The Promising Effect of Ascorbic Acid and Paracetamol as Anti-Biofilm and Anti-Virulence Agents against Resistant Escherichia coli.

Escherichia coli is a major cause of serious infections, with antibiotic resistance rendering many treatments ineffective. Hence, novel strategies to combat this pathogen are needed. Anti-virulence therapy is a promising new approach for the subsequent era. Recent research has examined the impact of sub-inhibitory doses of ascorbic acid and paracetamol on Escherichia coli virulence factors. This study evaluated biofilm formation, protease production, motility behavior, serum resistance, expression of virulence-regulating genes (using RT-PCR), and survival rates in a mouse model. Ascorbic acid significantly reduced biofilm formation, protease production, motility, and serum resistance from 100% in untreated isolates to 22-89%, 10-89%, 2-57%, and 31-35% in treated isolates, respectively. Paracetamol also reduced these factors from 100% in untreated isolates to 16-76%, 1-43%, 16-38%, and 31-35%, respectively. Both drugs significantly down-regulated virulence-regulating genes papC, fimH, ompT_m, stcE, fliC, and kpsMTII. Mice treated with these drugs had a 100% survival rate compared with 60% in the positive control group control inoculated with untreated bacteria. This study highlights the potential of ascorbic acid and paracetamol as anti-virulence agents, suggesting their use as adjunct therapies alongside conventional antimicrobials or as alternative treatments for resistant Escherichia coli infections.

Design, Characterization and Biopharmaceutical Applications of Novel Green Boron-Carbon Quantum Dots for Quantification of Apalutamide; Greenness Evaluations.

The diagnosis of prostate cancer has been evolving in the current decade, with expected mortality rates of 499,000 death by the year 2030. Apalutamide (APL) has been approved in 2018 as the first drug for the controlling of prostate cancer. APL significant success warrantied its high global sales, which are expected to surpass 58% of segment market sales (together with another drug; enzalutamide). Therefore, new, fast and environmentally friendly analytical methods are required for its determination for the quality control and biological monitoring purposes. The proposed research designs and evaluates the first fluorimetric approach based on novel porous green boron-doped carbon quantum dots (B@CDs) for the determination of APL in biopharmaceutical matrices. The synthetic approach has high quantum yield (31.15%). B@CDs were characterized using several tools, including transmission electron microscopy (TEM), dynamic light scattering (DLS), FTIR and Energy dispersive X-ray spectroscopy (EDX) which proved their improved surface properties with an average nano-diameter of 3.0 nm. The interaction between B@CDs and APL led to enhancement their fluorescence at 441 nm (excitation at 372 nm). The approach was validated for the determination of APL within concentration range of 15.0-700.0 ng mL- 1 with quantification limit LOQ 4.37 ng mL- 1 and detection limit LOD 1.44 ng mL- 1. The approach was successfully applied for the determination of APL in human plasma and pharmaceutical monitoring of its marketed tablet form. Then, the approach was assessed for its environmental impact using different metrics and proved its ecological greenness.

Synthesis of organic solvent-free nitrogen-doped carbon quantum dots as unique green fluorimetric probes for analysis of abrocitinib in human plasma.

Atopic dermatitis (AD) is a persistent, inflammatory skin condition that impacts approximately 15 to 20% of children and 1 to 3% of adults globally. Common skin manifestations include papules, papulovesicular, and brown or red patches with swelling, crusting, and flaking. Therefore, the drug abrocitinib (ABR) was approved by the US FDA as an oral treatment for atopic dermatitis. The present study outlines the development of innovative, thermostable, and pH-stable organic solvent-free nitrogen-doped carbon dots (N@CQDs) synthesized through a one-step method for evaluating ABR with a notable quantum yield of 33.84% to minimize the use of organic solvents. Their cost-effectiveness, eco-friendly characteristics, and outstanding photocatalytic properties have established them as a promising alternative to conventional luminescent techniques like fluorescent dyes and luminous derivatization technique. The reaction of ABR with N@CQDs led to a significant decrease in the luminescent response of the produced green and stable carbon quantum dots at 513 nm. The detection range was determined to be 1.0-150.0 ng mL-1, with a lower limit of quantitation (LOQ) equal to 0.52 ng mL-1 based on the linear graph. The green method effectively used for analysis of ABR in pharmaceutical tablets and pharmacokinetic study with high sensitivity.

