Verapamil-Loaded Cubosomes for Enhancing Intranasal Drug Delivery: Development, Characterization, Ex Vivo Permeation, and Brain Biodistribution Studies.

Verapamil hydrochloride (VRP), an antihypertensive calcium channel blocker drug has limited bioavailability and short half-life when taken orally. The present study was aimed at developing cubosomes containing VRP for enhancing its bioavailability and targeting to brain for cluster headache (CH) treatment as an off-label use. Factorial design was conducted to analyze the impact of different components on entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and percent drug release. Various in-vitro characterizations were performed followed by pharmacokinetic and brain targeting studies. The results revealed the significant impact of glyceryl monooleate (GMO) on increasing EE%, PS, and ZP of cubosomes with a negative influence on VRP release. The remarkable effect of Poloxamer 407 (P407) on decreasing EE%, PS, and ZP of cubosomes was observed besides its influence on accelerating VRP release%. The DSC thermograms indicated the successful entrapment of the amorphous state of VRP inside the cubosomes. The design suggested an optimized formulation containing GMO (50% w/w) and P407 (5.5% w/w). Such formulation showed a significant increase in drug permeation through nasal mucosa with high Er value (2.26) when compared to VRP solution. Also, the histopathological study revealed the safety of the utilized components used in the cubosomes preparation. There was a significant enhancement in the VRP bioavailability when loaded in cubosomes owing to its sustained release favored by its direct transport to brain. The I.N optimized formulation had greater BTE% and DTP% at 183.53% and 90.19%, respectively in comparison of 41.80% and 59% for the I.N VRP solution.

Greener and Whiter Analytical Chemistry Using Cyrene as a More Sustainable and Eco-Friendlier Mobile Phase Constituent in Chromatography.

Cyrene (dihydrolevoglucosenone) was evaluated for the first time as a potential sustainable mobile phase solvent in reversed-phase chromatography. As a benign biodegradable solvent, Cyrene is an attractive replacement to classical non-green organic chromatographic solvents such as acetonitrile and a modifier, co-eluent to known green solvents such as ethanol. Compared to ethanol, Cyrene is less toxic, non-flammable, biobased, biodegradable, and a cheaper solvent. A fire safety spider chart was generated to compare the properties of Cyrene to ethanol and show its superiority as a greener solvent. Cyrene's behavior, advantages, and drawbacks in reversed-phase chromatography, including the cut-off value of 350 nm, elution power, selectivity, and effect on the column, were investigated using a model drug mixture of moxifloxacin and metronidazole. A monolithic C18 (100 × 4.6 mm) column was used as a stationary phase. Different ratios of Cyrene: ethanol with an aqueous portion of sodium acetate buffer mobile phases were tested. A mobile phase consisting of Cyrene: ethanol: 0.1 M sodium acetate buffer pH 4.25 (8:13:79, v/v/v) was selected as the most suitable mobile phase system for separating and simultaneously determining metronidazole and moxifloxacin. The greenness and whiteness of the method were evaluated using the qualitative green assessment tool AGREE and the white analytical chemistry assessment tool RGB12. Further potentials of Cyrene as a solvent or modifier in normal phase chromatography, liquid chromatography-mass spectrometry, and supercritical fluid chromatography are discussed.

Development of cysteine-doped MnO2 quantum dots for spectrofluorimetric estimation of copper: applications in different matrices.

Copper (Cu) plays a role in maintaining healthy nerve cells and the immune system. Osteoporosis is a high-risk factor for Cu deficiency. In the proposed research, unique green, fluorescent cysteine-doped MnO2 quantum dots (Cys@MnO2 QDs) were synthesized and assessed for the determination of Cu in different food and hair samples. The developed quantum dots were synthesized with the help of cysteine using a straightforward ultrasonic approach to create 3D fluorescent Cys@MnO2 QDs. The resulting QDs' morphological and optical characteristics were carefully characterized. By adding Cu ions, the intensity of fluorescence for the produced Cys@MnO2 QDs was found to be dramatically reduced. Additionally, the applicability of Cys@MnO2 QDs as a new luminous nanoprobe was found to be strengthened by the quenching effect grounded on the Cu-S bonding. The concentrations of Cu2+ ions were estimated within the range of 0.06 to 7.00 µg mL-1, with limit of quantitation equal to 33.33 ng mL-1 and detection limit equal to 10.97 ng mL-1. The Cys@MnO2 QD technique was applied successfully for the quantification of Cu in a variety of foods, including chicken meat, turkey, and tinned fish, as well as in human hair samples. The chance that this novel technique could be a useful tool for figuring out the amount of cysteine in bio-samples is increased by the sensing system's remarkable advantages, which include being rapid, simple, and economical.

