Development of an eco-friendly fluorescent probe for mefenamic acid sensing in pharmaceuticals and biofluids.

Mefenamic acid, renowned for its analgesic properties, stands as a reliable choice for alleviating mild to moderate pain. However, its versatility extends beyond pain relief, with ongoing research unveiling its promising therapeutic potential across diverse domains. A straightforward, environmentally friendly, and sensitive spectrofluorometric technique has been developed for the precise quantification of the analgesic medication, mefenamic acid. This method relies on the immediate reduction of fluorescence emitted by a probe upon interaction with varying concentrations of the drug. The fluorescent probe utilized, N-phenyl-1-naphthylamine (NPNA), was synthesized in a single step, and the fluorescence intensities were measured at 480 nm using synchronous fluorescence spectroscopy with a wavelength difference of 200 nm. Temperature variations and lifetime studies indicated that the quenching process was static. The calibration curve exhibited linearity within the concentration range of 0.50-9.00 µg/mL, with a detection limit of 60.00 ng/mL. Various experimental parameters affecting the quenching process were meticulously examined and optimized. The proposed technique was successfully applied to determine mefenamic acid in pharmaceutical formulations, plasma, and urine, yielding excellent recoveries ranging from 98% to 100.5%. The greenness of the developed method was evaluated using three metrics: the Analytical Eco-scale, AGREE, and the Green Analytical Procedure Index.

Different spectrophotometric methods for simultaneous quantitation of Vericiguat and its alkaline degradation product: a comparative study with greenness profile assessment.

Investigations concerning novel drugs and their induced degradation products are necessary for clinical research and quality control in the pharmaceutical industry. Four spectrophotometric techniques have been performed for simultaneous quantitation of Vericiguat (VER) and its alkali-induced degradation product (ADP) without prior separation. Method A is a dual wavelength method (DW) that estimates the absorbance difference at 314-328 nm, and 246-262 nm for VER and ADP; respectively. Method B uses a ratio difference method (RD) to estimate the ratio spectrum's amplitude difference (DP318-342) and (DP284-292) for VER and ADP; respectively. Method C uses a first derivative ratio method (1DD) to estimate the peak ratio spectrum amplitude of the first derivative at 318 and 275 nm for VER and ADP; respectively. Method D uses the mean centering of the ratio spectra (MCR) to estimate amplitude values for VER and ADP at 337 and 292 nm; respectively. In a concentration range of 5.00-50.00 µg/mL for VER and 5.00-100.00 µg/mL for ADP, the methods were validated following ICH criteria and utilized to estimate VER in bulk and its dosage form. The methods' greenness was assessed via three tools: the green analytical procedure index (GAPI), analytical eco-scale, and analytical greenness assessment (AGREE).

A comparative study of green solid contact ion selective electrodes for the potentiometric determination of Letrozole in dosage form and human plasma.

Analysis of drugs clinically and their identification in biological samples are of utmost importance in the process of therapeutic drug monitoring, also in pharmacokinetic investigations and tracking of illicit medications. These investigations are carried out using a variety of analytical methods, including potentiometric electrodes. Potentiometric electrodes are a wonderful solution for researchers because they outperform other methods in terms of sustainability, greenness, and cost effectiveness. In the current study, ion-selective potentiometric sensors were assembled for the aim of quantification of the anticancer drug Letrozole (LTZ). The first step was fabrication of a conventional sensor based on the formation of stable host-guest inclusion complex between the cationic drug and 4-tert-butylcalix-8-arene (TBCAX-8). Two additional sensors were prepared through membrane modification with graphene nanocomposite (GNC) and polyaniline (PANI) nanoparticles. Linear responses of 1.00 × 10-5-1.00 × 10-2, 1.00 × 10-6-1.00 × 10-2 and 1.00 × 10-8-1.00 × 10-3 with sub-Nernstian slopes of 19.90, 20.10 and 20.30 mV/decade were obtained for TBCAX-8, GNC, and PANI sensors; respectively. The developed sensors were successful in determining the drug LTZ in bulk powder and dosage form. PANI modified sensor was used to determine LTZ in human plasma with recoveries ranging from 88.00 to 96.30%. IUPAC recommendations were followed during the evaluation of the electrical performance of the developed sensors. Experimental conditions as temperature and pH were studied and optimized. Analytical Eco-scale and Analytical GREEness metric were adopted as the method greenness assessment tools.

The first validated stability-indicating HPLC/DAD method for quantitation of Vericiguat in its pharmaceutical formulation; Application to degradation kinetic studies.

