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The COVID-19 pandemic has highlighted the urgent need for effective antiviral agents. One such promising drug is nirmatrelvir (NIRMA), which has demonstrated the ability to inhibit viral replication and reduce hospitalization and mortality rates. In the field of analytical chemistry, carbon quantum dots (CQDs) derived from fruit peel waste have gained attention for their eco-friendly and cost-effective properties. In this study, CQDs were synthesized from the peel biomass waste of yellow lupin and utilized for the spectrofluorometric determination of NIRMA in pharmaceutical tablets. The proposed method offers simplicity and speed compared to existing methods. The synthesis process involved washing and grinding the peel waste, followed by heating in propylene glycol and purification using a dialysis membrane. The resulting CQD solution showed fluorescence at an emission wavelength of 411 nm upon excitation at 325 nm. The validation of the method, including linearity, range, limit of detection and quantification, accuracy, precision, and robustness, was conducted following ICH guidelines. The fluorescence intensities exhibited a linear relationship with increasing NIRMA concentration in the range of 15-150 µg/mL. The limit of detection found to be 4.0 μg/mL, with %relative standard deviations ≤ 1.46. This spectrofluorometric method represents a novel approach for the determination of NIRMA using CQDs derived from yellow lupin peel waste., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The increasing prevalence of multidrug-resistant pathogens is a critical public health issue, necessitating the development of alternative antibacterial agents. Examples of these pathogens are methicillin-resistant Staphylococcus aureus (MRSA) and the emergence of "pan-resistant" Gram-negative strains, such as Pseudomonas aeruginosa and Acinetobacter baumannii, which occurred more recently. This review examines various emerging materials with significant antibacterial activities. Among these are nanomaterials such as quantum dots, carbon quantum dots, metal-organic frameworks (MOFs), covalent organic frameworks (COFs), and layered double hydroxides, all of which demonstrate excellent antibacterial properties. Interestingly, including antibacterial agents within the structure of these materials can help avoid bacterial resistance and improve the long-term efficacy of the materials. Additionally, the antibacterial potential of liquid solvents, including ionic liquids and both deep eutectic solvents and natural deep eutectic solvents, is explored. The review discusses the synthesis methods, advantages, and antibacterial efficacy of these new materials. By providing a comprehensive overview of these innovative materials, this review aims to contribute to the ongoing search for effective solutions to combat antibiotic resistance. Key studies demonstrating antibacterial effects against pathogens like Escherichia coli, Staphylococcus aureus, and multidrug-resistant strains are summarized. MOFs have exhibited antibacterial properties through controlled ion release and surface interactions. COFs have enhanced the efficacy of encapsulated antibiotics and displayed intrinsic antibacterial activity. Other nanomaterials, such as quantum dots, have generated reactive oxygen species, leading to microbial inactivation. This review aims to provide insights into these new classes of antibacterial materials and highlight them for addressing the global crisis of antibiotic resistance. KEY POINTS: • Nanomaterials show strong antibacterial effects against drug-resistant bacteria • Emerging solvents like ionic liquids offer novel solutions for bacterial resistance • MOFs and COFs enhance antibiotic efficacy, showing promise in combating resistance., Competing Interests: Declarations Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors. Conflict of interest The authors declare no competing interests., (© 2024. The Author(s).)

A facile, low-cost, and rapid method was developed for spectrofluorometric determination of tolmetin (TOL) using highly fluorescent (QY = 35%) cerium and nitrogen codoped carbon dots (Ce-NCDs) sensing platform prepared by one-step hydrothermal method. Owing to the severe overlap between TOL absorption and Ce-NCDs excitation spectra around 320 nm, TOL could attenuate the emission of Ce-NCDs at 407 nm through primary inner filter effect (IFE). This concentration dependent attenuation was linear between 2 and 10 μg/mL (r = 0.9993) with a limit of detection of 0.5 μg/mL. The sensor showed very good accuracy (% recovery = 98%-100%) and precision (%RSD < 2). The developed sensing strategy was successfully applied for TOL detection as an active pharmaceutical ingredient in pharmaceutical formulation and as a potential pollutant in environmental water samples, such as tap and river water, with acceptable recovery and considerable selectivity. Thus, the direct single-step spectrofluorometric determination of TOL was enabled without extensive processing or chemical derivatization., (© 2024 John Wiley & Sons Ltd.)

Letrozole is an anticancer medication prescribed for the management of estrogen receptor-positive breast cancer in postmenopausal women. Chronic pain is prevalent in patients receiving chemotherapy, leading to the use of adjuvant analgesics such as tramadol. This work introduces the first analytical approach for the concurrent quantification of letrozole and tramadol, two co-administered drugs, employing a rapid, highly sensitive, eco-friendly, and cost-effective first derivative synchronous spectrofluorimetric technique. The fluorescence of tramadol and letrozole was measured at wavelengths of 235.9 nm and 241.9 nm, respectively using a wavelength difference (Δλ) of 60.0 nm. The developed approach demonstrated exceptional linearity (r ˃ 0.999) within the specified concentration ranges for tramadol (10.0-1200.0 ng/mL) and letrozole (1.0-140.0 ng/mL). The results demonstrated that the proposed technique exhibits a high level of sensitivity, with detection limits of 0.569 and 0.143 ng/mL for tramadol and letrozole, respectively, indicating the good bioanalytical applicability. The within-run precisions, both intra-day and inter-day, for both analytes, were less than 0.71 % RSD. The developed approach was effectively applied to simultaneously estimate the mentioned drugs in their tablets and human plasma samples, achieving high percentage recoveries and low % RSD values. In order to assess the environmental sustainability of the developed approach, Analytical GREEnnessNNESS (AGREE) and the Green Analytical Procedure Index (GAPI) metric tools were employed. Both tools revealed that the developed approach is excellent green, suggesting its usage as an environmentally-friendly alternative for the routine assayof the investigated pharmaceuticals. The developed approach was validated according to the ICHQ2 (R1) requirements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Capillary electrophoresis (CE) is a powerful analysis technique with advantages such as high separation efficiency with resolution factors above 1.5, low sample consumption of less than 10 µL, cost-effectiveness, and eco-friendliness such as reduced solvent use and lower operational costs. However, CE also faces limitations, including limited detection sensitivity for low-concentration samples and interference from complex biological matrices. Prior to performing CE, it is common to utilize sample preparation procedures such as solid-phase microextraction (SPME) and liquid-phase microextraction (LPME) in order to improve the sensitivity and selectivity of the analysis. Recently, there have been advancements in the development of novel materials that have the potential to greatly enhance the performance of SPME and LPME. This review examines various materials and their uses in microextraction when combined with CE. These materials include carbon nanotubes, covalent organic frameworks, metal-organic frameworks, graphene and its derivatives, molecularly imprinted polymers, layered double hydroxides, ionic liquids, and deep eutectic solvents. The utilization of these innovative materials in extraction methods is being examined. Analyte recoveries and detection limits attained for a range of sample matrices are used to assess their effects on extraction selectivity, sensitivity, and efficiency. Exploring new materials for use in sample preparation techniques is important as it enables researchers to address current limitations of CE. The development of novel materials has the potential to greatly enhance extraction selectivity, sensitivity, and efficiency, thereby improving CE performance for complex biological analysis., (© 2024 Wiley‐VCH GmbH.)