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.

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.

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.

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.

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.

Highly sensitive high-performance thin-layer chromatography method for the simultaneous determination of molnupiravir, favipiravir, and ritonavir in pure forms and pharmaceutical formulations.

Favipiravir, molnupiravir, and ritonavir have been recently approved as the first oral antivirals for treatment of SARS-CoV-2 viral infections. Their combination was reported in several clinical studies, alternatively, to enhance the viral eradication and improve patient's recovery times and rates. Being all orally administered, therefore, the development of new sensitive and validated methodologies for their simultaneous determination is a necessitate. In the proposed research, a sensitive, selective, and simple high-performance thin layer chromatography method was developed and validated for determination of favipiravir, molnupiravir, and ritonavir. Silica gel 60F254 thin layer chromatography plates were used as stationary phase for this separation using mobile phase composed of methylene chloride:ethyl acetate:methanol:25% ammonia (6:3:4:1, v/v/v/v). Densitometric detection was performed at wavelength 289 nm. Peaks of favipiravir, molnupiravir, and ritonavir were resolved at retention factors 0.22, 0.42, and 0.63, respectively. The proposed method was found linear within the specified ranges of 3.75-100.00 µg/mL for molnupiravir and favipiravir, and 2.75-100.00 µg/mL for ritonavir. Limits of detection were found to be 1.12, 1.21, and 0.89 µg/mL for favipiravir, molnupiravir, and ritonavir, respectively. This is the first method to be reported for the simultaneous determination of the cited three antiviral drugs. The method was assessed on novel greenness metrics.

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.

Two Green Micellar HPLC and Mathematically Assisted UV Spectroscopic Methods for the Simultaneous Determination of Molnupiravir and Favipiravir as a Novel Combined COVID-19 Antiviral Regimen.

Following the spread of the COVID-19 pandemic crisis, a race was initiated to find a successful regimen for postinfections. Among those trials, a recent study declared the efficacy of an antiviral combination of favipiravir (FAV) and molnupiravir (MLP). The combined regimen helped in a successful 60% eradication of the SARS-CoV-2 virus from the lungs of studied hamster models. Moreover, it prevented viral transmission to cohosted sentinels. Because both medications are orally bioavailable, the coformulation of FAV and MLP can be predicted. The developed study is aimed at developing new green and simple methods for the simultaneous determination of FAV and MLP and then at their application in the study of their dissolution behavior if coformulated together. A green micellar HPLC method was validated using an RP-C18 core-shell column (5 µm, 150 × 4.6 mm) and an isocratic mixed micellar mobile phase composed of 0.1 M SDS, 0.01 M Brij-35, and 0.02 M monobasic potassium phosphate mixture and adjusted to pH 3.1 at 1.0 mL min-1 flow rate. The analytes were detected at 230 nm. The run time was less than five minutes under the optimized chromatographic conditions. Four other multivariate chemometric model methods were developed and validated, namely, classical least square (CLS), principal component regression (PCR), partial least squares (PLS-1), and genetic algorithm-partial least squares (GA-PLS-1). The developed models succeeded in resolving the great similarity and overlapping in the FAV and MLP UV spectra unlike the traditional univariate methods. All methods were organic solvent-free, did not require extraction or derivatization steps, and were applied for the construction of the simultaneous dissolution profile for FAV tablets and MLP capsules. The methods revealed that the amount of the simultaneously released cited drugs increases up until reaching a plateau after 15 and 20 min for FAV and MLP, respectively. The greenness was assessed on GAPI and found to be in harmony with green analytical chemistry concepts.

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.

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.

Determination of six drugs used for treatment of common cold by micellar liquid chromatography.