The stability of innovative drug formulations and the development of appropriate stability-indicating methods remain major focuses of recent pharmaceutical analysis. In the present study, an efficient stability-indicating HPLC-DAD technique has been described and validated for the determination of Vericiguat (VER); a novel oral soluble guanylate cyclase (sGC) stimulator used in heart failure. VER's stability under various stress conditions was examined. It was shown that VER was sensitive to alkaline, oxidative and thermal degradation. Mass spectrometry (MS) in electrospray ionization mode was performed to figure out the structure of the alkaline and oxidative degradation products. Efficient separation of VER and its induced degradation products was accomplished using isocratic elution mode on the Inertsil ODS-C18 column. The mobile phase composed of water: acetonitrile (70:30 v/v) with 0.1% O-phosphoric acid; pH was adjusted to 2.22 and a flow rate of 0.80 mL/min. VER was detected at 332 nm over a concentration range of 2.00-20.00 µg/mL. The retention time was 4.500 ± 0.005 min and the correlation coefficient was 0.9996. Following the International Conference of Harmonization's guidelines, the analysis was validated to be specific, fast, simple, precise and accurate for utilization in routine analysis and quality control of VER in its pharmaceutical formulation. Additionally, the suggested technique was expanded to investigate the kinetics of alkaline, oxidative and dry heat degradation.

Solid-state ion-selective electrodes for the first potentiometric determination of the anti-COVID 19 drug Remdesivir in human plasma; A comparative study.

Establishing sensitive and targeted analytical methodologies for drug identification in biological fluids as well as screening of treatments that can counteract the most severe COVID-19 infection-related side effects are of utmost importance. Here, first attempts have been made for determination of the anti-COVID drug Remdesivir (RDS) in human plasma using four potentiometric sensors. Calixarene-8 (CX8) was used as an ionophore applied to the first electrode (Sensor I). The second had a layer of dispersed graphene nanocomposite coating (Sensor II). (Sensor III) was fabricated using nanoparticles of polyaniline (PANI) as ion-to-electron transducer. A reverse-phase polymerization using polyvinylpyrrolidone (PVP) was employed to create a graphene-polyaniline (G/PANI) nanocomposite electrode (Sensor IV). Surface morphology was confirmed by Scanning Electron Microscope (SEM). UV absorption spectra and Fourier Transform Ion Spectrophotometry (FTIR) also supported their structural characterization. The impact of graphene and polyaniline integration on the functionality and durability of the manufactured sensors was examined using the water layer test and signal drift. In the ranges of concentration of 10-7 to 10-2 mol/L and 10-7 to 10-3, sensors II & IV exhibited linear responses; respectively while sensors I & III displayed linearity within 10-6 to 10-2 mol/L. The target drug was easily detectable using LOD down to 100 nmol/L. The developed sensors satisfactorily offered sensitive, stable, selective and accurate estimate of Remdesivir (RDS) in its pharmaceutical formulation as well as spiked human plasma with recoveries ranging from 91.02 to 95.76 % with average standard deviations less than 1.85. The suggested procedure was approved in accordance with ICH recommendations.

Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance.

To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.

Dietary supplement mislabelling: case study on selected slimming products by developing a green isocratic HPLC method for their quality control.

Nowadays, a huge population consumes Dietary supplements for losing weight. Products are often claimed as botanical blends, yet they aren't necessarily safe. Misleading labels are also very common. Thus, validated analytical methods for a wide range of slimming compounds are highly needed. Herein, we present a simple HPLC/PDA method for the quantitation of seven popular slimming ingredients. Studied compounds were Caffeine, Raspberry Ketone, trans-Resveratrol, p-Synephrine, p-Octopamine, p-Hordenine and 2-phenethylamine. After optimization, separation was carried out on a C18 column and mobile phase was a mixture of Acetonitrile:Water containing 0.1% phosphoric acid (50:50, %v/v). The last compound was eluted at 9.76 min. Separation was efficient showing baseline- separated symmetric peaks, without using any gradient programs, organic mobile phase modifiers or modified stationary phases. Method validation was done following ICH guidelines. Calibration curves were linear over wide concentration ranges and calculated LOD values were in the range 0.02-0.09 µg/mL. Method greenness was assessed using Analytical Eco-scale, GAPI and AGREE metric tools. Further, four random sample products purchased from online supplement stores were assayed. Results proved some mislabeling actions. To support our findings, standard addition was carried out and average % recoveries were 96.67 - 101.44% with standard deviation ≤ 2.83 between measurements.