The misuse of pregabalin has become a significant issue over the last decade. Consequently, there is a growing demand for a sensitive and selective method for its determination. In this study, an eco-friendly cobalt-doped carbon quantum dots (CQDs) have been fabricated and applied as nanoprobes for the fluorometric determination of pregabalin. The CQDs were synthesized through mixed doping with non-metallic atoms such as nitrogen and sulfur, and a metal ion, cobaltous ion, via a microwave-assisted method in just 1.5 min. The synthesized Co-NS-CQDs exhibited advantageous characteristics, including rapid response times, compatibility with various pH levels, exceptional detection limits, high sensitivity, and excellent selectivity. The Co-NS-CQDs exhibited a high quantum yield (55 %) relative to NS-CQDs (38 %), with blue emissive light at 438 nm. The assessment of pregabalin was based on its enhancement effect on the native fluorescence intensity of CQDs. The proposed method had a good linearity over the range of 25-250 µg/mL, with a limit of detection of 4.17 µg/mL and a limit of quantitation of 12.63 µg/mL, respectively. The prepared NS-CQDs have been successfully applied for the pregabalin determination in pharmaceutical capsules, with excellent % recovery (98-102 %). The greenness of the developed method has been investigated using different greenness metrics, in comparison with the reported RP HPLC method. The greenness characteristics of the method originated from the synthesis of CQDs, utilizing sustainable, readily available, and cost-effective starting materials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metal-organic frameworks (MOFs) are a fascinating family of crystalline porous materials made up of metal clusters and organic linkers. In comparison with other porous materials, MOFs have unique characteristics including high surface area, homogeneous open cavities, and permanent high porosity with variable shapes and sizes. For these reasons, MOFs have recently been explored as sorbents in sample preparation by solid-phase extraction (SPE). However, SPE requires large amounts of sorbents and suffers from limited contact surfaces with analytes, which compromises extraction recovery and efficiency. Dispersive SPE (D-SPE) overcomes these limitations by dispersing the sorbents into the sample, which in turn increases contact with the analytes. Miniaturization of the microextraction procedure, particularly the amount of sorbent reduces the amount consumed of the organic solvent and shorten the time required to attain the equilibrium state. This may explain the reported high efficiency and applicability of MOFs in dispersive micro SPE (D-µ-SPE). This method retains all the advantages of solid phase extraction while also being simpler, faster, cheaper, and, in some cases, more effective in comparison with D-SPE. Besides, D-µ-SPE requires smaller amounts of the sorbents which reduces the overall cost, and the amount of waste generated from the analytical process. In this review, we discuss the applications of MOFs in D-µ-SPE of various analytes including pharmaceuticals, pesticides, organic dyes from miscellaneous matrices including water samples, biological samples and food samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Viral diseases are a worldwide concern as some of them are associated with unexpectedly high mortality rates. Common viruses include e.g., Influenza virus, HIV, hepatitis viruses, and recently COVID-19. Many viral diseases are still incurable by conventional antiviral drugs. Moreover, the emergence of resistant viral strains has reinforced the search for other alternatives. In ancient times, herbal therapy was commonly used where medicinal formulations were created from various plants. In recent times, in vitro, in vivo, animal studies, and clinical trials have revealed the antiviral properties of these plants, sparking hope for the treatment of serious viral diseases. The present review aims to summarize studies that focus on medicinal plants available in Egypt with antiviral properties., Methods: The articles published in English between 1988 and 2022 and available in PubMed and Scopus databases with the relevant keywords were included., Results: Thirty-two plants in Egypt have met the criteria and possess in vitro or in vivo antiviral activity via different mechanisms. Only five of them; Camellia sinensis, Marine algae, Zizyphus spina-christi L., Trachyspermum Ammi, and Aloe Vera have been proven to be effective in vivo. For COVID-19, thirteen plants have shown efficacy against SARS-Cov-2 via different mechanisms including Camellia sinensis, Cinnamomum Verum, Punica granatum, Glycyrrhiza glabra, Zingiber officinale, Curcuma longa, Marine algae, Phlomis aurea oil, Solanum nigrum, Trachyspermum Ammi, Arum palaestinum, Aloe Vera, and Cyperus rotundus., Conclusion: This review summarizes the current scientific evidence on 32 medicinal plant species cultivated in Egypt that have demonstrated antiviral properties against various DNA and RNA viruses through in vitro and in vivo studies, highlighting their potential as prospective sources for the development of novel antiviral therapies. Further clinical research is still warranted to validate the effectiveness and safety of these plants as complementary treatment options for viral infections.

Multicomponent drugs are medications that combine two or more active pharmaceutical ingredients in a single dosage form. These dosage forms improve the patient compliance, reduce the risk of drug interactions, and simplify dosing regimens. However, quality control of these multicomponent dosage forms can be challenging, especially if the final product contains four or more ingredients that are active (comprise stabilizers, preservatives, excipients, and other components). This problem can be more pronounced if the excipients can interfere with the analysis. In this work, a stability indicating assay method was developed and validated (according to the ICH International Guidelines) for the simultaneous determination of hydroquinone (HQ), tretinoin (TRT), hydrocortisone (HCA), butylated hydroxytoluene (BHT), methyl paraben (MP) and propyl paraben (PP) in commercially available pharmaceutical creams. The proposed method is based on gradient elution using X-Bridge C18 (150 × 4.6 mm, 5 µm) column with a flow rate of 1 mL/min. The linear ranges (μg/mL) were 240-560 for HQ, 24-56 for MP, 132-308 for HCA, 6-14 for PP, 12-28 for BHT, 6.6-15 for TRT. During the validation process, the intra- and interday precision and trueness (evaluated as recovery) were found to be below 2.0% and between 100-102%, respectively. System suitability tests (SST) allow validating the herein proposed procedure specifically for pharmaceutical and industrial applications. SST test shows that the reported procedure fulfill with the Guidelines, allowing excellent separation of the analytes with very sensitive, accurate (precise and true) and reproducible quantitation of each analytes. The method was successfully applied in forced degradation studies of the six analytes. Specifically, acid degradation slightly affected HCA and BHT (91% recovery), while alkaline degradation drastically reduced HCA recovery (5.5%) and moderately affected BHT (85%). Photodegradation primarily influenced TRT quantity, and oxidative degradation intensified the BHT peak (130%)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study presents a stability indicating high-performance liquid chromatography HPLC method for the determination of cenobamate (CNB) in presence of its main impurity (CNB H-impurity) and degradation products. The chromatographic separation was carried out on a Thermo BDS Hypersil-C18 column (150 × 4.6 mm; 5 μm) with a mobile phase consisting of a 50:50 (%v/v) ratio of methanol and purified water. The flow rate was maintained at 1.0 mL. min - 1 . CNB was detected at 210 nm using a PDA detector. The column temperature was held at 40 °C.The retention time of the drug was found to be 3.2 min. Furthermore, the study investigates the degradation behavior of CNB under various stress conditions, including acidic, basic, oxidative, and light-induced degradation. The results indicate that CNB is particularly susceptible to basic degradation. Consequently, a comprehensive study of the basic degradation kinetics was conducted. The method was also successfully applied for the determination of CNB in its dosage form. The results also show that there is no co-elution from degradation products or excipients as indicated by the mass balance and peak purity values confirming the specificity of the proposed method and its applicability for routine analysis of CNB., (© 2024. The Author(s).)