Fast and Sensitive Bioanalytical Method for the Determination of Deucravacitinib in Human Plasma Using HPLC-MS/MS: Application and Greenness Evaluation.

Plaque psoriasis is a common, long-lasting illness that affects the immune system and causes significant negative impacts on a patient's physical health, well-being, and ability to work effectively. Deucravacitinib (DEU) is the first oral medication used in the treatment of plaque psoriasis, a chronic skin condition that causes red, scaly patches on the skin. DEU is a type of medication called an oral Janus kinase (JAK) inhibitor, which works by blocking specific enzymes that play a role in the inflammation and immune response associated with psoriasis. Therefore, a quick, easy, novel, reliable, sensitive, and straightforward liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used to analyze DEU in plasma samples. The LC-MS/MS method for the determination of DEU in human plasma was based on using trimethoprim as an internal standard (IS). The separation of DEU and IS was carried out via liquid-liquid extraction (LLE). The extract was then subjected to the chromatographic system separation using the ACE-C18 column (4.6 × 100 mm, 5 µm). The mobile phase employed consisted of methanol and a solution of 2 mM ammonium formate (80:20 v/v, respectively). The flow rate used was set at 0.9 mL min-1. The creative strategy was performed by running an ABSCIEX API 4000 mass spectrometer with an electron spray ionization source in multiple reaction monitoring (MRM) mode. The ion transitions m/z 426.3 → 358.2 were used for DEU quantitation, while the ion transitions m/z 291.1 → 261.1 were used for trimethoprim quantitation. The accuracy, precision, linearity, recovery, and selectivity of DEU were deemed acceptable when validated for a concentration range between 0.500 and 601.050 ng/mL, utilizing a weighting factor of 1/x2.

Recent advances in chiral selectors immobilization and chiral mobile phase additives in liquid chromatographic enantio-separations: A review.

For decades now, the separation of chiral enantiomers of drugs has been gaining the interest and attention of researchers. In 1991, the first guidelines for development of chiral drugs were firstly released by the US-FDA. Since then, the development in chromatographic enantioseparation tools has been fast and variable, aiming at creating a suitable environment where the physically and chemically identical enantiomers can be separated. Among those tools, the immobilization of chiral selectors (CS) on different stationary phases and the chiral mobile phase additives (CMPA) which have been progressed and studied extensively. This review article highlights the major advances in immobilization of CS together with their different recognition mechanisms as well as CMPA as a cheaper and successful alternative for chiral stationary phases. Moreover, the role of molecular modeling tool as a pre-step in the choice of CS for evaluating possible interactions with different ligands has been pointed up. Illustrations of reported methods and updates for immobilized CS and CMPA have been included.

Zinc(II) complexation strategy for ultra-sensitive fluorimetric estimation of molnupiravir: Applications and greenness evaluation.

The endemicity of the pandemic coronavirus disease 2019 (COVID-19) infection proved to be transitional only. Spikes are forming again in 2023, and high expectations are returning for reinfections and viral mutations. Molnupiravir (MOL) has been approved as an oral antiviral drug for the treatment of the COVID-19 causative virion. Therefore, the development of an ultrasensitive, instantaneous, and cost-effective method for the quantification of MOL in real plasma samples and formulated dosage form are mandatory. The proposed approach is based on the synthesis of a MOL metal-chelation product. MOL as a ligand was chelated with 1.0 mM zinc(II) in an acetate buffer (pH 5.3). After illumination at 340 nm, the intensity of the MOL fluorescence measured at 386 nm was increased by about 10-fold. The linearity range was found to be from 60.0 to 800.0 ng mL-1 with limit of quantitation (LOQ) of 28.6 ng mL-1 . Two methods were utilized for measuring the greenness of the proposed method (Green Analytical Procedure Index [GAPI] and analytical greenness metric [AGREE] methods), with results equal to 0.8. The binding stoichiometry of MOL with the zinc(II) ion was found to be 2:1. All the experimental parameters were optimized and validated using International Conference on Harmonization (ICH) and United States Food and Drug Administration (US-FDA) recommendations. Furthermore, the fluorescent probes were successfully utilized in real human plasma with high percentages of recovery (95.6%-97.1%) without any matrix interferences. The mechanism of fluorescent complex formation was confirmed using 1 H NMR in the presence and absence of Zn(II). The method was further utilized for testing content uniformity of MOL in its marketed capsule dosage forms.