A validated UHPLC-MS/MS method for simultaneous quantification of some repurposed COVID-19 drugs in rat plasma: Application to a pharmacokinetic study.

Since the emergence of Corona virus disease (COVID-19) in 2019, a number of medications have been developed and tried to combat the pandemic. In the present study, we develop a LC-MS/MS approach to detect and quantify certain COVID-19 candidate drugs in rat plasma, including Hydroxychloroquine, Favipiravir, Oseltamivir, and Remdesivir. The analytes were separated using Ultra High-Pressure Liquid Chromatography (UHPLC) over a 13-minute run on a C18 column. The extraction solvent for the (QuEChERS) quick, easy, cheap, effective, rugged and safe method was methanol, while the clean-up phase was primary secondary amine (PSA). Satisfactory recoveries were achieved for all compounds ranging from 82.39 to 105.87 %, with standard deviations smaller than 15.7. In terms of precision, accuracy, linearity, matrix effect, and stability, the method was validated according to US FDA criteria. The Limit of Detection (LOD) was determined to be between 0.11 and 10 ppb. The approach was further developed for a modest pharmacokinetic research in laboratory rats, and thus can be suitable for therapeutic drug monitoring in clinical cases under the same treatment.

Investigation of a QuEChERS-Based Method for Determination of Polycyclic Aromatic Hydrocarbons in Rat Plasma by GC-MS.

Owing to the toxic effects of polycyclic aromatic hydrocarbons (PAHs) on humans and the environment, their sensitive biomonitoring is essential and significant. In this work, a sensitive, simple and rapid bioanalytical method was established for the simultaneous determination of 13 PAHs in rat plasma depending on QuEChERS (Quick, easy, cheap, effective and rugged method) as a preliminary step and gas chromatography-mass spectrometry (GC-MS) for identification. QuEChERS procedure was optimized where acetonitrile was employed for plasma samples extraction, which was further cleaned using primary secondary amine as the sorbent material. Optimization of GC-MS conditions was performed to produce optimum selectivity of the proposed method. The method was fully validated for rat plasma samples where recoveries, matrix effects, limit of quantitation (LOQ), linearity and precision were evaluated. Linearity range was 5-100 ng/mL for most of the 13 analytes. Average recoveries of the 13 PAHs ranged between 85.57% and 109.64% in fortified rat plasma with standard deviations <8.91 except for anthracene that showed 19.24. The limits of detection and LOQs for the 13 compounds ranged from 0.045 to 0.372 ppb and from 0.137 to 1.128 ppb, respectively. The established method was successfully implemented to perform a minor toxicokinetic study in intraperitoneally dosed rats (0.25 and 2 mg/kg in vegetable oil). The 13 PAHs were tracked in rat plasma samples for 6 h after administration, and most of the target compounds were recognized in plasma samples only at the higher dose.

Acute Invasive Fungal Rhinosinusitis and Coronavirus Disease 2019.

ABSTRACT: Acute invasive fungal rhinosinusitis (mucormycosis) is a rare, highly fatal disease. This opportunistic fungal infection causes angioinvasion and ischemic tissue necrosis. It mainly affects immunocompromised patients. Since the coronavirus disease 2019 (COVID-19) outbreak, many case reports have described the rhino-orbital-cerebral mucormycosis associated with COVID-19. However, the underlying predisposing factors are unknown. Several factors, other than diabetes, which is the most well-known contributing factor, may be involved in causing this severe fungal infection in COVID-19 patients. These factors may include steroid therapy, which is being used in severely dyspneic patients, the use of broad-spectrum antibiotics that may cause fungal flare-ups, and hospitalization with possible nosocomial infections. In addition, increased serum ferritin levels, possible endothelial damage, and pancreatic islets affection among COVID-19 patients may be implicated. Head and neck surgeons should be aware of the increasing prevalence of craniofacial mucormycosis among COVID-19 patients, as early diagnosis and prompt treatment are essential to improve the outcomes.