A novel, simple, affordable, and reliable colorimetric paper-based analytical device (PAD) was developed for the point-of-use quality testing of ethanol-based hand sanitizers, mainly against adulteration by water. The principle was based on the novel solvatochromism of methylparaben (MPB)-Fe 3+ complex, where water is essential for complex formation and ethanol is necessary for MPB solubility. The intensity of the formed violet color, measured at 528 nm, showed a good correlation ( R 2 = 0.996) with the percentage water in the reaction media over a range from 40% to 100% (0-60% ethanol), with excellent accuracy and precision as indicated by the percent recovery within 100.00% ± 2% and %RSD of <2%. A PAD was prepared by the sequential immobilization of Fe 3+ ions and MPB on chitosan-modified filter paper. The developed PAD was successfully applied for the quality testing of ethanol-based hand sanitizers using an established color index, where clearly distinct colors were observed as a function of the percentage ethanol (0-100%). The developed test strips could achieve on-site lab-quality results without expensive or sophisticated instruments using a few milligrams of FeCl 3 and MPB in addition to regular filter paper. Accordingly, it can be used as a test strip for the quality checking of ethanol-based hand sanitizers by end users., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have influenced this work., (This journal is © The Royal Society of Chemistry.)

The increasing antibiotic resistance towards a panel of microorganisms is one of the public health concerns. For this reason, the search for alternatives to the widely used antibiotic has been undertaken. In the era of sustainable chemistry, deep eutectic solvents (DESs) have emerged as promising antimicrobial agents. These solvents possess several advantages such as low volatility, low flammability, ease of preparation, and typically low cost of production. These properties make DES suitable for various applications, including extraction of biomolecules and preparation of cosmetics. Natural DESs (NADESs) are special category of DESs prepared from natural sources, which matched the recent trends of leaning back to nature, and decreasing dependence on synthetic precursors. NADES can be prepared by heating and stirring, freeze-drying, evaporation, grinding, and ultrasound-assisted and microwave-assisted synthesis. Utilizing NADESs as an alternative to traditional antibiotics, which become ineffective over time due to bacterial resistance, holds great promise for these reasons. This review aims to discuss the antimicrobial properties of multiple NADESs, including antibacterial and antifungal activities. To the best of our knowledge, this review is the first literature survey of the antimicrobial activities of NADESs. KEY POINTS: • Natural deep eutectic solvents are promising antimicrobial alternative to antibiotics • NADES holds high potential for their activity against bacterial resistance • NADES have also substantial antifungal activities., (© 2024. The Author(s).)

Heparin (HEP) is one of the oldest anticoagulant drugs that currently still in widespread clinical use. It lacks chromophore and not easily derivatized due to its hydrophilic nature. In this work we developed a green, selective, and sensitive fluorescence sensor for detection of HEP in its injection dosage forms. The sensor is composed of nitrogen and sulfur co-doped carbon quantum dots (N,S-CDs) semi quenched by Fe 3+ . The N,S-CDs were prepared using microwave assisted pyrolysis in 3.5 min and exhibited high emission at 425 nm after excitation at 350 nm with high quantum yield of 96%. Owing to the anionic nature of HEP, it could compete with N,S-CDs for Fe 3+ complexation resulting in turning-on the quenched fluorescence. This fluorescence enhancement was linear over a concentration range between 6 and 20 μg/mL (R 2  = 0.99) with a limit of detection of 1.41 µg/ml. The accuracy and precision of the proposed sensor were indicated by percentage recovery values between 98% -102% and %RSD less than 2, respectively. Furthermore, the proposed sensor was successfully applied for determination of HEP in injection dosage form. The developed sensor showed excellent greenness on analytical eco-scale (score 93%) and GAPI scale., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Toxocariasis is a zoonosis that represents a serious threat to public health particularly in tropical and subtropical areas. Currently, albendazole, the most effective drug for treating visceral toxocariasis, shows moderate efficacy against the larvae in tissues and has some adverse effects. Artemether is an antiparasitic drug mainly used in the treatment of malaria and showed effectiveness against numerous helminthic infections. Besides, it possesses potent anti-inflammatory, antiapoptotic, antifibrotic, and neuroprotective properties. Thus, the study's aim was to investigate artemether's effects in comparison with albendazole on the therapeutic outcome of experimental toxocariasis. For this aim, 140 laboratory-bred mice were divided into four main groups: uninfected control, treatment control, albendazole-treated, and artemether-treated groups. The treatment regimens were started at the 15 th dpi (early treatment), and at the 35 th dpi (late treatment). The effectiveness of treatment was determined by brain larval count, histopathological, immunohistochemical, and biochemical examination. Artemether showed more effectiveness than albendazole in reducing brain larval counts, markers of brain injury including NF-κB, GFAP, and caspase-3, the diameter and number of hepatic granulomas, hepatic oxidative stress, hepatic IL-6, and TG2 mRNA, and pulmonary inflammation and fibrosis. The efficacy of artemether was the same when administered early or late in the infection. Finally, our findings illustrated that artemether might be a promising therapy for T. canis infection and it could be a good substitution for albendazole in toxocariasis treatment.

Introduction: The conventional processes of drug discovery are too expensive, timeconsuming and the success rate is limited. Searching for alternatives that have evident safety and potential efficacy could save money, time and improve the current therapeutic regimen outcomes., Methods: Clinical phytotherapy implies the use of extracts of natural origin for prophylaxis, treatment, or management of human disorders. In this work, the potential role of common Fig ( Ficus carica ) in the management of COVID-19 infections has been explored. The antiviral effects of Cyanidin 3-rhamnoglucoside which is abundant in common Figs have been illustrated on COVID-19 targets. The immunomodulatory effect and the ability to ameliorate the cytokine storm associated with coronavirus infections have also been highlighted. This work involves various computational studies to investigate the potential roles of common figs in the management of COVID-19 viral infections., Results: Two molecular docking studies of all active ingredients in common Figs were conducted starting with MOE to provide initial insights, followed by Autodock Vina for further confirmation of the results of the top five compounds with the best docking score., Conclusion: Finally, Molecular dynamic simulation alongside MMPBSA calculations were conducted using GROMACS to endorse and validate the entire work., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Biomass and biowastes stand as sustainable and cost-effective environmentally benign alternative feedstock. Chitosan is a biocompatible, bioactive, and biodegradable biopolymer derived from chitin to achieve eight aspects out of the 12 green chemistry principles. Chitosan got significant attention in several fields including chemical analysis, in addition to chemical functionally, which enabled its use as adsorbent and its structural crosslinking using various crosslinkers. The physicochemical, technological, and optical properties of chitosan have been extensively exploited in analysis. Mainly, deacetylation degree and molecular weight are controlling its properties and hence controlling its functions. This review presents a structure, properties, and functions relationships of chitosan. It also aims to provide an overview of the different functions that chitosan can serve in each analytical technique such as supporting matrix, catalyst…etc. The contribution of chitosan in improving the ecological performance is discussed in each technique.

