Fluorescence based methodology with greenness consideration for concurrent estimation of anti-allergic medication; application to dosage form.

A green, sensitive and rapid spectrofluorimetric method for quantitative assay of an anti-allergic medication composed of montelukast and fexofenadine mixture in raw materials and dosage form was developed. The method was based on measuring the synchronous fluorimetric peak without interference, pre-separation or pre-extraction procedures. Montelukast was analyzed at 360 nm while fexofenadine was measured at 263 nm using Δλ = 20 nm for both drugs using ethanol as diluting solvent and acetate buffer of pH 4. The assay was rectilinear over the concentration range of 1.0-10.0 µg/mL for fexofenadine and 0.1-0.6 µg/mL for montelukast. The method was full validated according to ICH guidelines. The applicability of the method enables the assay of both drugs in raw materials, synthetic mixture as well as combined tablets. Moreover, the greenness of the method was assessed using different methods including; analytical eco-scale, GAPI and AGREE. All of these methods confirm that the proposed method is an eco-friendly method.

A carboethoxy quinoline-Derived Schiff base chemosensor: Crystal structure, selective Hg2+ ion detection and its computational study.

Environmental monitoring of mercury (Hg2+) ions has become increasingly important as a result of their detrimental effects on biological organisms at all levels. To recognize toxic metal ions, utmost effort has been devoted to developing new materials that are highly selective, ultra-sensitive, and provide rapid response. In this context, a new chemosensor, 2-imino [N - (N-amido phenyl)]-6-methoxy-3-carbethoxy quinoline (L), has been synthesized by combining 2-formyl-6-methoxy-3-carbethoxy quinoline and benzhydrazide and it has been extensively characterized by NMR, FTIR, ESI-Mass and SCXRD analysis. Probe L has excellent specificity and sensitivity toward Hg2+ ions in semi-aqueous solutions, with a detection limit of 0.185 µM, regardless of the presence of other interfering cations. Chromogenic behavior was demonstrated by the L when it changed the color of the solution from colorless to light yellow, a change that can be observed visually. The probe L forms a 1:1 stochiometric complex with an estimated association constant (Ka) of 6.74 × 104 M-1. The 1H NMR change and density functional theory calculations were analyzed to improve our understanding of the sensing mechanism. Also, an inexpensive and simple paper-based test kit has been developed for the on-site detection of mercury ions in water samples.

A novel pH-sensitive hemi-cyanine containing tetrahydropyridine ring near-infrared fluorescence probe with lysosome-targeting ability.

In recent years, hemi-cyanine dyes have been widely used as biological probes due to their red-light emission characteristics and high fluorescence quantum yield. In this study, we synthesized a novel hemi-cyanine dye containing a tetrahydropyridine ring. A lysosomal target was introduced into its structure to create a new pH-sensitive near-infrared fluorescent probe that successfully targeted lysosomes. The results showed that when the probe solution was excited at the absorption wavelength of 650 nm, its fluorescence emission wavelength was about 700 nm, and the peak intensity changed with different pH values in a wide range. Therefore, this probe enabled non-invasive detection of changes in the acidic environment of lysosomes in living organisms and showed good imaging capabilities. Moreover, the probe displays high sensitivity and good stability. The theoretical calculation of a probe structure has also been completed to discuss the relationship between structure and property.

Quinoline-quinoline schiff-base as an effective chromogenic, fluorogenic, and smartphone assisted RGB detection of Pb2+ ion in near aqueous medium.