LC-MS/MS bioanalytical method for the quantitative analysis of nifedipine, bisoprolol, and captopril in human plasma: Application to pharmacokinetic studies.

In this study, the development and validation of an accurate and highly sensitive LC-MS/MS method were performed for the estimation of nifedipine, bisoprolol and captopril in real human plasma. Liquid-liquid extraction using tert-butyl methyl ether was efficiently applied for extraction of the analytes from plasma samples. The chromatographic separation was carried out using an isocratic elution mode on the X-terra MS C18 column (4.6 × 50 mm, 3.5 µm). The mobile phase consisted of methanol-0.1% formic acid (95:5, v/v) for determination of nifedipine and bisoprolol and acetonitrile-0.1% formic acid (70:30, v/v) for determination of captopril with a flow rate of 0.5 ml/min. Acceptable results regarding the different validation characteristics of the analytes were obtained in accordance with US Food and Drug Administration recommendations for bioanalytical methods. The developed approach was linear over concentration ranges of 0.5-130.0, 50.0-4,500.0 and 0.3-30.0 ng/ml for nifedipine, captopril and bisoprolol, respectively. The method revealed a sufficient lower limit of quantification in the range of 0.3-50.0 ng/ml, as well as high recovery percentages, indicating high bioanalytical applicability. The proposed method was efficiently applied to a pharmacokinetic evaluation of a fixed-dose combination of the analytes in healthy male volunteers.

Studying molecular interactions via capillary electrophoresis and microscale thermophoresis: A review.

The process of choosing the most proper technique for studying the molecular interactions is based on critical factors such as instrumentation complexity, automation, experimental procedures, analysis time, consumables, and cost-value. This review has tracked the use of affinity capillary electrophoresis (ACE) and microscale thermophoresis (MST) techniques in the evaluation of molecular binding among different molecules during the 5 years 2016-2021. ACE has proved to be an attractive technique for biomolecular characterization with high resolution efficiency where small variations in several controlling factors can much improve such efficiency compared to other analytical techniques. Meanwhile, MST has proved its higher sensitivity for smaller amounts of complex non-purified biosamples without affecting its robustness while providing high through output. However, the main motivation to review both techniques in the proposed review was their capability to carry out all experiments without the need for immobilizing one interacting partner, besides a great flexibility in the use of buffering systems. The proposed review demonstrates the importance of both techniques in different areas of life sciences. Moreover, the recent advances in exploiting ACE and MST in other research interests have been discussed.

Green Chemometric Determination of Cefotaxime Sodium in the Presence of Its Degradation Impurities Using Different Multivariate Data Processing Tools; GAPI and AGREE Greenness Evaluation.

Four eco-friendly, cost-effective, and fast stability-indicating UV-VIS spectrophotometric methods were validated for cefotaxime sodium (CFX) determination either in the presence of its acidic or alkaline degradation products. The applied methods used multivariate chemometry, namely, classical least square (CLS), principal component regression (PCR), partial least square (PLS), and genetic algorithm-partial least square (GA-PLS), to resolve the analytes' spectral overlap. The spectral zone for the studied mixtures was within the range from 220 to 320 nm at a 1 nm interval. The selected region showed severe overlap in the UV spectra of cefotaxime sodium and its acidic or alkaline degradation products. Seventeen mixtures were used for the models' construction, and eight were used as an external validation set. For the PLS and GA-PLS models, a number of latent factors were determined as a pre-step before the models' construction and found to be three for the (CFX/acidic degradants) mixture and two for the (CFX/alkaline degradants) mixture. For GA-PLS, spectral points were minimized to around 45% of the PLS models. The root mean square errors of prediction were found to be (0.19, 0.29, 0.47, and 0.20) for the (CFX/acidic degradants) mixture and (0.21, 0.21, 0.21, and 0.22) for the (CFX/alkaline degradants) mixture for CLS, PCR, PLS, and GA-PLS, respectively, indicating the excellent accuracy and precision of the developed models. The linear concentration range was studied within 12-20 µg mL-1 for CFX in both mixtures. The validity of the developed models was also judged using other different calculated tools such as root mean square error of cross validation, percentage recoveries, standard deviations, and correlation coefficients, which indicated excellent results. The developed methods were also applied to the determination of cefotaxime sodium in marketed vials, with satisfactory results. The results were statistically compared to the reported method, revealing no significant differences. Furthermore, the greenness profiles of the proposed methods were assessed using the GAPI and AGREE metrics.