The recently introduced gadolinium-based magnetic ionic liquid (Gd-MIL) has been exploited as an extractant in dispersive liquid-liquid microextraction (DLLME) for preconcentration of ivermectin (IVR) from water samples followed by analysis using reversed-phase HPLC with UV detection at 245 nm. The utilized Gd-MIL extractant is hydrophobic with markedly high magnetic susceptibility. These features result in an efficient extraction of the lipophilic analyte and facilitate the phase separation under the influence of a strong magnetic field, thus promoting the method sensitivity and increasing the potential for automation. To maximize the IVR enrichment by DLLME, the procedure was optimized for extractant mass, dispersive solvent type/volume, salt addition and diluent pH. At optimized conditions, an enrichment factor approaching 70 was obtained with 4.0-mL sample sizes. The method was validated in terms of accuracy, precision, specificity and limit of quantitation. The method was successfully applied to the determination of IVR in river water samples with a mean relative recovery of 97.3% at a spiked concentration of 400 ng/mL. Compared with other reported methods, this approach used a simpler procedure with improved precision, lower amounts of safer solvents and a short analysis time., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A straightforward, rapid, and selective fluorescent probe for determination of tilmicosin has been developed based on novel nitrogen and sulfur co-doped CDs (NS-CD). The NS-CDs were synthesized, for the first time, through green, simple one step microwave pyrolysis in only 90 s using glucose as carbon source and l-cysteine as nitrogen and sulfur source. This proposed synthesis method was energy-efficient and resulted in NS-CDs with high production yield (54.27 wt%) and narrow particle size distribution. Greenness of NS-CDs synthesis method was assessed using EcoScale and was proven to be excellent green synthesis. The produced NS-CDs were applied as a nano-probe for determination of tilmicosin in its marketed formulation and milk based on dynamic quenching mechanism. The developed probe showed a good performance for tilmicosin detection in marketed oral solution and pasteurized milk and linearity range of 9-180 μM and 9-120 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The study reports the development of a high-performance liquid chromatography/diode array detection method to measure the levels of nirmatrelvir and ritonavir in human plasma. These two antiviral medications are used for the treatment of COVID-19 and are marketed as Paxlovid ® . The method employed sugaring-out induced homogeneous liquid-liquid microextraction to improve sensitivity. Optimization of the method was performed using the one variable at a time approach by adjusting several factors such as type of sugar, extractant, amount of sugar, volume of extractant, and pH of the aqueous sample to achieve the highest efficiency. The developed method was validated according to the Food and Drug Administration guidelines and demonstrated good linearity, accuracy, and precision. The range of linearity was from 1000 to 20,000 ng/mL for nirmatrelvir and 200 to 20,000 ng/mL for ritonavir with correlation coefficient values of 0.998 and 0.996, respectively. Selectivity studies revealed that no others peaks appeared in the retention times of the studied drugs. The stability of nirmatrelvir and ritonavir were also investigated through short term and three cycles of freeze-thaw, and both drugs were found stable. This analytical method could be useful for monitoring drug concentrations in patients undergoing treatment with these medications for COVID-19. In this work, for the first time, SULLME was used for the sensitive determination of nirmatrelvir and ritonavir in biological fluids. The developed method was able to determine both drugs in therapeutic levels with no need to sophisticated techniques like LC-MS. In addition to that, SULLME is considered a simple and green sample preparation in comparison with conventional sample preparation methods., (© 2023. The Author(s).)

Flavonoids are plant-derived compounds that have several health benefits, including antioxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. Quercetin is a flavonoid that is widely present in various fruits, vegetables, and drinks. Accurate determination of quercetin in different samples is of great importance for its potential health benefits. This review, is an overview of sample preparation and determination methods for quercetin in diverse matrices. Previous research on sample preparation and determination methods for quercetin are summarized, highlighting the advantages and disadvantages of each method and providing insights into recent developments in quercetin sample treatment. Various analytical techniques are discussed including spectroscopic, chromatographic, electrophoretic, and electrochemical methods for the determination of quercetin and its derivatives in different samples. UV-Vis (Ultraviolet-visible) spectrophotometry is simple and inexpensive but lacks selectivity. Chromatographic techniques (HPLC, GC) offer selectivity and sensitivity, while electrophoretic and electrochemical methods provide high resolution and low detection limits, respectively. The aim of this review is to comprehensively explore the determination methods for quercetin and quercetin glycosides in diverse matrices, with emphasis on pharmaceutical and biological samples. The review also provides a theoretical basis for method development and application for the analysis of quercetin and quercetin glycosides in real samples.

Solid phase microextraction (SPME) is considered simple, ecofriendly, sustainable, cost-effective and timesaving sample preparation mode in comparison with other sample preparation procedures. The researchers always try to develop new sorbents with higher surface area in comparison with other conventional sorbents aiming to enhance the extraction efficiency. In this work for the first time, a comparative study was performed between Ca-BTC MOF (1,3,5-benzenetricarboxylic acid, BTC; metal-organic framework, MOF) and a hybrid Ca-BTC-MCC MOF (microcrystalline cellulose, MCC) by using as model compounds seven drugs with different physicochemical properties. The evaluation of the extraction efficiency of both sorbents were obtained by means of an HPLC/DAD instrument configuration in reversed phase mode under isocratic elution mode. The results indicate that Ca-BTC MOF showed superior extraction efficiency than Ca-BTC-MCC MOF in the case of all analytes except nirmatrelvir and ritonavir. The results highlight that not only the surface area of adsorbents controlled the adsorption capacity, but also other factors have a role in extraction efficiency including morphology of adsorbent and physico-chemical properties of the analytes. It is worth mentioning that this is the first time that a comparative study was performed between Ca-BTC MOF and Ca-BTC-MCC MOF hybrid material., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus's worldwide pandemic has highlighted the urgent need for reliable, quick, and affordable diagnostic tests for comprehending and controlling the epidemic by tracking the world population. Given how crucial it is to monitor and manage the pandemic, researchers have recently concentrated on creating quick detection techniques. Although PCR is still the preferred clinical diagnostic test, there is a pressing need for substitutes that are sufficiently rapid and cost-effective to provide a diagnosis at the time of use. The creation of a quick and simple POC equipment is necessary for home testing. Our review's goal is to provide an overview of the many methods utilized to identify SARS-CoV 2 in various samples utilizing portable devices, as well as any potential applications for smartphones in epidemiological research and detection. The point of care (POC) employs a range of microfluidic biosensors based on smartphones, including molecular sensors, immunological biosensors, hybrid biosensors, and imaging biosensors. For example, a number of tools have been created for the diagnosis of COVID-19, based on various theories. Integrated portable devices can be created using loop-mediated isothermal amplification, which combines isothermal amplification methods with colorimetric detection. Electrochemical approaches have been regarded as a potential substitute for optical sensing techniques that utilize fluorescence for detection and as being more beneficial to the Minimizing and simplicity of the tools used for detection, together with techniques that can amplify DNA or RNA under constant temperature conditions, without the need for repeated heating and cooling cycles. Many research have used smartphones for virus detection and data visualization, making these techniques more user-friendly and broadly distributed throughout nations. Overall, our research provides a review of different novel, non-invasive, affordable, and efficient methods for identifying COVID-19 contagious infected people and halting the disease's transmission., Competing Interests: The authors declare no competing interest., (© 2023 The Author(s).)

Google Trends has been extensively used in different sectors from finance to tourism, the economy, fashion, the fun industry, the oil trade, and healthcare. This scoping review aims to summarize the role of Google Trends as a monitoring and a predicting tool in the COVID-19 pandemic. Inclusion criteria for this scoping review were original English-language peer-reviewed research articles on the COVID-19 pandemic conducted in 2020 using Google Trends as a search tool. Articles that were in a language other than English, were only in abstract form, or did not discuss the role of Google Trends during the COVID-19 pandemic were excluded. According to these criteria, a total of 81 studies were included to cover the period of the first year after the emergence of the crisis. Google Trends can potentially help health authorities to plan and control pandemics earlier and to decrease the risk of infection among people., (© The Author(s) 2023. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A simple, fast, and ecofriendly spectrofluorometric method was developed and validated for determination of mono sodium glutamate (MSG). The method depended on the reaction between MSG and iron (III) salicylate based on ligand exchange mechanism. Addition of MSG turned-on the fluorescent response of iron (III) salicylate at λ em 411 nm. Reaction conditions including reagent concentration, pH, and time were optimized. The method was validated regarding the ICH guidelines. The method determined MSG within the linearity range of 25-250 µM with a coefficient of determination of 0.9967 and a calculated limit of detection of 1.73 µM. Furthermore, the developed method was successfully applied for the determination of MSG in food preparation (instant noodles). The results were compared to those obtained by a published HPLC method using t-test and F-test at 95% confidence interval; no statistically significant difference was found. Based on the analytical Eco-scale and the green analytical procedure index (GAPI), the developed method was assessed to be greener than the published HPLC method. The developed method offered advantages over other spectrophotometric reported methods and was convenient for routine determination of MSG in foodstuffs., (© 2023. The Author(s).)