A novel multimode colorimetric and fluorescent chemosensor was developed using an 8-hydroxy quinoline carbaldehyde Schiff base with a quinoline hydrazide probe (E)-2-((2-(quinolin-2-yl)hydrazineylidene)methyl)quinolin-8-ol (L). NMR (1H & 13C), FTIR, and HR-mass spectral characterization techniques confirmed the probe L structural conformation. As Probe L contacts Pb2+ ions, a color change and turn-off emission can be visually detected in EtOH:H2O (1:1, v/v, pH = 7.21) medium. The probe displays a good emission at 440 nm due to the combined ESIPT and ICT process. The Pb2+ ion interacts with the probe and selectively quenches fluorescence by inhibiting ESIPT and >CN- isomerization. As per Job's plot, L-Pb2+ complex formation occurred in a 1:1 stoichiometric ratio, with association constant (Ka) and quenching constant (Ksv) estimated at 1.52 × 105 M-1 and 4.12 × 105 M, respectively. The detection limits of Pb2+ by spectrophotometric and spectrofluorometric were 1.99 µM (41 ppb) and 23.4 nM (485 ppt), respectively. Additionally, the test paper kit and RGB tool were used to monitor the color changes of L with Pb2+ and the LOD was found to be 5.99 µM (125 ppb). Its recognition mechanism has been verified by 1H NMR, ESI-mass, and theoretical studies.

Solvent-free automated thermal desorption-gas chromatography/mass spectrometry for direct screening of hazardous compounds in consumer textiles.

The global production of textiles utilizes numerous large-volume chemicals that may remain to some extent in the finished garments. Arylamines, quinolines, and halogenated nitrobenzene compounds are possible mutagens, carcinogens and/or skin sensitizers. For prevention, control of clothing and other textiles must be improved, especially those imported from countries without regulations of textile chemicals. An automated analytical methodology with on-line extraction, separation, and detection would largely simplify screening surveys of hazardous chemicals in textiles. Automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) was developed and evaluated as a solvent-free, direct chemical analysis for screening of textiles. It requires a minimum of sample handling with a total run time of 38 min including sample desorption, chromatographic separation, and mass spectrometric detection. For most of the studied compounds, method quantification limit (MQL) was below 5 µg/g for 5 mg of textile sample, which is sufficiently low for screening and control of quinoline and arylamines regulated by EU. Several chemicals were detected and quantified when the ATD-GC/MS method was applied in a limited pilot screening of synthetic fiber garments. A number of arylamines were detected, where some of the halogenated dinitroanilines were found in concentrations up to 300 µg/g. This is ten times higher than the concentration limit for similar arylamines listed by the EU REACH regulation. Other chemicals detected in the investigated textiles were several quinolines, benzothiazole, naphthalene, and 3,5-dinitrobromobenzene. Based on the present results, we suggest ATD-GC/MS as a screening method for the control of harmful chemicals in clothing garments and other textiles.

Simultaneous Determination of Montelukast Sodium and Loratadine by Eco-Friendly Densitometry and Spectrophotometric Methods.

Recently, the aim of analytical community is to reduce the usage of hazardous chemicals; so eco-friendly, rapid, selective and cost-effective methods were developed for simultaneous determination of montelukast sodium (MKT) and loratadine (LRT). The first method was based on chromatographic separation performed on precoated silica gel 60 GF254 plates with ethyl acetate-ethanol 9: 1 (v/v) as the mobile phase. The developed plates were scanned and quantified at 260 nm. The method gives linear correlation over concentration ranges of 0.3-3.6 µg/spot and 0.2-4.0 µg/spot for MKT and LRT, respectively. It was also successfully applied to analysis of both drugs in their pharmaceutical preparation and human plasma. The other methods are UV-spectrophotometric methods based on smart spectra manipulating to zero order spectrum of each drug. These methods are named response correlation (RC), a-centering and ratio derivative methods. RC and a-centering methods were dependent on the presence of an isosbestic point between the overlapped spectra of both drugs. While ratio derivative method based on manipulation of the ratio spectra of both drugs. The two drugs obey Beer-Lambert law over the concentration ranges of 3.0-30.0 µg/mL in the three spectrophotometric methods. Moreover, the greenness of the developed methods is assessed using suitable analytical Eco-Scale and Green Analytical Procedure Index.

A benzothiophene-quinoline-based targetable fluorescent chemosensor for detection of viscosity and mitochondrial imaging in live cells.