The use of organic solvents as eluants in RP-HPLC has an important role to decrease retention time and improve peak shape; however, it has high environmental impacts. Their production and disposal represent economic and biohazard problems. So, alternatives had to be introduced and studied to minimize such pollution. Combination of sodium dodecyl sulfate (SDS) together with polyoxyethylene-23-lauryl ether (Brij-35) was studied as an alternative to the presence of organic solvents on the separation performance of six active pharmaceutical ingredients. Response surface methodology was applied to test the impact of three independent variables; concentrations of SDS and Brij-35, as well as, pH of the mobile phase; on retention, peak symmetry, and resolution of the analytes using a rotatable central composite design. Significant variables were determined and the suggested models for predicting retention and resolution parameters were significant. Meanwhile, the common cold is the most abundant disease treated with over-the-counter (OTC) medications worldwide. In 2015, the USA recorded $9.56 billion total sales of OTC cold and cough medicaments alone, with average individual patient expenditure of $338. The worldwide sales and generics of common cold and cough products keep growing annually. The six active pharmaceutical molecules under study, namely, paracetamol, guaifenesin, pseudoephedrine, ibuprofen, chlorpheniramine, and dextromethorphan, are widely used in common cold products. The predicted optimum conditions were validated using mobile phase consisting of 93.6 mM SDS, 32.0 mM Brij-35, and 10.0 mM sodium dihydrogen phosphate, adjusted at pH 5.2, column temperature 35° C, and detection at 215-nm wavelength. The method was successfully applied to determine 12 different combination formulae of the analytes in their pharmaceutical products and was assessed for greenness on two novel metrics. A thorough comparison to previously reported methods was included and methods were assessed against greenness metrics Green Analytical Procedure Index and Analytical Greenness Metric to demonstrate superiority.

Solvent-free mixed micellar mobile phases: An advanced green chemistry approach for reversed-phase HPLC determination of some antihypertensive drugs.

Minimizing the amount of organic solvents without loss in chromatographic performance has been an important step toward greening analytical methodologies. Mobile-phase composition is the key for maintaining separation efficiency in liquid chromatography while decreasing the procedure hazardousness. If sodium dodecyl sulfate is mixed with Brij-35 in the mobile phase, they could be used as a green alternative for using organic modifiers. In this research, the effect of changing the relative amounts of both surfactants was studied on the chromatographic performance and separation efficiency of ten antihypertensive drugs belonging to different categories. The use of surfactants has many advantages including low cost and toxicity, safe environmental disposal, unique selectivity besides high solubilization capabilities. The optimum separation was maintained using a mobile phase (0.01 M Brij-35, 0.08 M sodium dodecyl sulfate and 0.01 M sodium dihydrogen phosphate/pH 5) on reversed-phase C18 core-shell column at flow rate 1.5 mL/min and temperature 30°C. The method was successfully applied for the determination of the drugs in various marketed dosage forms. International Conference of Harmonization guidelines were followed to validate the developed method. Additionally, the method was verified on the Green Analytical Procedure Index in regards to the greenness and found to be an excellent green alternative method.

Comparison between core-shell and totally porous particle stationary phases for fast and green LC determination of five hepatitis-C antiviral drugs.

The performances of core-shell 2.7 µm and fully porous sub-2 µm particles packed in narrow diameter columns were compared under the same chromatographic conditions. The stationary phases were compared for fast separation and determination of five new antiviral drugs; daclatasvir, sofosbuvir, velpatasvir, simeprevir, and ledipasvir. The gradient elution was done using ethanol as green organic modifier, which is more environmentally friendly. Although both columns provided very good resolution of the five drugs, core-shell particles had proven to be of better efficiency. Under gradient elution conditions, core-shell particles exhibited faster elution, better peak shape, and enhanced resolution adding to lower system backpressure. The column backpressure on sub-2 µm particles was more than twice that on core-shell particles. This gives a chance to use conventional high-performance liquid chromatography conditions without needing special instrumentation as that required for ultra-high performance liquid chromatography. The method was validated for determination of the five drugs by gradient elution using mobile phase composed of organic modifier ethanol and aqueous part containing 0.75 g sodium octane sufonate and 3.0 g sodium dihydrogen phosphate per liter at pH of 6.15. Detection was done using UV-detector set at 210 nm. The linearity, accuracy, and precision were found very good within the concentration range of 2-200 µg/mL.

Chromatographic analysis of some drugs employed in erectile dysfunction therapy: qualitative and quantitative studies using calixarene stationary phase.