The effect of hydrophilic/lipophilic balance (HLB) of polyoxyethylene ethers of different chain lengths on the microporogenic properties of the Brij surfactants has been studied. The objective of this work is to help better understand the role of each porogen and to set criteria for selecting the proper non-ionic surfactant, based on the HLB value. Seven recipes of different porogen compositions were first prepared and the highest efficiency was achieved using decane/decanol/dodecanol mixture with Brij® 30. Then, four other Brij surfactants covering the entire HLB scale were tested, and the prepared monoliths were characterized by SEM, BET, FT-IR and chromatography. The results showed that increasing the HLB from 9.72 to 18.84 was accompanied by an increase in monolith density and surface areas. The optimum HLB range was found to be 10 to 15. Surfactants of lower HLB formed either nonporous or less efficient columns, while those of higher HLB formed non-permeable columns. Adjusting the HLB was possible by mixing surfactants of different HLB. The prepared monoliths could be used in the isocratic mode with a mobile phase consisting of a mixture of ACN and water (20:80, v/v) at a flow rate of 1.5 μL min -1 to separate five sulfa drugs. The separation results showed that the elution order of the compounds correlated with their lipophilicity, with sulfamerazine (logp = 0.52) being the first to elute, and sulfaquinoxoline (logp=1.70) being the most retained. The asymmetry factors of the separated compounds ranged between 1.18 and 1.25, and the resolution was found to be in the range 2.92-7.80. The prepared monoliths could be also successfully separate a mixture of four different nonsteroidal anti-inflammatory drugs and a mixture of four benzoic acid derivatives. This work assists in optimizing the surfactant-based porogenic mixture to meet the desired porosity, surface area, morphology and chromatographic separation requirements., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

A simple and eco-friendly microwave method was applied for the preparation of highly fluorescent nitrogen and sulfur co-doped carbon quantum dots (NS-CQDs) and used for the determination of ascorbic acid (ASC) in pharmaceutical dosage forms. The prepared NS-CQDs had bright blue fluorescence at a maximum emission wavelength of 440 nm, after excitation with 350 nm, with a quantum yield of 62.5 %. The developed NS-CQDs were prepared from citric acid and l-cysteine in one minute. The native fluorescence of NS-CQDs was quenched by ferric ions due to the formation of non-fluorescent CQDs/ Fe 3+ complex. The quenched fluorescence could be restored by the addition of ASC due to the reducing properties of ASC which converts Fe 3+ to Fe 2+ . The method was found linear over the concentration range of 2.0-100 μg/mL, with a limit of detection was 0.6 μg/mL and a coefficient of determination of 0.9965. The proposed method was cross-validated and statistically compared with a reported HPLC method. The results indicated that the developed method was greener, according to the analytical eco-scale and the green analytical procedure index (GAPI). The prepared NS-CQDs were used for spectrofluorometric determination of ASC in pharmaceutical dosage forms, with percentage recoveries ranging between 98 and 102 %, and relative standard deviations less than 2 %. The method was easy, rapid, reliable, and sensitive and did not require expensive reagents or sophisticated equipment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Ascorbic acid (ASC; vitamin C) is a weak chromophore, so its presence cannot be determined directly by spectrophotometry., Objective: This work aims to develop and validate a simple and ecofriendly analytical method for the determination of ASC concentration based on the reaction of ASC with the metal complex, ferric salicylate., Methods: The visible absorbance of ferric salicylate was found to be inversely proportional to the concentration of ASC. The possible mechanism of the reaction between ASC and ferric salicylate was investigated: ferric salicylate was found to be reduced by ASC under the applied experimental conditions. Different parameters that may affect the reaction were also investigated: ferric salicylate concentration, pH, ionic strength, and the time of reaction. The optimum concentration of ferric salicylate was found to be 1000 µM and the optimum pH was 5.5. The developed method was validated according to International Conference on Harmonization (ICH) guidelines., Results: The linearity range of the developed method was 5-70 µg/mL and the correlation coefficient was 0.9994. The limits of detection and quantitation were 0.38 µg/mL and 1.16 µg/mL, respectively. The method was successfully applied to the determination of ASC concentration in commercial Ruta-C60® tablets. The mean recovery ± standard deviation was found to be 101.10 ± 0.70%. The results were statistically compared to those obtained by a reported HPLC method. Good agreement was observed., Conclusion: The developed method is simple, fast, cost-effective, and suitable for routine pharmaceutical analysis of ASC., Highlights: The developed method is more sensitive than the other spectrophotometric methods reported for determination of ASC., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The coronavirus pandemic is a worldwide hazard that poses a threat to millions of individuals throughout the world. This pandemic is caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which was initially identified in Wuhan, China's Hubei provincial capital, and has since spread throughout the world. According to the World Health Organization's Weekly Epidemiological Update, there were more than 250 million documented cases of coronavirus infections globally, with five million fatalities. Early detection of coronavirus does not only reduce the spread of the virus, but it also increases the chance of curing the infection. Spectroscopic techniques have been widely used in the early detection and diagnosis of COVID-19 using Raman, Infrared, mass spectrometry and fluorescence spectroscopy. In this review, the reported spectroscopic methods for COVID-19 detection were discussed with emphasis on the practical aspects, limitations and applications., (© 2022. The Author(s).)