Toxic Elemental Impurities in Herbal Weight Loss Supplements; A Study Using ICP-OES Microwave-Assisted Digestion.

The tendency of using weight loss herbal preparations is continuously increasing, especially for the widespread consumption of junk food that is characterized by high calories. Weight loss herbal preparations are considered a type of food supplement product, and, as such, the regulations governing their quality control might be minimal. These products could be locally formulated in any country or internationally imported. Being non-controlled products, the herbal weight-loss products may contain high levels of elemental impurities that might exceed the permissible ranges. Moreover, these products contribute to the total daily intake (TDI) of such elements, which might represent concerns about their potential toxicological danger. In this research, the elemental contents in such products were investigated. The inductively coupled plasma with optical emission spectrometer (ICP-OES) was used to determine the levels of 15 elemental contents, namely, Na, K, Ca, Mg, Al, Cu, Fe, Li, Mn, As, Co, Cr, Cd, Ni and Pb. The results showed that seven micro-elements, namely Cd, Co, Ni, Cr, Pb, Li and Cu, were either not detectable or at a concentration much lower than their tolerable limits. However, all studied macro-elements (Na, K, Ca and Mg), together with Fe, were found at considerable, yet safe levels. On the other hand, Mn, Al and As contents showed perturbing levels in some of the studied products. Finally, a conclusion was highlighted for the necessity for stricter surveillance of such herbal products.

An Innovative Polymer-Based Electrochemical Sensor Encrusted with Tb Nanoparticles for the Detection of Favipiravir: A Potential Antiviral Drug for the Treatment of COVID-19.

An innovative polymer-based electro-sensor decorated with Tb nanoparticles has been developed for the first time. The fabricated sensor was utilized for trace determination of favipiravir (FAV), a recently US FDA-approved antiviral drug for the treatment of COVID-19. Different techniques, including ultraviolet-visible spectrophotometry (UV-VIS), cyclic voltammetry (CV), scanning electron microscope (SEM), X-ray Diffraction (XRD) and electrochemical impedance spectroscopy (EIS), were applied for the characterization of the developed electrode TbNPs@ poly m-THB/PGE. Various experimental variables, including pH, potential range, polymer concentration, number of cycles, scan rate and deposition time, were optimized. Moreover, different voltammetric parameters were examined and optimized. The presented SWV method showed linearity over the range of 10-150 × 10-9 M with a good correlation coefficient (R = 0.9994), and the detection limit (LOD) reached 3.1 × 10-9 M. The proposed method was applied for the quantification of FAV in tablet dosage forms and in human plasma without any interference from complex matrices, obtaining good % recovery results (98.58-101.93%).

Comparative Evaluation of Reversed Stationary Phase Geometries and Greener Systems on HPLC and UHPLC Using Five Recent Hepatitis-C Antivirals.

BACKGROUND: Being the most widely used LC mode, reversed-phase (RP)-HPLC accounts for the highest percentage of HPLC separations. The main aim of the green analytical chromatographer is to enhance the efficiency of separations in short analysis times, using the ecologically safest materials and lowest energy consumption. OBJECTIVE: Being the heart of any chromatography where the actual separations take place, LC columns have diverse varieties which include different stationary phase geometries as well as different particles sizes. The rationale for column choice is quite complicated. Totally porous, core-shell particles, and monolithic rods are stationary phase types manufactured in RP-mode. The main objective of this research study is to aid in the selection of HPLC or ultra-high performance lquid chromatography (UHPLC) instrumentation. METHODS: In this research article, three different column packing phases were evaluated and compared by both HPLC and UHPLC techniques. The purpose was to explore the best rational choice of column packing as well as LC instrumentation, when using greener chromatographic conditions. RESULTS: The study showed core-shell particles were superior in both HPLC and UHPLC techniques. CONCLUSION: Core-shell particles enabled the utilization of greener mobile phase compositions. Monolithic columns showed better tolerance of greener mobile phase flow rates, without considerable loss of performance. HIGHLIGHTS: The use of greener organic solvents was assessed on different stationary phase geometries. The separation efficiency for five recent antiviral drugs was evaluated, in order to give better understanding of the way for column choice according to the underlying experimental conditions. UHPLC and HPLC were compared comprehensively for applicability and cost-effectiveness.