In this study, the effect of change in chromatographic process variables on the retention behavior of four drugs employed in erectile dysfunction therapy on a calixarene stationary phase is described. Three of these drugs are known to treat erectile dysfunction, namely, sildenafil citrate, tadalafil, and apomorphine hydrochloride, and one drug that is used as opioid analgesic, tramadol hydrochloride, which is quiet widely misused to treat premature ejaculation. The results indicate the importance of considering the structure and pKa values of drugs to be separated along with mobile phase composition. A new optimized, rapid, and accurate liquid chromatography method is also established for simultaneous determination of sildenafil citrate, tadalafil, and apomorphine hydrochloride in pharmaceutical preparations and bulk powders. The chromatographic separation of the three pharmaceuticals was achieved on a calixarene column in less than 10 min using a binary mobile phase of 35% acetonitrile and 65% 50 mM sodium perchlorate pH2.5 at 1 mL/min flow rate. The method was validated for system efficiency, linearity, accuracy, precision, limits of detection and quantitation, specificity, stability, and robustness. Statistical analysis proved that the method enabled reproducible and selective quantification of all three analytes in bulk drugs and in pharmaceutical preparations.

Tracking the Variations in Trace and Heavy Elements in Smoking Products Marketed in Oman and Egypt: Risk Assessment After Implementation of Constraining Protocols.

Tobacco smoking is becoming one of the major worldwide concerns regarding environmental pollution as well as health threats. In 2005, the World Health Organization (WHO) released the Framework Convention On Tobacco Control (FCTC), which outlined protocols for controlling tobacco products. Oman was one of the leading countries to follow these protocols; however, Egypt has only followed these protocols recently in 2020. One of the main challenges in tobacco product control is the variation in their trace element's types and amounts from country to country owing to differences in agriculture techniques and used chemical additives. Smoking releases different toxic metal ions found in them into the air, and hence, analyzing trace amounts of metals in tobacco smoking products is becoming more critical. The proposed research aims to evaluate the current levels of 11 heavy metals (namely, As, Pb, Cd, Co, Cr, Be, Ba, Mn, Ni, Fe, and Hg) in 22 tobacco products available in Egypt and Oman using inductively coupled plasma optical emission spectroscopy and a direct mercury analyzer. Although some elements such as Be, Co, and Cd were absent, the positive detection of As and Pb and the levels of Ba, Cr, and Ni are still alarming, especially for heavy smokers. The obtained results were then statistically related to previously published data in 2017 to explore the effectiveness of implementing the FCTC protocols within the Egyptian market. The outcomes suggested a positive impact of FCTC protocol implementation in Egypt, besides the lower levels of elemental content for Omani products compared to the Egyptian market.

Design, Characterization, and Bioanalytical Applications of Green Terbium- and Nitrogen-Doped Carbon Quantum Dots as a Fluorescent Nanoprobe for Omadacycline Analysis.

Terbium- and nitrogen-doped carbon quantum dots (Tb,N@CQDs) were greenly created employing microwave synthesis from plum juice with terbium nitrate. The synthesis of Tb,N@CQDs was fast (7 min) with a high quantum yield (35.44%). Tb,N@CQDs were fully characterized using transmission electron microscopy, Zeta potential analysis, fluorescence, and ultraviolet spectroscopy. Omadacycline (OMC) is a broad-spectrum tetracycline that has been recently approved by the United States Food and Drug Act (FDA) in October 2018. OMC is the first oral aminomethylcycline class antibiotic drug that was authorized for the treatment of acute skin structure infections and community-acquired pneumonia. Tb,N@CQDs exhibited emission at 440 nm after excitation at 360 nm, where their fluorescence intensity showed a reduction upon addition of OMC. The experimental parameters were further studied and optimized. The linear range was between 40 and 60 parts per billion (ppb), with (limit of quantitation) equal to 34.78 ppb. The proposed approach was validated for bioanalytical purposes using FDA guidelines and proved to be straightforward, cheap, highly sensitive, and very selective, which can be used in clinical studies. The developed approach proved to be green using some current assessment metrics and was applied successfully for the determination of OMC in human plasma, milk, and pharmaceutical formulations as well as pharmacokinetic study.