CO2 . The use of NaOH resulted in the elimination of CO2 from the sample solution, which led to the conversion of P-TEA-C into triethylamine (TEA) and as a result, the analytes was extracted and entered the TEA phase. The salting out was performed to speed up the formation of the TEA in the shape of fine droplets in the specimen solution. Furthermore, the impact of several momentous factors that influence the recovery of the extraction was investigated. Under the optimum conditions, the limit of detection and limit of quantification were obtained in ranges of 0.03-0.05 and 0.1-0.15 µg L-1 for imatinib and 0.04-0.06 and 0.13-0.20 µg L-1 for N-desmethyl imatinib, respectively. The preconcentration factor was 250. Inter- and intraday precision (RSD, n = 5) was <5%. In the case of imatinib and N-desmethyl imatinib in biological and environmental specimens, a range of 97.0-102% was obtained as the recovery.

177Lu-labeled cyclic RGD peptide as an imaging and targeted radionuclide therapeutic agent in non-small cell lung cancer: Biological evaluation and preclinical study.

Non-small cell lung carcinoma (NSCLC) is among the most lethal lung cancers responsible for 80-85% of death. αvß3 integrin receptor subtype has been identified as a lung cancer biomarker since its expression correlates with tumor progression and metastasis. The extracellular domain of the receptor forms a binding site for RGD-based sequences. Therefore, specific targeting of αvß3 integrin receptors by these short peptides can be an excellent candidate for cancer imaging and therapy. In this research, the radiolabeling of DOTA-E(cRGDfK)2 with 177Lu was efficiently implemented. The Log P value, in vivo, in vitro, metabolic stability, cellular uptake and specific binding of the radiopeptide was determined. The tumor targeting capacity and the therapeutic potential of the radiotracer was studied in A549 tumor-bearing mice. Imaging studies at different time intervals were performed by SPECT/CT. Radiochemical purity of more than 99% and Log P of -3.878 was obtained for 177Lu-labelled peptide. Radiotracer showed favorable in vivo, in vitro and metabolic stability. The radiopeptide dissociation constant (Kd) was 15.07 nM. Radiopeptide specific binding was more than 95%. Biodistribution studies showed high accumulation of the radiopeptide in tumor and rapid excretion by urinary route. Maximum tumor uptake was at 4 h post-injection. Following administration of this radiopeptide to mice, not only tumor growth was suppressed, but significant tumor shrinkage was also observed. In conclusion, this radiopeptide can be employed for staging, follow-up imaging and as peptide receptor radionuclide therapeutic agent allowing efficient therapy for NSCLC and other cancers overexpressing αvß3 integrin receptors.

Effervescent tablet-assisted demulsified dispersive liquid-liquid microextraction based on solidification of floating organic droplet for determination of methadone in water and biological samples prior to GC-flame ionization and GC-MS.

A novel effervescent tablet-assisted demulsified dispersive liquid-liquid microextraction based on the solidification of floating organic droplet was developed to determine methadone prior to gas chromatography with flame ionization detection and gas chromatography with mass spectrometry. In this method, a tablet composed of citric acid, sodium carbonate, and 1-undecanol was utilized. The resulting effervescent tablet generated carbon dioxide in situ to disperse 1-undecanol in the sample. Thus, the dispersive and extraction processes were performed in one synchronous step. An aliquot of acetonitrile as the demulsifier solvent was used for the separation of two phases instead of centrifugation. Under optimal conditions, the developed method was linear up to 50 000 µg/L with correlation coefficients higher than 0.99. Moreover, limits of detection and limits of the quantification were in the range of 3-10  and 7-30 µg/L in water and biological samples, respectively. Intra- and interday precisions (n = 6) of the spiked methadone at a concentration level of 50 µg/L were over ranges of 5.1-6.8% and 5.7-7.1%, respectively. The preconcentration factors and recovery values were obtained in the range of 140-145 and 98.1 to 101.6% in real samples, respectively.

Deep Eutectic Solvent Based Air Assisted Ligandless Emulsification Liquid-Liquid Microextraction for Preconcentration of Some Heavy Metals in Biological and Environmental Samples.