Dinebra retroflexa Herbal Phytotherapy: A Simulation Study Based on Bleomycin-Induced Pulmonary Fibrosis Retraction Potential in Swiss Albino Rats.

Background and Objectives: Fibrotic lung disease is one of the main complications of many medical conditions. Therefore, the use of anti-fibrotic agents may provide a chance to prevent, or at least modify, such complication. The aim of this study was to evaluate the protective pulmonary anti-fibrotic and anti-inflammatory effects of Dinebra retroflexa. Materials and methods: Dinebra retroflexa methanolic extract and its synthesized silver nanoparticles were tested on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/5 mL/kg-Saline) as a supposed model for induced lung fibrosis. The weed evaluation was performed by intratracheal instillation of Dinebra retroflexa methanolic extract and its silver nanoparticles (35 mg/100 mL/kg-DMSO, single dose). Results: The results showed that both Dinebra retroflexa methanolic extract and its silver nanoparticles had a significant pulmonary fibrosis retraction potential, with Ashcroft scores of three and one, respectively, and degrees of collagen deposition reduction of 33.8 and 46.1%, respectively. High-resolution UHPLC/Q-TOF-MS/MS metabolic profiling and colorimetrically polyphenolic quantification were performed for further confirmation and explanation of the represented effects. Such activity was believed to be due to the tentative identification of twenty-seven flavonoids and one phenolic acid along with a phenolic content of 57.8 mg/gm (gallic acid equivalent) and flavonoid content of 22.5 mg/gm (quercetin equivalent). Conclusion: Dinebra retroflexa may be considered as a promising anti-fibrotic agent for people at high risk of complicated lung fibrosis. The results proved that further clinical trials would be recommended to confirm the proposed findings.

Antitrypanosomal, Antitopoisomerase-I, and Cytotoxic Biological Evaluation of Some African Plants Belonging to Crassulaceae; Chemical Profiling of Extract Using UHPLC/QTOF-MS/MS.

In our continuous study for some African plants as a source for antitrypanosomally and cytotoxic active drugs, nine different plants belonging to the Crassulaceae family have been selected for the present study. Sedum sieboldii leaves extract showed an antitrypanosomal activity against Trypanosoma brucei with an IC50 value of 8.5 µg/mL. In addition, they have cytotoxic activities against (HCT-116), (HEPG-2) and (MCF-7), with IC50 values of 28.18 ± 0.24, 22.05 ± 0.66, and 26.47 ± 0.85 µg/mL, respectively. Furthermore, the extract displayed inhibition against Topoisomerase-1 with an IC50 value of 1.31 µg/mL. It showed the highest phenolics and flavonoids content among the other plants' extracts. In order to identify the secondary metabolites which may be responsible for such activities, profiling of the polar secondary metabolites of S. sieboldii extract via Ultra-Performance Liquid Chromatography coupled to High-Resolution QTOF-MS operated in negative and positive ionization modes, which revealed the presence of 46 metabolites, including flavonoids, phenolic acids, anthocyanidins, coumarin, and other metabolites.

UHPLC Enantiomer Resolution for the ɑ/ß-Adrenoceptor Antagonist R/S-Carvedilol and Its Major Active Metabolites on Chiralpak IB N-5.