DNA integrity in diagnosis of premalignant lesions / Integridad del ADN en el diagnóstico de lesiones premalignas

Background: Carcinogenesis is a dynamic process which traditional biopsying can not keep up with. Saliva asfluid in the vicinity of the tumor can offer better insights to this process. This study aimed to identify the accuracyof salivary DNA integrity index in differentiating between oral premalignant lesions and oral cancer.Material and Methods: This phase II diagnostic test accuracy study included 93 patients divided into three groups:30 oral cancer patients, 33 patients with oral premalignant lesions divided into 21 oral lichen planus patients and12 patients with leukoplakia and 30 normal individuals who acted as controls. Oral rinse was collected from allparticipants and they all underwent conventional visual and tactile examination, and patients with oral lesions hadthe diagnosis confirmed by histopathological examination of tissue biopsy. DNA integrity index was determinedas the ratio between ALU247 and ALU115 measured by qPCR.Results: There was no statistically significant difference regarding ALU115, ALU247 and DNA integrity indexbetween the three study groups. The index was significantly higher in the oral cancer group than the oral lichenplanus patients, while no significant difference was found between the oral cancer and the leukoplakia cases. TheDNA integrity index sensitivity, specificity, positive and negative predictive values were 73%, 45%, 55% and 65%respectively.Conclusions: Salivary DNA integrity index showed poor diagnostic abilities in differentiating between the oralcancer and premalignant lesions.(AU)

Quality control of dietary supplements: An economic green spectrofluorimetric assay of Raspberry ketone and its application to weight variation testing.

Although Dietary supplements are readily accessible and extensively used worldwide, they are inadequately regulated and consumers are victims of manufacturers' fraud. Thus, quality regulations are required to ensure safety of products available to the public. We propose the first native spectrofluorimetric quality control assay of raspberry ketone, a popular dietary supplement ingredient for weight loss. This work relies on the constant wavelength synchronous scan of the Raspberry Ketone native fluorescence, overcoming the demerits of conventional excitation/ emission spectra. For the best measurement conditions, several parameters were optimized including Δλ value, diluting solvent, medium pH and the effect of surfactants/ macromolecules. In aqueous medium (Δλ = 110 nm), a linear relationship exists between synchronous fluorescence intensity at peak maximum 405.6 nm and solution concentration in the range 300-1500 ng/mL. Method sensitivity was recorded with LOD and LOQ values 60.63 and 183.72 ng/mL; respectively. Validation was done in accordance to International Conference on Harmonization (ICH) guidelines. This simple procedure was successfully applied to the analysis of Raspberry Ketone in commercially available dietary supplement capsules with average recovery 98.67% ± 1.74 and further extended to weight variation testing following the official United States Pharmacopeial (USP) guidelines. Finally, green assessment was done using the ''Analytical Eco-scale'' tool. The total score was 89/100 points revealing excellent greenness of our proposal. Our proposal is simple, eco-friendly and cheap. It can be conveniently adopted for routine quality control practices especially in developing countries.

Subjective Smell Assessment as An Office-based Rapid Procedure In COVID-19 Era.

ABSTRACT: A recent history of smell disorder may be a potential predictor for COVID-19. The authors used a subjective olfaction score that was demonstrated on a hard paper-bar. The authors examined 480 patients who were attending the outpatient clinic. Ninety-seven patients (20.2%) demonstrated variable degrees of recent smell disorder. For those patients, lab testing including nasopharyngeal swab for real-time polymerase chain reaction (RT-PCR) was performed. Eighty-eight of them (90.7%) have been confirmed to be COVID-19 positive. Although psychophysical testing is more reliable, subjective assessment of smell is a rapid procedure and can be used as an office-based method for patients' screening in COVID-19 era. Smell disorder could be an alarming sign for COVID-19 even with absent characteristic symptoms.

Interferon gamma and interleukin 8 gene polymorphisms in patients with hepatitis C virus related oral lichen planus.

OBJECTIVES: This study aimed to determine the association of rs2430561 and rs4073 polymorphisms in the Interferon gamma (IFN-ɤ) and Interleukin 8 (IL-8) genes, respectively, with hepatitis C virus-related oral lichen planus and disease severity. DESIGN: This is a case-control study. 60 subjects were equally divided into patients with and without oral lichen planus. They were further subdivided into hepatitis C virus seropositive and seronegative patients. All patients were genotyped for IFN-γ rs2430561 thymine to adenine (T > A) and IL-8 rs4073 adenine to thymine (A > T) polymorphisms. All patients with oral lichen planus had their lesions measured and documented using the Escudier scoring system. RESULTS: Disease activity was significantly higher in the "oral lichen planus/hepatitis C virus-positive" patients than in the "oral lichen planus/hepatitis C virus-negative" patients (P = 0.003). IFN-γ rs2430561 T > A and IL-8 rs4073 A > T genotypes and allele frequencies were not associated with the oral lichen planus group or the normal group. Stratification of the two groups into HCV and non-HCV-infected patients or into erosive and non-erosive types revealed no significant associations. The "A-allele-containing" genotypes of IL-8 rs4073 A > T were significantly more prevalent in the patients with oral lichen planus than in those without. CONCLUSION: Hepatitis C virus infection is associated with the development of erosive oral lichen planus. The A-allele of IL-8 rs4073 A > T may have a role in the development and progression of oral lichen planus.