Fixed dose combinations of glutathione and ascorbic acid are marketed due to the synergetic effect of glutathione, which regenerates ascorbic acid, potentiates its action and prolongs its antioxidant potential. In this work, glycerol was introduced for the first time as a green mobile phase modifier for liquid chromatographic determination of glutathione and ascorbic acid in pharmaceutical tablets. The viscosity barrier was overcome by using water as a co-fluidifying solvents and by controlling the column temperature. Compared with methanol and acetonitrile, glycerol could result in better peak shapes and superior system suitability. To explore the retention process, free energy and enthalpy-entropy compensation were calculated for both glutathione and ascorbic acid. The chromatographic conditions were optimized using factorial design with the aid of Minitab 17® Software. The method was successfully validated according to the guidelines of the International Conference on Harmonization Q2 (R1) and was found linear in the range of 1 μg/mL to 300300 μg/mL for both drugs. The method was evaluated in terms of its greenness and then compared to the reported method. Glycerol has several advantages over commonly employed mobile phase modifiers, such as the high safety, the low UV cut-off point, low flammability, low volatility, the green features, and the biodegradability. This work paves the way for more applications of glycerol in green liquid chromatography., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A simple, fast, and green one-step microwave pyrolysis approach was proposed for the synthesis of highly fluorescent nitrogen/sulfur-doped carbon dots (NS-CDs). The proposed NS-CDs were prepared in only one minute from citric acid and thiosemicarbazide. In the presence of Cu 2+ , the fluorescence of NS-CDs was significantly quenched ("turn off") through the formation of a non-fluorescent NS-CDs/Cu 2+ complex. This designed sensor could be applied for label-free determination of vildagliptin based on the competition between vildagliptin and the functional groups on NS-CDs for Cu 2+ complexation, and hence NS-CD fluorescence recovery ("turn on"). Under the optimized conditions, the developed probe (NS-CDs/Cu 2+ ) demonstrated a good sensing performance for vildagliptin with linearity in the range of 45-240 μM and a detection limit of 13.411 μM. Owing to its sensitivity, this sensor was successfully applied for vildagliptin determination in human urine samples., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A simple stability-indicating reversed-phase high-performance liquid chromatography method has been developed for determination of elobixibat in presence of its potential impurities and degradation products. The chromatographic separation was carried on a Thermo scientific Base Deactivated Silica BDS Hypersil-C18 (150 × 4.6 mm; 5 μm) column using a mobile phase of acetonitrile and phosphate buffer (25 mM, pH 2.5) in a ratio of (70:30, v/v). The experimental conditions were accurately investigated, and the method was validated according to ICH guidelines Q2 (R1). The drug was subjected to various stress conditions including acidic, basic, oxidative, and photolytic conditions. The method successfully separates the drug from the three reported impurities and different degradants. The method was also successfully applied for the determination of elobixibat in laboratory prepared tablets (5.0 mg). Analysis shows no interference from excipients and degradation products. The method was also applied for performing in vitro dissolution testing of elobixibat laboratory prepared tablets. Since elobixibat is recently introduced into the market, there are no previous stability studies and no reported analytical methods for its determination. Thus, this study presents a validated and selective method that can be effectively employed in routine quality control studies., (© 2022 Wiley-VCH GmbH.)

Favipiravir is a potential antiviral medication that has been recently licensed for Covid-19 treatment. In this work, a gadolinium-based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid-liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd-magnetic ionic liquid (MIL) and 150 μl of tetrahydrofuran. The Gd-based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 10 5  ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma., (© 2022 John Wiley & Sons, Ltd.)

A vortex-assisted dispersive liquid-liquid microextraction (DLLME) method, mated to chemometrics and combined with HPLC/UV detection was optimized and validated for enrichment and determination of repaglinide in environmental samples using nateglinide as an internal standard (IS). A phosphate buffer (10 mM, pH 2.5): acetonitrile (45:55, v/v) was used as a mobile phase with a flow rate of 1 mL/min in an isocratic elution mode. Chemometrics-assisted optimization was performed using a quadratic integrated D-optimal design. The developed model assessed the statistical significance of the independent variables and their interactions to attain the optimum conditions revealing that extractant type, extractant volume and pH are the most influential factors. Optimization of the extraction procedures was performed with the aid of Design Expert 8® software, which suggested 58 different experiments. The optimal conditions were 30 µL of 1-octanol as extractant, 100 µL of acetonitrile as a disperser at pH 8. Under the optimized conditions, the method showed linearity over the range of 1-100 ng/mL with a limit of detection of 0.4 ng/mL. The accuracy, the intra- and inter-day precision were assessed, the %recoveries were found to be between 98.48 and 100.81% with %RSD lower than 1.3. Using chemometrics in method optimization helped achieve the maximum possible enrichment with the least effort, time, and reagents while considering all possible interactions between variables., (© 2022. The Author(s).)

Ascorbic acid has recently been extensively used due to its role in the management of COVID-19 infections by stimulating the immune system and triggering phagocytosis of the corona virus. The currently used spectrofluorometric methods for determination of ascorbic acid require using derivatizing agents or fluorescent probes and suffer from a number of limitations, including slow reaction rates, low yield, limited sensitivity, long reaction times and high temperatures. In this work, we present a highly sensitive spectrofluorometric method for determination of ascorbic acid by switching-on the fluorescence of salicylate in presence of iron (III) due to a reduction of the cation to iron (II). The addition of ascorbic acid resulted in a corresponding enhancement in the fluorescence intensity of iron (III)-salicylate complex at emission wavelength = 411 nm. The method was found linear in the range of 1-8 µg/mL with a correlation coefficient of 0.9997. The limits of detection and quantitation were 0.035 µg/mL and 0.106 µg/mL, respectively. The developed method was applied for the determination of ascorbic acid in the commercially available dosage form; Ruta C60® tablets. The obtained results were compared with those obtained by a reported liquid chromatographic method at 95% confidence interval, no statistically significant differences were found between the developed and the reported methods. Yet, the developed spectrofluorometric method was found markedly greener than the reference method, based on the analytical Eco-scale and the green analytical procedure index. This work presents a simple, rapid and sensitive method that can possibly be applied for determination of ascorbic acid in pharmaceuticals, biological fluids and food samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Poly(styrene- co -divinylbenzene)-based monoliths were prepared from the polymerisation of water-in-monomer high internal phase emulsions, where the water-soluble monomers acrylamide (AAm) or poly(ethylene glycol) diacrylate (PEGDA) ( M w 258) were also included in the 90 vol% internal phase. Both AAm and PEGDA were found to act as co-surfactants, resulting in the obtainment of monoliths with greater homogeneity in some cases. As a result these materials demonstrated significantly improved chromatographic performance for the separation of a standard mixture of proteins using reversed-phase liquid chromatography, in comparison to monoliths prepared with no internal phase monomer. In particular, the columns grafted with PEGDA were capable of separating a more complex mixture consisting of seven components. The inclusion of monomers in the internal phase also allowed for the functionalisation of the monolith's surface where the degree of polymerisation that occurred in the internal phase, which was governed by the monomer content in the internal phase and initiation location, determined whether polymeric chains or a hydrogel were grafted to the surface. A monolith grafted with AAm was also found to be capable of retaining polar analytes as a result of the increase in surface hydrophilicity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

An environmentally-friendly, selective and rapid turn off-on fluorescent probe for both copper (Cu 2+ ) and etidronate disodium (ETD) detection was derived from nitrogen/sulfur co-doping of carbon dot (N,S-CD). The N,S-CDs were produced, for first time, through microwave-assisted pyrolysis in only 60 s using readily accessible and cheap precursors (citric acid and thiosemicarbazide). The proposed synthesis method resulted in N,S-CDs with narrow particle size distribution, high product yield (64.38 wt%) and high doping efficiency (N, 28.56% and S, 8.47%). The turn off-on sensor was developed after demonstrating the ability of Cu 2+ to quench fluorescence of the produced CDs and probable fluorescence restoration through complexation of Cu 2+ by the bisphosphonate group of ETD. The developed sensor showed a good performance for Cu 2+ and ETD detection with a linear range of 5-125 μM and 30-210 μM, respectively. This developed platform could be applied for routine analysis of Cu 2+ and ETD with good recoveries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This work presented a novel racemic imprinting process employing the chiral properties of chitosan monomer. The preparation of racemic ketoprofen (RS-KTP) imprinted polymer (RS-MIP) was conducted using glutaraldehyde as a crosslinker. The nature of elution solvent affected the % desorption ratio suggesting a heterogenous nature of the formed binding sites. Good imprinting was indicated by an imprinting factor of 3.50 for S-KTP. The enantioselectivity of the RS-MIP was indicated by enantioselectivity coefficient of 2.31 and % enantiomeric excess (%ee) of 28.55%. A SPE cartridge packed with RS-MIP enabled resolution of RS-KTP using gradient elution solvent system. Scatchard plot revealed two binding sites types of different affinity towards S-KTP and density observed for the RS-MIP. The binding capacity of RS-MIP showed observed dependence on the % ee of S-KTP indicating its enantioselectivity. The success of using racemic template for the preparation of enantioselective MIP brings a new possibility to achieve enantioseparation of racemic mixtures having very expensive or unavailable pure enantiomers., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Favipiravir is an antiviral drug that was recently approved for the management of COVID-19 infection. Aim: This work aimed to develop a new method, using sugaring-out induced homogeneous liquid-liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma. Materials & methods: The optimum extraction conditions were attained using 500 μl of tetrahydrofuran as an extractant and 1400 mg of fructose as a phase-separating agent. Results: The developed method was validated according to the US FDA bioanalytical guidelines and was found linear in the range of 25-80,000 ng/ml with a correlation coefficient of 0.999. Conclusion: These results showed that the developed method was simple, easy, valid and adequately sensitive for determination of favipiravir in plasma for bioequivalence studies.