Carvedilol (CAR), a racemic lipophilic aryloxy propanolamine, acts as a selective α1-adrenoreceptor antagonist and a nonselective ß-adrenoreceptor antagonist. CAR metabolism mainly produces three active metabolites: desmethyl carvedilol (DMC), 4'-hydroxy carvedilol (4'OHC) and 5'-hydroxy carvedilol (5'OHC). The oxidative S-(-)-metabolites contribute to the ß-antagonistic effect, yet not to the α-antagonistic effect to be observed after drug dosage. Therefore, the three ß-adrenoceptor blocking metabolites, which are structurally closely related to the parent CAR, are included into the development of a bioanalytical quantitative method for all major active species relevant with respect to adrenoceptor-blockade. Because of the given pharmacological profile, resolution of the enantiomers of carvedilol, of 4'- and 5'-hydroxy carvedilol as well as of DMC, is mandatory. The current study aims to determine the response surface for the enantiomer separation of the parent CAR as well as the major metabolites on a suitable chiral stationary phase. Design of experiment approach (DoE) was utilized in an initial screening phase followed by central-composite design for delimitation of the response surface for resolution of the four enantiomeric pairs in least run time. The impact of chromatographic variables (composition and percentage of organic modifier(s), buffer type, buffer pH, flow rate) on critical peaks resolution and adjusted retention time was evaluated, in order to select the most significant critical quality attributes. On this basis, a robust UHPLC-UV method was developed and optimized for the simultaneous, enantioselective determination of CAR along with its major active metabolites (4'OHC, 5'OHC, and DMC) on Chiralpak IBN-5. The optimized UHPLC-UV method (which includes metoprolol as the internal standard) was validated according to the ICH M10 guidelines for bioanalytical methods and proven to be linear, precise, accurate, and robust. The validated assay was applied to plasma samples from cardiovascular patients treated with rac-CAR (blood randomly drawn at different times after oral CAR intake). In order to provide more insight into the mechanism of the enantiomer separation of CAR and its metabolites on the CSP, docking experiments were performed. Molecular simulation studies suggest the chiral recognition to be mainly due to different binding poses of enantiomers of the same compound.

Microscale Thermophoresis and Molecular Modelling to Explore the Chelating Drug Transportation in the Milk to Infant.

The microscale thermophoresis (MST) technique was utilized to investigate lactoferrin-drug interaction with the iron chelator, deferiprone, using label-free system. MST depends on the intrinsic fluorescence of one interacting partner. The results indicated a significant interaction between lactoferrin and deferiprone. The estimated binding constant for the lactoferrin-deferiprone interaction was 8.9 × 10-6 ± 1.6, SD, which is to be reported for the first time. Such significant binding between lactoferrin and deferiprone may indicate the potentiation of the drug secretion into a lactating mother's milk. The technique showed a fast and simple approach to study protein-drug interaction while avoiding complicated labeling procedures. Moreover, the binding behavior of deferiprone within the binding sites of lactoferrin was investigated through molecular docking which reflected that deferiprone mediates strong hydrogen bonding with ARG121 and ASP297 in pocket 1 and forms H-bond and ionic interaction with ASN640 and ASP395, respectively, in pocket 2 of lactoferrin. Meanwhile, iron ions provide ionic interaction with deferiprone in both of the pockets. The molecular dynamic simulation further confirmed that the binding of deferiprone with lactoferrin brings conformational changes in lactoferrin that is more energetically stable. It also confirmed that deferiprone causes positive correlation motion in the interacting residues of both pockets, with strong negative correlation motion in the loop regions, and thus changes the dynamics of lactoferrin. The MM-GBSA based binding free energy calculation revealed that deferiprone exhibits ∆G TOTAL of -63,163 kcal/mol in pocket 1 and -63,073 kcal/mol in pocket 2 with complex receptor-ligand difference in pocket 1 and pocket 2 of -117.38 kcal/mol and -111.54 kcal/mol, respectively, which in turn suggests that deferiprone binds more strongly in the pocket 1. The free energy landscape of the lactoferrin-deferiprone complex also showed that this complex remains in a high energy state that confirms the strong binding of deferiprone with the lactoferrin. The current research concluded that iron-chelating drugs (deferiprone) can be transported from the mother to the infant in the milk because of the strong attachment with the lactoferrin active pockets.

Microscale thermophoresis as a powerful growing analytical technique for the investigation of biomolecular interaction and the determination of binding parameters.

Thein vitropanel of technologies to address biomolecular interactions are in play, however microscale thermophoresis is continuously increasing in use to represent a key player in this arena. This review highlights the usefulness of microscale thermophoresis in the determination of molecular and biomolecular affinity interactions. This work reviews the literature from January 2016 to January 2022 about microscale thermophoresis. It gives a summarized overview about both the state-of the art and the development in the field of microscale thermophoresis. The principle of microscale thermophoresis is also described supported with self-created illustrations. Moreover, some recent advances are mentioned that showing application of the technique in investigating biomolecular interactions in different fields. Finally, advantages as well as drawbacks of the technique in comparison with other competing techniques are summarized.