In this study, a deep eutectic solvent (DES) based on air-assisted ligandless emulsification liquid-liquid microextraction method (DES-AA-LL-ELLME) was considered for preconcentration and extraction of some metals (Cd, Ni, Pb and Cu). A 1:1 mixture of the synthesized DES and triethylamine was added as an extractant to extract metal ions in the absence of chelating agent. Tetrahydrofuran as the aprotic solvent provided a turbid state. To disperse the aggregated DES droplets into the aqueous phase, air-assisted was performed. The influence of several effective parameters was monitored. Under optimum conditions, limits of detection were found in the range of 0.31-0.99 µg L-1 with preconcentration factor from 67 to 69. The relative standard deviation (n = 10) was in the range of 2.1%-3.1% for all analytes. This procedure was applied to determine some metals in both biological and environmental samples with appropriate recoveries about 98.7%-106%.

Ultrasound-air-assisted demulsified liquid-liquid microextraction by solidification of a floating organic droplet for determination of three antifungal drugs in water and biological samples.

A novel ultrasound-air-assisted demulsified liquid-liquid microextraction by solidification of a floating organic droplet (UAAD-LLM-SFO) followed by HPLC-UV detection was developed for the analysis of three antifungal drugs in water and biological samples. In this method, 1-dodecanol was used as the extraction solvent. The emulsion was rapidly formed by pulling in and pushing out the mixture of sample solution and extraction solvent for 5 times repeatedly using a 10-mL glass syringe while sonication was performed. Therefore, an organic dispersive solvent required in common microextraction methods was not used in the proposed method. After dispersing, an aliquot of acetonitrile was introduced as a demulsifier solvent into the sample solution to separate two phases. Therefore, some additional steps, such as the centrifugation, ultrasonication, or agitation of the sample solution, are not needed. Parameters influencing the extraction recovery were investigated. The proposed method showed a good linearity for the three antifungal drugs studied with the correlation coefficients (R 2 > 0.9995). The limits of detection (LODs) and the limits of the quantification (LOQs) were between 0.01-0.03 µg L-1 and 0.03-0.08 µg L-1, respectively. The preconcentration factors (PFs) were in the range of 107-116, respectively. The precisions, as the relative standard deviations (RSDs) (n = 5), for inter-day and intra-day analysis were in the range of 2.1-4.5% and 6.5-8.5%, respectively. This method was successfully applied to determine the three antifungal drugs in tap water and biological samples. The recoveries of antifungal drugs in these samples were 92.4-98.5%. Graphical abstract Ultrasound-air-assisted demulsified liquid-liquid microextraction by solidification of a floating organic droplet for the analysis of three antifungal drugs prior HPLC-UV.

Dispersion of magnetic graphene oxide nanoparticles coated with a deep eutectic solvent using ultrasound assistance for preconcentration of methadone in biological and water samples followed by GC-FID and GC-MS.

Magnetic graphene nanoparticles coated with a new deep eutectic solvent (Fe3O4@GO-DES) were developed for efficient preconcentration of methadone. The extracted methadone was then analyzed by gas chromatography-flame ionization detection (GC-FID) or gas chromatography-mass spectrometry (GC-MS). Fe3O4@GO-DES were characterized by Fourier transform IR and X-ray diffraction techniques. Ultrasound was used to enhance the dispersion of the sorbent, with a high extraction recovery. Some parameters affecting the extraction recovery, such as pH, type of deep eutectic solvent, sample volume, amount of sorbent, extraction time, and type of eluent, were investigated. Under optimum conditions, the method developed was linear in the concentration range from 3 to 45,000 µg L-1 for GC-FID and from 0.1 to 500 µg L-1 for GC-MS, with a detection limit of 0.8 µg L-1 for GC-FID and 0.03 µg L-1 for GC-MS. The relative standard deviations (n = 6) as the intraday and interday precisions of the methadone spike at a concentration of 100 µg L-1 were 5.8% and 8.4% respectively for GC-FID. The preconcentration factor was 250. Relative recoveries from spiked plasma, urine, and water samples ranged from 95.1% to 101.5%.

Ion-pair switchable-hydrophilicity solvent-based homogeneous liquid-liquid microextraction for the determination of paraquat in environmental and biological samples before high-performance liquid chromatography.