Mitochondria are the sites of respiration in cells, and they participate in many indispensable biological processes. Because variations in mitochondrial viscosity can lead to dysfunctions of mitochondrial structure and function (and even induce malignant diseases), new sensors that can accurately monitor changes in mitochondrial viscosity are essential. To better investigate these changes, we report the development and evaluation of a novel benzothiophene-quinoline-based fluorescent chemosensor (BQL) that was designed especially for monitoring mitochondrial viscosity. BQL demonstrated a large Stokes shift (minimizing interference from autofluorescence) and a good response to viscosity (using the TICT principle). Moreover, BQL demonstrated little to no pH-dependency, polarity-dependency, or interference from other analytes. Thus, BQL has an excellent specificity for viscosity. BQL was used to monitor viscosity changes in mitochondria induced by ion carriers, and was used to report on viscosity in real time during mitophagy. To sum up, BQL provided a new approach for detecting viscosity in living cells and in vivo. BQL should prove to be an excellent tool for the analysis of viscosity changes in live cells.

Heterogeneous electro-Fenton using three-dimension Fe-Co-Bi/kaolin particle electrodes for degradation of quinoline in wastewater.

Wastewater containing quinoline has become a common pollutant in water and soil environments, which poses a threat to human health due to its carcinogenicity, teratogenicity, and mutagenicity. Quinoline's stability and toxicity hinders its degradation by conventional physicochemical and biological methods. In this contribution, Fe-Co-Bi/kaolin particle electrodes were prepared for the efficient degradation of quinoline in wastewater, and characterized by using scanning electron microscope, X-ray diffraction, pyridine-IR, Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy, and four-probe resistivity test. Parameters affecting the degradation efficiency were optimized to be the particle electrode dosage of 40 g/L, pH 3.5, H2O2 addition of 67.6 mmol/L, electrical conductivity of 12.7 ms/cm, and voltage of 20 V. The constructed three-dimensional catalytic particle electrode system (3D-CPE) achieved 92.1% removal rate of chemical oxygen demand (COD) under the optimal conditions. Hydroxyl radicals (•OH) generated in the 3D-CPE process were identified by radical scavenging tests and electron spin response analysis. To unravel the degradation mechanism, the intermediate products were identified by using high performance liquid chromatography-mass spectrometry. The degradation mechanism was discussed with the help of theoretical calculation.

Suspect and non-target screening of chemicals in clothing textiles by reversed-phase liquid chromatography/hybrid quadrupole-Orbitrap mass spectrometry.

The global manufacturing of clothing is usually composed of multistep processes, which include a large number of chemicals. However, there is generally no information regarding the chemical content remaining in the finished clothes. Clothes in close and prolonged skin contact may thus be a significant source of daily human exposure to hazardous compounds depending on their ability to migrate from the textiles and be absorbed by the skin. In the present study, twenty-four imported garments on the Swedish market were investigated with respect to their content of organic compounds, using a screening workflow. Reversed-phase liquid chromatography coupled to electrospray ionization/high-resolution mass spectrometry was used for both suspect and non-target screening. The most frequently detected compound was benzothiazole followed by quinoline. Nitroanilines with suspected mutagenic and possible skin sensitization properties, and quinoline, a carcinogenic compound, were among the compounds occurring at the highest concentrations. In some garments, the level of quinoline was estimated to be close to or higher than 50,000 ng/g, the limit set by the REACH regulation. Other detected compounds were acridine, benzotriazoles, benzothiazoles, phthalates, nitrophenols, and organophosphates. Several of the identified compounds have logP and molecular weight values enabling skin uptake. This pilot study indicates which chemicals and compound classes should be prioritized for future quantitative surveys and control of the chemical content in clothing as well as research on skin transfer, skin absorption, and systemic exposure. The results also show that the current control and prevention from chemicals in imported garments on the Swedish market is insufficient.

Response Surface Methodology of Quantitative of Heterocyclic Aromatic Amines in Fried Fish Using Efficient Microextraction Method Coupled with High-Performance Liquid Chromatography: Central Composite Design.