Aluminum (Al) is an abundant metal with wide application in our daily lives including medicine, industry, cosmetics, and packaging. After entrance to the body, aluminum binds to transferrin and reaches different tissues. Al is a metalloestrogen that can lead to oxidative stress (OxS) and endocrine disruption. No detailed study can be found addressing the effect of Al on the ovary and granulosa cells (GCs). In this study, the focus is on the treated ovaries and GCs of NMRI mice exposed to low, middle, and high doses of aluminum chloride (AlCl 3 ) via in vitro and in vivo assays. The steroidogenic, proliferative, apoptotic, and autophagic-related genes were examined. Up-regulated expression of steroidogenic and proliferative genes was detected. The observed apoptotic and autophagic genes had variable expression. Interrupted ovarian structure, disrupted folliculogenesis, presence of Call-Exner bodies, overexpression of steroidogenic gene, and unbalanced apoptosis/autophagy and proliferation resembled features of granulosa cell tumor (GCT)., (Copyright © 2021. Published by Elsevier B.V.)

Favipiravir is a promising antiviral agent that has been recently approved for treatment of COVID-19 infection. In this study, a menthol-assisted homogenous liquid-liquid microextraction method has been developed for favipiravir determination in human plasma using HPLC/UV. The different factors that could affect the extraction efficiency were studied, including extractant type, extractant volume, menthol amount and vortex time. The optimum extraction efficiency was achieved using 300 µL of tetrahydrofuran, 30 mg of menthol and vortexing for 1 min before centrifuging the sample for 5 min at 3467g. Addition of menthol does not only induce phase separation, but also helps to form reverse micelles to facilitate extraction. The highly polar favipiravir molecules would be incorporated into the hydrophilic core of the formed reverse micelle to be extracted by the non-polar organic extractant. The method was validated according to the FDA bioanalytical method guidelines. The developed method was found linear in the concentration range of 0.1 to 100 µg/mL with a coefficient of determination of 0.9992. The method accuracy and precision were studied by calculating the recovery (%) and the relative standard deviation (%), respectively. The recovery (%) was in the range of 97.1-103.9%, while the RSD (%) values ranged between 2.03 and 8.15 %. The developed method was successfully applied in a bioequivalence study of Flupirava® 200 mg versus Avigan® 200 mg, after a single oral dose of favipiravir administered to healthy adult volunteers. The proposed method was simple, cheap, more eco-friendly and sufficiently sensitive for biomedical application., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Liquid-liquid extraction is a widely used technique of sample preparation in biomedical analysis. In spite of the high pre-concentration capacities of liquid-liquid extraction, it suffers from a number of limitations including time and effort consumption, large organic solvent utilization, and poor performance in highly polar analytes. Homogeneous liquid-liquid extraction is an alternative sample preparation technique that overcomes some drawbacks of conventional liquid-liquid extraction, and allows employing greener organic solvents in sample treatment. In homogeneous liquid-liquid extraction, a homogeneous phase is formed between the aqueous sample and the water-miscible extractant, followed by chemically or physically induced phase separation. To form the homogeneous phase, aqueous samples are mixed with water-miscible organic solvents, water-immiscible solvents/cosolvents, surfactants, or smart polymers. Then, phase separation is induced chemically (adding salt, sugar, or buffer) or physically (changing temperature or pH). This mode is rapid, sustainable, and cost-effective in comparison with other sample preparation techniques. Moreover, homogeneous liquid-liquid extraction is more suitable for the extraction of delicate macromolecules such as enzymes, hormones, and proteins and it is more compatible with liquid chromatography with tandem mass spectrometry, which is a vital technique in metabolomics and proteomics. In this review, the principle, types, applications, automation, and technical aspects of homogeneous liquid-liquid extraction are discussed., (© 2021 Wiley-VCH GmbH.)

The effect of adding ethoxylated sorbitan ester surfactants (Tweens®) to poly(ethylene glycol) diacrylate-based monolithic recipes was investigated. Five different Tweens® have been evaluated to investigate the exact role of non-ionic surfactants in poly(ethylene glycol) diacrylate-based monolith preparations. These monoliths were characterized by scanning electron microscopy, infrared spectroscopy, and nitrogen physisorption analysis. Different morphological features, and surface areas were observed when different types of Tween® were included in the recipe; Tween® 20 and 85 showed small globules, while Tween® 40, 60 and 80 exhibited larger globular structures with different sizes and degrees of coalescence. The different Tween®-based monoliths were investigated for the chromatographic separation of mixtures consisting of hydroxybenzoic acids and alkylbenzenes. These columns were mechanically stable, except for Tween® 80. The highest methylene selectivity and the best overall performance were achieved by Tween® 60. The efficiency was increased by increasing the concentration of the Tween® 60 and the amount of poly(ethylene glycol) diacrylate M n 700 in the recipes up to 30 wt%, each. Further increases in either Tween® 60 or poly(ethylene glycol) diacrylate M n 700 led to formation of non-permeable columns. The optimized column was successfully used for separation of mixtures of nonsteroidal anti-inflammatory and sulfa drugs, with a maximum efficiency of 60,000 plates/m., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Miniaturization of liquid-liquid extraction is a growing field of sample preparation to reduce solvent consumption, protect the environment, and preserve operators' health. In this work, four different modes of liquid-liquid microextraction have been compared including dispersive liquid-liquid microextraction, binary and ternary salting-out, and sugaring-out induced liquid-liquid microextraction. The extraction efficiency was evaluated by the enrichment factors of 14 different drugs from three pharmacological classes. Compared with the other modes, sugaring-out induced liquid-liquid microextraction was found to be the most efficient and, thus, it was applied for sample preparation of the antivirals in human plasma. Method optimization was performed using response surface methodology for the sugar type and amount (in mg), the sample pH, the equilibration time (in min), and the extractant volume (in µL). The method was then validated and found linear in the concentration range of 0.10-10 µg/mL for daclatasvir, 0.05-10 µg/mL for velpatasvir, and 0.20-10 µg/mL for ledipasvir, with correlation coefficients in the range 0.996-0.999. These results shows that sugaring-out induced liquid-liquid microextraction could be a more efficient microextraction mode for preparation of biological samples. Compared with other types of microextraction, sugaring-out induced liquid-liquid microextraction is greener, simpler, and cost-effective, with less tendency to affect the sample pH., (© 2021 Wiley-VCH GmbH.)