An approach involving ion-pair switchable-hydrophilicity solvent-based homogeneous liquid-liquid microextraction coupled to high-performance liquid chromatography has been applied for the preconcentration and separation of paraquat in a real sample. A mixture of triethylamine and water was used as the switchable-hydrophilicity solvent. The pH was regulated using carbon dioxide; hence the ratio of the ionized and non-ionized form of triethylamine could control the optimum conditions. Sodium dodecyl sulfate was utilized as an ion-pairing agent. The ion-associate complex formed between the cationic paraquat and sodium dodecyl sulfate was extracted into triethylamine. The separation of the two phases was carried out by the addition of sodium hydroxide, which changed the ionization state of triethylamine. The effects of some important parameters on the extraction recovery were investigated. Under the optimum conditions (500 µL of the extraction solvent, 1 mg sodium dodecyl sulfate, 2.0 mL of 10 mol/L sodium hydroxide, and pH 4), the limit of detection and the limit of quantification were 0.2 and 0.5 µg/L, respectively, with preconcentration factor of 74. The precision (RSD, n = 10) was  <5%. The recovery of the analyte in environmental and biological samples was in the range of 90.0-92.3%.

Evaluation of ultrasound-assisted in situ sorbent formation solid-phase extraction method for determination of arsenic in water, food and biological samples.

A simple and rapid ultrasound-assisted in situ sorbent formation solid-phase extraction (UAISFSPE) coupled with electrothermal atomic absorption spectrometry detection (ET-AAS) was developed for preconcentration and determination of arsenic (As) in various samples. A small amount of cationic surfactant is dissolved in the aqueous sample containing As ions, which were complexed by ammonium pyrrolidinedithiocarbamate After shaking, a little volume of hexafluorophosphate (NaPF6) as an ion-pairing agent was added into the solution by a microsyringe. Due to the interaction between surfactant and ion-pairing agent, solid particles are formed. The alkyl groups of the surfactant in the solid particles strongly interact with the hydrophobic groups of analytes and become bound. Sonication aids the dispersion of the sorbent into the sample solution and mass transfer of the analyte into the sorbent, thus reducing the extraction time. The solid particles are centrifuged, and the sedimented particles can be dissolved in an appropriate solvent to recover the absorbed analyte. After separation, total arsenic (As(III) and As(V)) was determined by ET-AAS. Several experimental parameters were investigated and optimized. A detection limit of 7 ng L(-1) with preconcentration factor of 100 and relative standard deviation for 10 replicate determinations of 0.1 µg L(-1) As(III) were 4.5% achieved. Consequently, the method was applied to the determination of arsenic in certified reference materials, water, food and biological samples with satisfactory results.

Synthesis, Radiolabeling, and Biodistribution Study of a Novel DOTA-Peptide for Targeting Vascular Endothelial Growth Factor Receptors in the Molecular Imaging of Breast Cancer.

As angiogenesis plays a pivotal role in tumor progression and metastasis, leading to more cancer-related deaths, the angiogenic process can be considered as a target for diagnostic and therapeutic applications. The vascular endothelial growth factor receptor-1 (VEGR-1) and VEGFR-2 have high expression on breast cancer cells and contribute to angiogenesis and tumor development. Thus, early diagnosis through VEGFR-1/2 detection is an excellent strategy that can significantly increase a patient's chance of survival. In this study, the VEGFR1/2-targeting peptide VGB3 was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), using 6-aminohexanoic acid (Ahx) as a spacer to prevent steric hindrance in binding. DOTA-Ahx-VGB3 was radiolabeled with Gallium-68 (68Ga) efficiently. An in vitro cell binding assay was assessed in the 4T1 cell line. The tumor-targeting potential of [68Ga]Ga-DOTA-Ahx-VGB3 was conducted for 4T1 tumor-bearing mice. Consequently, high radiochemical purity [68Ga]Ga-DOTA-Ahx-VGB3 (RCP = 98%) was prepared and stabilized in different buffer systems. Approximately 17% of the radiopeptide was internalized after 2 h incubation and receptor binding as characterized by the IC50 value being about 867 nM. The biodistribution and PET/CT studies revealed that [68Ga]Ga-DOTA-Ahx-VGB3 reached the tumor site and was excreted rapidly by the renal system. These features convey [68Ga]Ga-DOTA-Ahx-VGB3 as a suitable agent for the noninvasive visualization of VEGFR-1/2 expression.

Novel Gd-DTPA-peptide for targeted breast tumor magnetic resonance imaging.