Meat and meat products are indispensable part of our diet. Heat processing of these tasty foods such as fried fish causes to form heterocyclic aromatic amines (HAAs). The sources of heating have directly affected on the level and type of HAAs. In this research, 2-amino-1-methyl-6-phenylimidazo [4'5-b] pyridine (PhIP), 2-amino-3-methylimidazo [4,5-f]quinolone (IQ), 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ) and 2-amino-3,4-dimethylimidazo [4,5-f] quinoxaline (MeIQx) were determined using an efficient analytical methodology coupled with high-performance liquid chromatography. The effective parameters were optimized by central composite design. The results of this survey demonstrated that rang of relative standard deviation were between 4.5 and 8.2, extraction recoveries were obtained 86-97% and limits of detection were between 0.40 and 0.63 for 4 HAAs. The amounts of HAAs found in 20 different fried fish samples were between 0 and 4.8 ng g-1. PhIP with 1.57 ng g-1 and MeIQ with 2.08 ng g-1 have the lowest and highest average level of HAAs, respectively.

An improved staining method of cell cycle analysis with Sybr Green I for fungi: Cryptococcus neoformans and Saccharomyces cerevisiae.

Cryptococcus neoformans is a pathogenic fungus which causes millions of deaths and infections, especially threatening immunocompromised individuals. During the development of new drugs, the ubiquitination has been found to play an important role in the regulation of the virulence and cell cycle of this fungus. Based on this mechanism, ubiquitination-related mutant strains exhibiting cell cycle arrest have been established for drug development for the fungus. However, flow cytometry detection of the cell cycle in fungi is generally difficult because the thick cell wall and capsule of fungi generally contribute to a nonspecific signal of cytometry. In this study, an improved method, derived from Saccharomyces cerevisiae assays, is developed to specifically stain C. neoformans, in whose cell cycle the G1 and G2 peaks are separated enough to be allowed for cell cycle analysis. As a result, the improved method facilitates the detection of the alterations in the cell cycle of C. neoformans with a mutation that results in cell cycle arrest, which distinctly delays the cell division of C. neoformans. Thus, the improved method reported here provides detailed technical information regarding assays on C. neoformans and, more importantly, offers a solution for assessing the cell cycle in other fungi in the future. Abbreviation: PI: propidium iodide.

A Review of Different Analytical Techniques for Fexofenadine Hydrochloride and Montelukast Sodium in Different Matrices.

Fexofenadine hydrochloride is an antihistamine agent used for the treatment of allergic disorders like rhinitis. It is a second generation antihistamine. Montelukast sodium is an anti-asthmatic agent and leukotriene receptor antagonist used in the treatment of respiratory disorders. This article exemplifies the reported analytical methods like electrometric methods, ultraviolet spectroscopy, mass spectroscopy, thin layer chromatography, high performance liquid chromatography, high performance thin layer chromatography and tandem spectroscopy for determination of fexofenadine HCl and montelukast sodium in dosage form and in biological matrices. This review covers almost all the analytical methods for fexofenadine hydrochloride and montelukast sodium form 1968-2018 years. Complete analytical validation parameters reported are discussed in this review for both analytes. Among various analytical methods, HPLC and UV-visible spectrophotometry were found to be the most extensively used methods by the researchers.

Determination of intracellular anlotinib, osimertinib, afatinib and gefitinib accumulations in human brain microvascular endothelial cells by liquid chromatography/tandem mass spectrometry.

RATIONALE: Brain metastases are a common complication in patients with non-small-cell lung cancer (NSCLC). Anlotinib hydrochloride is a novel multi-target tyrosine kinase inhibitor (TKI) exhibiting a superior overall response rate for brain metastases from NSCLC. The penetrability of anlotinib and three generations of epidermal growth factor receptor (EGFR) TKIs (osimertinib, afatinib and gefitinib) into brain microvascular endothelial cells (HBMECs) was compared. METHODS: A sensitive quantification method for the four TKIs was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). Anlotinib and the three EGFR TKIs were separated on an ACQUITY BEH C18 column after a direct protein precipitation, and then analyzed using electrospray ionization in positive ion mode. The linearity, accuracy, precision, limit of quantification, specificity and stability were assessed. RESULTS: The four analytes could be efficiently quantified in a single run of 3.8 min. The validation parameters of all analytes satisfy the acceptance criteria of bioanalytical method guidelines. The calibration range was 0.2-200 ng mL-1 for anlotinib and gefitinib, 1-500 ng mL-1 for osimertinib and 1-200 ng mL-1 for afatinib. The penetration of anlotinib across HBMECs was comparable with that of afatinib and gefitinib but less than that of osimertinib. CONCLUSIONS: A sensitive LC/MS/MS method to simultaneously measure anlotinib, osimertinib, afatinib and gefitinib in cell extracts was successfully validated and applied to determine their uptake inside HBMECs, which could pave the way for future research on the role of anlotinib in NSCLC brain metastases.