Fabrication of novel quantum dots for the estimation of COVID-19 antiviral drug using green chemistry: application to real human plasma.

The COVID-19 pandemic has encouraged the search for novel antiviral medications. Recently, molnupiravir (MOL) has been approved as an oral antiviral to manage COVID-19. Thus, the development of sensitive and cost-effective methods for quantification of MOL in real plasma samples (pharmacokinetic) and pharmaceutical tablets is required. Herein, we present the fabrication of novel fluorescent polyamine quantum dots (PA@CQDs) fabricated from apricots using one step synthesis for analysis of MOL. The relative fluorescence intensity (RFI) of the synthesized quantum dots was influentially quenched by the addition of molnupiraivr. The linear range was found to be between 2-70 ng mL-1 with lower limit of quantitation (LOQ) equal to 1.61 ng mL-1. The fluorescent probe was successfully utilized in a pharmacokinetic study of MOL with maximum plasma concentration (C max) 920.2 ± 6.12 ng mL-1 without any matrix interference. The sensitivity and selectivity of the presented method allow its application in clinical laboratories.

Analytical Performance and Greenness Evaluation of Five Multi-Level Design Models Utilized for Impurity Profiling of Favipiravir, a Promising COVID-19 Antiviral Drug.

In 2018, the discovery of carcinogenic nitrosamine process related impurities (PRIs) in a group of widely used drugs led to the recall and complete withdrawal of several medications that were consumed for a long time, unaware of the presence of these genotoxic PRIs. Since then, PRIs that arise during the manufacturing process of the active pharmaceutical ingredients (APIs), together with their degradation impurities, have gained the attention of analytical chemistry researchers. In 2020, favipiravir (FVR) was found to have an effective antiviral activity against the SARS-COVID-19 virus. Therefore, it was included in the COVID-19 treatment protocols and was consequently globally manufactured at large-scales during the pandemic. There is information indigence about FVR impurity profiling, and until now, no method has been reported for the simultaneous determination of FVR together with its PRIs. In this study, five advanced multi-level design models were developed and validated for the simultaneous determination of FVR and two PRIs, namely; (6-chloro-3-hydroxypyrazine-2-carboxamide) and (3,6-dichloro-pyrazine-2-carbonitrile). The five developed models were classical least square (CLS), principal component regression (PCR), partial least squares (PLS), genetic algorithm-partial least squares (GA-PLS), and artificial neural networks (ANN). Five concentration levels of each compound, chosen according to the linearity range of the target analytes, were used to construct a five-level, three-factor chemometric design, giving rise to twenty-five mixtures. The models resolved the strong spectral overlap in the UV-spectra of the FVR and its PRIs. The PCR and PLS models exhibited the best performances, while PLS proved the highest sensitivity relative to the other models.

Recent Advances in Electrochemical Sensing of Hydrogen Peroxide (H2O2) Released from Cancer Cells.

Cancer is by far the most common cause of death worldwide. There are more than 200 types of cancer known hitherto depending upon the origin and type. Early diagnosis of cancer provides better disease prognosis and the best chance for a cure. This fact prompts world-leading scientists and clinicians to develop techniques for the early detection of cancer. Thus, less morbidity and lower mortality rates are envisioned. The latest advancements in the diagnosis of cancer utilizing nanotechnology have manifested encouraging results. Cancerous cells are well known for their substantial amounts of hydrogen peroxide (H2O2). The common methods for the detection of H2O2 include colorimetry, titration, chromatography, spectrophotometry, fluorimetry, and chemiluminescence. These methods commonly lack selectivity, sensitivity, and reproducibility and have prolonged analytical time. New biosensors are reported to circumvent these obstacles. The production of detectable amounts of H2O2 by cancerous cells has promoted the use of bio- and electrochemical sensors because of their high sensitivity, selectivity, robustness, and miniaturized point-of-care cancer diagnostics. Thus, this review will emphasize the principles, analytical parameters, advantages, and disadvantages of the latest electrochemical biosensors in the detection of H2O2. It will provide a summary of the latest technological advancements of biosensors based on potentiometric, impedimetric, amperometric, and voltammetric H2O2 detection. Moreover, it will critically describe the classification of biosensors based on the material, nature, conjugation, and carbon-nanocomposite electrodes for rapid and effective detection of H2O2, which can be useful in the early detection of cancerous cells.