The prevalence of breast cancer underscores the imperative for early diagnosis in guiding treatment decisions. This study introduces a novel contrast agent, Gd-DTPA-VGB3, derived from the peptide VGB3 targeting vascular endothelial growth factor receptor-1 (VEGFR1) and VEGFR2, to enhance the contrast of conventional drug Magnevist in breast tumor MRI. The MRI contrast agent was synthesized on rink amide resin via Fmoc strategy, incorporating amino acids, and coupling to diethylenetriaminepentaacetic acid (DTPA). Gadolinium (Gd)-DTPA-VGB3 displayed specific binding to VEGFR1/2 in a displacement binding assay. Gd-DTPA-VGB3 exhibited minimal cytotoxicity to normal MCF-10 cells while inhibiting 4T1 mammary carcinoma cell proliferation. Compared to Magnevist, Gd-DTPA-VGB3 demonstrated a 2.8-fold increase in contrast-to-noise ratio (CNR) (355 vs. 125). Gd-DTPA-VGB3 exhibited enhanced accumulation in 4T1 tumor-bearing mice, resulting in significant signal intensity improvement. The findings highlight Gd-DTPA-VGB3's specific binding to VEGFRs, substantiating its potential as a candidate for enhancing MRI contrast in breast cancer diagnostics.

Synthesis, in vitro aerobic and hypoxic cytotoxicity and radiosensitizing activity of novel metronidazole tethered 5-fluorouracil.

BACKGROUND AND THE PURPOSE OF THE STUDY: Several 2, 4-dinitrophenyl and 2,4-dinitrophenylamine tethered 5-FU (5-fluorouracil) compared to their components have shown minimal or no cytotoxicity to HT-29 cell line under aerobic conditions but high cytotoxicity and radiosensitizing effects under hypoxic conditions. In the present study the cytotoxicity and radiation potentiation of three novel analogues of these compounds by replacing 2,4-dinitrophenyl moiety with 2-methyl-5-nitroimidazole, a known radiosensitizer and cytotoxic agent was investigated. METHODS: Tethered compounds 7-9 were prepared by the reaction of 1-(t-butoxycarbonyl)-5-fluorouracil 6 with metronidazole esters 2-4 followed by removal of the t-butoxycarbonyl protecting group. Cytotoxicity of compounds in HT-29 cells with or without radiation were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), propidium iodide (PI)-digitonin and clonogenic assays. RESULTS: Tethered compounds 7-9 induced time-and concentration-dependent cytotoxicity under hypoxia but had no significant effect under aerobic conditions. These compounds also showed selective and concentration- dependent radiosensitization effects under hypoxic conditions. CONCLUSION: Tethered compounds 7-9 compared to 5-FU 5 showed minimal cytotoxicities under aerobic and selective radiosensitizing activities under hypoxic conditions. Also effects of these compounds were higher than those of metronidazole 1 which is a known cytotoxin and radiosensitizer under hypoxic conditions.

Effervescent tablet-assisted deep eutectic solvent based on magnetic nanofluid for liquid phase microextraction of tyrosine kinase inhibitors in plasma samples by high-performance liquid chromatography.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are efficient anti-cancer drugs. The analysis of TKIs in the treatment of cancer is important to achieve the highest anti-cancer effects with minimal toxicities. Herein, we report an efficient effervescent tablet-assisted deep eutectic solvent based on nanofluid (ETA-DES-NF) combined with HPLC-UV for the determination of three anti-cancer drugs (erlotinib, imatinib, and nilotinib) in human plasma samples. METHODS: In this method, a magnetic nanofluid composed of deep eutectic solvent (DES) and Fe3O4@SiO2 nanoparticles was used as an extraction solvent. The deep eutectic solvent acted as a carrier and stabilizer for Fe3O4@SiO2 nanoparticles. A tablet was used in the nanofluid for dispersion. The effervescent tablet was implemented to generate in situ CO2 and provide the effective dispersion of the sorbent into the sample solution for diminishing the extraction time and improving the extraction efficiency. Moreover, the magnetic nanofluid enhanced phase separation efficiency without centrifugation to collect the organic solvent. RESULTS: The synthesized nanofluid was characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and vibrating sample magnetometry (VSM). The impact of main parameters, including the type and volume of DES, the composition of the tablet, the composition of the nanofluid and the composition of eluent, were optimized. According to the optimized conditions, the limits of detection (LODs) and the limits of quantitation (LOQs) were from 0.5-0.8 to 1.5-2.4 µg L-1 for imatinib, erlotinib, and nilotinib, respectively. The intra-day and inter-day relative standard deviations (RSD% n = 5) were determined to be 3.1-5% and 6.4-7.5%, respectively. CONCLUSIONS: The developed method displayed high sensitivity, low consumption of solvent, low cost, simplicity, high recoveries, short extraction time, and good repeatability for determination of three anti-cancer drugs in human plasma samples.

Cytotoxicity and radiosensitising activity of synthesized dinitrophenyl derivatives of 5-fluorouracil.