A novel magnetic solid-phase extraction method for detection of 14 heterocyclic aromatic amines by UPLC-MS/MS in meat products.

The current study developed a cheap and effective method for the simultaneous extraction of 14 heterocyclic aromatic amines (HAAs) in food matrix. Core-shell Fe3O4@PDA nanoparticles were constructed and acted as the magnetic solid-phase extraction adsorbent to separate and purify HAAs from meat products for the first time. Then, UPLC-MS/MS technique was employed to identify and quantify the HAAs easily. Fe3O4@PDA nanoparticles were synthesized and characterized successfully. Totally 14 HAAs were completely separated in 19.99 min with good regression coefficients. LODs and LOQs were in the range of 0.013-0.247 ng/g and 0.056-0.803 ng/g, respectively. The intra-day precisions and inter-day precisions were below 9%. Except for IQ[4,5-b], Phe-p-1, PhIP, other 11 types of HAAs (DMIP, 1,5,6-TMIP, IQ, IQx, MeIQ, MeIQx, 7,8-DiMeIQx, AαC, MeAαC, Harman, Norharman) could acquire relatively high recoveries (71.06%-108.49%). The proposed method was successfully devoted to the evaluation of HAAs levels in 8 commercial meat products to verify the adaptability.

Formation of a Thiol-Ene Addition Product of Asthma Medication Montelukast Caused by a Widespread Tin-Based Thermal Stabilizer.

We report the formation and characterization of two diastereomeric thiol-ene addition products of the asthma medication Montelukast within chewing tablets. Widespread tin-based thermal stabilizers dioctyltin bis(2-ethylhexyl thioglycolate) and monooctyltin tris(2-ethylhexyl thioglycolate), used in the manufacturing process of the medication's forming foil, were identified as the source of the thiol reactant, showing that these stabilizers may play a part in the degradation of Montelukast and APIs with functionalities similar to those of Montelukast, which should be considered during development of medication. The isolation and analysis of these impurities was performed by HPLC and UV-vis spectroscopy. HRMS and NMR data were collected to characterize and determine the structures of these compounds.

Non-rhizobial endophytic (NRE) yeasts assist nodulation of Rhizobium in root nodules of blackgram (Vigna mungo L.).

The signal orchestration between legumes and the rhizobia attribute to symbiotic nitrogen fixation through nodule formation. Root nodules serve as a nutrient-rich reservoir and harbor diverse microbial communities. However, the existence of non-rhizobial endophytes (NRE) and their role inside the root nodules are being explored; there is no evidence on yeast microflora inhabiting nodule niche. This study focused on unraveling the presence of yeast in the root nodules and their possible function in either nodulation or signal exchange. From the root nodules of blackgram, two yeast strains were isolated and identified as Candida glabrata VYP1 and Candida tropicalis VYW1 based on 18S rRNA gene sequencing and phylogeny. These strains possessed plant growth-promoting traits viz., IAA, ACC deaminase, siderophore, ammonia, and polyamine production. The functional capacity of endophytic yeast strains, and their interaction with Rhizobium sp. was further unveiled via profiling volatile organic compounds (VOC). Among the VOCs, α-glucopyranoside and pyrroloquinoline pitches a pivotal role in activating lectin pathways and phosphorous metabolism. Further, lectin pathways are crucial for nodulating bacterium, and our study showed that these endophytic yeasts assist nodulation by Rhizobium sp. via activating the nod factors. The plant growth-promoting traits of NRE yeast strains coupled with their metabolite production, could recruit them as potential drivers in the plant-microbe interaction.

Surface sensing triggers a broad-spectrum antimicrobial response in Pseudomonas aeruginosa.