The coronavirus pandemic could be the most threatening outbreak in the twenty-first century. According to the latest records of world health organization, more than 130 millions have been infected by COVID-19, with more than 2.9 million reported deaths. Yet, there is no magic cure for treatment of COVID-19. The concept of drug repurposing has been introduced as a fast, life-saving approach for drug discovery. Drug repurposing infers investigating already approved drugs for new indications, using the available information about pathophysiology of diseases and pharmacodynamics of drugs. In a recent work, more than 3000 FDA approved drugs were tested using virtual screening as potential antiviral agents for COVID-19. In this work, the top ranked five hits from the previous docking results together with drugs of similar chemical feature and/or mechanistic destinations were further tested using AutoDock Vina. The results showed that anti-HCV combinations could be potential therapeutic regimens for COVID-19 infections., Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-021-00691-6., (© Indian Virological Society 2021.)

In this study, a novel and simple fluorescent carbon quantum dots (CQDs) based nano-sensor for colchicine determination has been prepared. The nitrogen doped CQDs probe was prepared using uric acid as a carbon/nitrogen source via a one-step pyrolysis. The sensor is based on inner filter effect (IFE) where colchicine acts as a powerful absorber that affects the excitation of the fluorescer (CQDs). This overlap results in a quantitative attenuation of the fluorescence of CQDs with increasing colchicine concentration in the range of 2-25 μM. The developed sensor has the advantages of simplicity, less time-consuming, convenience and satisfactory selectivity for colchicine determination in pharmaceutical dosage forms.

Hepatitis C is a viral infection that has been declared as a global health problem by the World Health Organization. Egypt has the highest prevalence of hepatitis C virus (HCV) which results in a high morbidity and mortality from chronic liver disease, cirrhosis, and even hepatocellular carcinoma. Cities have lower rates of infection than rural areas. Studies about the abnormally high prevalence of HCV in Egypt ascribed that to the governmental campaign to treat Schistosoma. However, these treatment campaigns have stopped more than 35 years ago, which means that some other modes of transmission must have been involved. The objective of this work is to study the main reasons of HCV prevalence in the Egyptian Delta valley. A questionnaire-based study was conducted by members of the HCV Fighters project. Responses were collected from 949 volunteers (451 HCV patients and 498 healthy volunteers as control). The data were analyzed using SPSS version 19.0. The two-sample proportion test was used for statistical comparison between groups. The most probable risk factors of HCV transmission in Egypt included regular visits to dental clinics (55.2%), previous surgical operations (54.4%), former blood transfusion (52%), intrafamilial HCV infection (45.9%) and history of bilharzial infection (44.3%). Increasing public awareness about modes of transmission and risk factors of HCV infection is a must, especially within family members of HCV patients. Strict commitment to proper medical care precautions by health care practitioners is required., Competing Interests: Competing interestsThe authors declared no competing interests., (© Indian Virological Society 2021.)

A validated method for preconcentration and determination of nateglinide in plasma was developed using vortex-assisted dispersive liquid-liquid microextraction. Different variables that affect extraction efficiency were studied and optimized, including type and volume of extractant, type and volume of disperser, pH of diluent, salt addition effect, centrifugation and vortex time. Nateglinide was extracted using 30 μL of 1-octanol as an extractant and 200 μL of methanol as a disperser. The enrichment factor reached 330 under the optimum conditions. High-performance liquid chromatography/ultraviolet was used for detection using phosphate buffer (pH 2.5, 10 mM): acetonitrile (45:55, v/v) as a mobile phase at a flow rate of 1 mL/min. The method was linear over the range of 50-20,000 ng/mL with a limit of detection of 15 ng/mL (signal-to-noise ratio = 3). Intra- and inter-day precision had %relative standard deviation <6% (n = 3) and the %recoveries were found to be between 102.5 and 105.9%. The proposed method is simple, sensitive, eco-friendly, cost-effective and powerful for microextraction of nateglinide from human plasma samples., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The influence of the addition of various non-ionic surfactants to poly(ethylene glycol) diacrylate-based monolith formulations was studied. Eight non-ionic surfactants having different chemistries were chosen for this study. These surfactants were Brij L4, Span 80, IGEPAL CO-520, Tergitol 15S9, 2,4,7,9-tetramethyl-5-decyne-4,7-diol ethoxylate, Tween 40, Triton X-405, and Tetronic 701. The chemical structures of these surfactants have a variety of functional groups and cover a wide range of molecular weights (360-3600 g/mol), viscosities (60-1500 cP), and hydrophilic-lipophilic balances (1.0-17.6). The formed polymers were characterized by scanning electron microscopy, surface area measurement by the Brunauer-Emmet-Teller method, elemental analysis, and Fourier transform infrared. Four formulations, involving the use of surfactants, resulted in permeable materials when prepared in 150 μm ID silica capillaries. The chromatographic performance of the resulting columns in reversed-phase mode was evaluated and compared using a mixture of alkyl benzenes as test analytes. The highest efficiency and methylene selectivity were observed when Tween 40 was included in the formulation, using decane/decanol/dodecanol as coporogens. This porogenic mixture was successfully used for preparation of monolithic columns from a selection of methacrylate- and styrene-based monomers, including butylmethacrylate, hydroxyethymethacrylate, laurylmethacrylate, glycidyl methacrylate, bisphenol diacrylate, benzylmethacrylate, and N , N -dimethylacrylamide, as well as for divinylbenzene. These results show the applicability of this porogenic mixture for a variety of monolithic formulations, providing an approach for developing a universal porogen system.

Salting-out induced liquid-liquid microextraction method has been developed for plasma sample treatment before determination of alogliptin by high performance liquid chromatography with UV detection. Several parameters were optimized to achieve maximum enrichment, including type of extractant, volume of extractant, type of anion, type of cation, salt amount and pH. The optimum conditions were attained using 500 µL of acetonitrile, added to 1 mL of aqueous sample containing 250 mg of sodium chloride at pH 12. An RP-HPLC method was developed and validated according to the International Conference on Harmonization guidelines M10. The method was linear in the concentration range of 0.1 to 50 µg/mL (correlation coefficient = 0.997). The limit of detection was 0.019 µg/mL and limit of quantitation was 0.06 µg/mL. The method was accurate and precise with an average % recovery of 99.7% and a % relative standard deviation ranging between 1.5 and 2.5. These results showed that the salting-out induced liquid-liquid microextraction methods could be better than other sample preparation protocols in terms of sensitivity, easiness, solvent consumption and waste reduction.

Objective: The Center of Drug Evaluation and Research (CDER) in the food and drug administration (FDA) approves new drugs every year. This review discusses the novel drugs of the FDA in 2018, with emphasis on the breakthrough drugs, the milestones in the approved list, and drugs with the highest expected sales in 2024., Methods: The following scientific search engines were surveyed for the clinical trials of the drugs approved by the FDA in 2018: Pubmed, Springer link, ScienceDirect, Scopus, Wiley online library, Taylor and Francis, and Google Scholar. The total forecast sales were compared based on information from the Cortellis database, EvaluatePharma, and Nature Biobusiness Briefs., Results: The 2018 year was full of good news for the drug market in the USA, with 59 new drug approvals by the FDA, which is the highest number of approvals in the last twenty years. The oncology and the antimicrobial drugs represent almost 50% of the new list, which gives hope to cancer patients and subjects with infectious diseases. In the 2018 FDA list, a number of drugs are expected to exceed 1$ billion dollars of sales by 2024., Conclusion: The new drugs approved by the FDA in 2018 have been reviewed. This year showed the highest number of new drug approvals in the last two decades. Among the 59 drugs approved in 2018, 14 drugs are considered breakthroughs, which revive hope for many poorly managed diseases. The list also contains 19 drugs that are first in class and 43 that were given priority reviews., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)