BACKGROUND AND THE PURPOSE OF THE STUDY: Dual functional agents in which nitroaromatic or nitroheterocyclic compounds are attached through a linker unit to mustards and aziridines have shown higher cytotoxicities than the corresponding counterparts to both aerobic and hypoxic cells and enhanced radiosensitizing activity. In the present investigation cytotoxicity and radiosensitizing activity of 2,4-dinitrobenzyl, 2,4-dinitrobenzoyl, and 2,4-dinitrophenacetyl derivatives of 5-fluorouracil which was assumed to release cytotoxic active quinone methidide and 5-fluorouracil under hypoxic conditions on HT-29 cell line under both aerobic and hypoxic conditions was investigated. METHODS: 5-fluorouracil derivative X-XIII were prepared by the reaction of the corresponding di-nitro substituted benzyl, benzoyl and phenacetyl halides with 5-fluorouracil protected at N-1 with di-t-butoxydicarbonate (BOC) in dimethyl formamide (DMF) in the presence of the potassium carbonate followed by hydrolysis of the blocking group by potassium carbonate in methanol. Cytotoxicity of fluorouracil VIII and tested compounds X-XIII against HT-29 cell line under both aerobic and hypoxic conditions after 48 hrs incubation were measured by determination of the percent of the survival cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and percent of the dead cells using propidium iodide(PI)-digitonine assay and results were used to calculate the corresponding IC(50) values. Radiosensitization experiments were carried out by irradiation of the incubations with a (60)Co source and clonogenic assay was performed to determine the cell viabilities following treatment with the tested compounds and/or radiation. Sensitization Enhancement Ratio (SER) of each tested compound was obtained from the radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively. RESULTS AND MAJOR CONCLUSION: Findings of the present study showed that alkylation or acylation of 5-fluorouracil result in compounds which have little or no cytotoxicity and radiosensitizing activity under aerobic conditions, but have high cytotoxicity and radiosensitizing effects under hypoxic conditions. Furthermore radiosensitizing activities of compounds under hypoxic conditions increased by increase in their concentrations and SER of the tested 5-FU derivatives at concentrations higher than 50 µmol were equal or higher than 1.6 which is the minimum effective SER of a radiosensitizer in an in vitro assay.

Fabrication of an SPME fiber based on ZnO@GA nanorods coated onto fused silica as a highly efficient absorbent for the analysis of cancer VOCs in water and urine.

Analysis of volatile organic compounds (VOCs) secreted in urine, blood, breath, etc. is a new method for monitoring the metabolism and biochemistry of the human body. However, due to the complexity of samples, a pre-concentration step is necessary before the final analysis with gas chromatography-mass spectroscopy (GC-MS). Therefore, miniaturized extraction methods such as solid-phase microextraction (SPME) can be a promising and simple pre-concentration technique. Different strategies have been adopted for the fabrication or modification of SPME fibers. This study presents the preparation and characterization of glass optical fibers coated with ZnO nanorods functionalized with gallic acid (ZnO@GA nanorod) as SPME adsorbent in GC-MS. ZnO@GA nanorods were synthesized separately and then coated onto the fibers. The coated fibers were characterized by using field emission scanning electron microscopy coupled with energy dispersive analysis of X-rays (FESEM/EDAX) and Fourier transform infrared spectroscopy (FTIR) techniques. Possessing a high surface to volume ratio of ZnO nanorods and functional groups of GA, the ZnO@GA nanorod-based SPME fibers exhibited good extraction performance for VOCs comparing with the commercial polydimethylsiloxane (PDMS) coated fibers. Under optimal conditions (NaCl concentration, 30% w/v; extraction time of 25 min; pH, 5-7 and stirring rate of 400 rpm) ZnO@GA nanorods coated fibers achieved low detection limits (0.32-4.8 µg/L), low quantification limits (1.8-16.3 µg/L) and good linearity (5-1000 µg/L) for selected VOCs. The repeatability (n = 3) for a single fiber was within the range of 4.1-7.9% (intra-day) and 5.7-9.6% (inter-day) while the reproducibility (n = 3) of fiber-to-fiber were in the range of 4.7% and 9.9%. This method was successfully used for the determination of six VOCs in water and urine with satisfactory recoveries of 90-112%. ZnO@GA nanorod coated fibers, despite possessing a much thinner coating compared to the commercial fibers, revealed a better overall extraction efficiency towards VOCs. These results indicated that the ZnO@GA provided a promising alternative in sample pretreatment and analysis in GC-MS.