Interspecies bacterial competition may occur via cell-associated or secreted determinants and is key to successful niche colonization. We previously evolved Pseudomonas aeruginosa in the presence of Staphylococcus aureus and identified mutations in the Wsp surface-sensing signalling system. Surprisingly, a ΔwspF mutant, characterized by increased c-di-GMP levels and biofilm formation capacity, showed potent killing activity towards S. aureus in its culture supernatant. Here, we used an unbiased metabolomic analysis of culture supernatants to identify rhamnolipids, alkyl quinoline N-oxides and two siderophores as members of four chemical clusters, which were more abundant in the ΔwspF mutant supernatants. Killing activities were quorum-sensing controlled but independent of c-di-GMP levels. Based on the metabolomic analysis, we formulated a synthetic cocktail of four compounds, showing broad-spectrum anti-bacterial killing, including both Gram-positive and Gram-negative bacteria. The combination of quorum-sensing-controlled killing and Wsp-system mediated biofilm formation endows P. aeruginosa with capacities essential for niche establishment and host colonization.

Reactive carbonyls and the formation of the heterocyclic aromatic amine 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ).

Reactions involving reactive carbonyls, creatinine, and ammonia-producing compounds were investigated in order to clarify the formation of the heterocyclic aromatic amine (HAA) 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ). Obtained results showed that MeIQ was only produced when 2-butenal (crotonaldehyde) was present. Reaction yields depended on the pH, with a maximum around pH 6.5, and on concentrations of crotonaldehyde and creatinine. Ammonia was also required for MeIQ formation, but ammonia was produced by creatinine decomposition. The amount of MeIQ formed increased with reaction time, temperature, and oxygen content in the reaction atmosphere. Activation energy for MeIQ formation from crotonaldehyde, creatinine, and glutamine was 72.2 ± 0.4 kJ·mol-1. A reaction pathway that explains MeIQ formation is proposed. Obtained results suggest a main role of reactive carbonyls formed in foods (the food carbonylome) on HAA formation. In addition, they provide scientific basis for the understanding of how HAAs are formed and could be mitigated.

A novel HPLC method developed and validated for the detection and quantification of atorvastatin, fluvastatin, pitavastatin and pravastatin during transdermal delivery studies.

An HPLC method was developed and validated to quantify and identify several statins (atorvastatin, fluvastatin, pitavastatin and pravastatin) that were used during transdermal drug delivery. The method proved to be most effective with a Restek Ultra C18, 250 x 4.6 mm, 5 µm column, a flow rate of 1.0 ml/min, UV detection at 240 nm and injection volume of 10 µl. The mobile phase used was acetonitrile/Milli-Q® water with 0.1% orthophosphoric acid starting with 30% acetonitrile, which increased linearly to 70% (after 4 min) for up to 10 min and then re-equilibrated to start conditions. This HPLC method indicated linearity (correlation coefficient (R²) of 1) within the concentration range of 0.05-200.00 µg/ml and had an average recovery of 98-103%. Limit of detection (LOD) and limit of quantification (LOQ) showed that statins could still be identified at concentrations of 0.004-0.006 µg/ml with the exception of atorvastatin (quantifiable at 0.013-0.035 µg/ml). Specificity performed during method validation, confirmed that the method was suitable for accurate detection and quantification of the statins when included in the transdermal formulations with other excipients.

Sensitive fluorometric determination of quinclorac residues in rice.

Rice is one of the most important foods in the world due to its high nutritional value and production. Quinclorac, a selective herbicide, is one of the most detected pesticide residues in rice crops according to pesticide monitoring studies. Common methods for the determination of quinclorac in rice are very time-consuming and labour-intensive, so it is important to develop alternative sensitive and simple analytical methods able to detect quinclorac in food samples. Here we propose a fluorometric method for the screening of this herbicide at excitation/emission wavelengths of 238/358 nm/nm, respectively. A modified QuEChERS method was selected for sample treatment due to its simplicity and high recovery yields. The proposed method presents a detection limit of 2.5 ng mL-1 and satisfactory precision. Recovery experiments were performed in different kinds of rice (white and brown) at or below the Maximum Residue Limit established in European Union (5 mg kg-1), obtaining values close to 100%. All these characteristics ensure that the proposed method fulfils the requirements for its application in food control.