Cervical osteophytosis and spine posture: contribution to swallow disorders and symptoms.

PURPOSE OF REVIEW: The article reviews the effects of cervical osteophytosis and spine posture on swallowing, and how they can cause dysphagia. RECENT FINDINGS: Cerivical osteophytosis which is a bony overgrowth of the cervical spines, it affects the swallowing through different mechanisms, including direct mechanical compression of the pharynx and esophagus, disturbances of normal epiglottic tilt over the inlet of the larynx by the osteophytes at C3-C4 level, inflammatory reactions in the tissues around the esophagus and cricopharyngeal spasm. Also, cervical spine posture in normal individuals could affect the swallowing mechanism by disturbance of the sphincteric action of the larynx and upper esophageal sphincter. SUMMARY: Cervical osteophytosis and abnormal cervical curvature may be overlooked by the Otolaryngologists as causes of swallowing disorders. The diagnosis is usually confirmed by radiologic study for the cervical spine. Cervical abnormality should be kept in mind while we are investigating patients with swallowing problem, and postural modification may help in treatment of such cases.

Novel potentiometric sensors for the determination of the dinotefuran insecticide residue levels in cucumber and soil samples.

Five new potentiometric membrane sensors for the determination of the dinotefuran levels in cucumber and soil samples have been developed. Four of these sensors were based on a newly designed molecularly imprinted polymer (MIP) material consisting of acrylamide or methacrylic acid as a functional monomer in a plasticized PVC (polyvinyl chloride) membrane before and after elution of the template. A fifth sensor, a carboxylated PVC-based sensor plasticized with dioctyl phthalate, was also prepared and tested. Sensor 1 (acrylamide washed) and sensor 3 (methacrylic acid washed) exhibited significantly enhanced responses towards dinotefuran over the concentration range of 10-7-10-2molL-1. The limit of detection (LOD) for both sensors was 0.35µgL-1. The response was near-Nernstian, with average slopes of 66.3 and 50.8mV/decade for sensors 1 and 3 respectively. Sensors 2 (acrylamide non-washed), 4 (methacrylic acid non-washed) and 5 (carboxylated-PVC) exhibited non-Nernstian responses over the concentration range of 10-7-10-3molL-1, with LODs of 10.07, 6.90, and 4.30µgL-1, respectively, as well as average slopes of 39.1, 27.2 and 33mV/decade, respectively. The application of the proposed sensors to the determination of the dinotefuran levels in spiked soil and cucumber samples was demonstrated. The average recoveries from the cucumber samples were from 7.93% to 106.43%, with a standard deviation of less than 13.73%, and recoveries from soil samples were from 97.46% to 108.71%, with a standard deviation of less than 10.66%. The sensors were applied successfully to the determination of the dinotefuran residue, its rate of disappearance and its half-life in cucumbers in soil in which a safety pre-harvest interval for dinotefuran was suggested.

Swallowing disorders among patients with diffuse idiopathic skeletal hyperostosis.

CONCLUSION: Diffuse idiopathic skeletal hyperostosis (DISH) is a cause of swallowing disorders in elderly, and otolaryngologists should be aware of the disease on dealing with old patients complaining of dysphagia. The condition may be treated conservatively in most patients; however, surgical reduction of cervical osteophytes may be needed in severe cases. OBJECTIVE: Large cervical osteophytes may cause dysphagia; they compress the pharynx leading to mechanical impairment of swallowing. DISH is characterized by ossification of the anterior longitudinal spinal ligament with formation of osteophytes. The aim was to investigate swallowing disorders among patients with DISH. METHOD: The study included 139 patients with DISH. Their swallowing was evaluated using the eating assessment tool (EAT-10), and patients with swallowing disorders were subjected to fiber-optic endoscopic evaluation of swallowing (FEES), they received conservative treatment for 6 months. Patients were assessed again after treatment using the same measures that were employed before treatment. RESULTS: Twenty-three patients (16.5%) demonstrated swallowing disorder, and FEES showed residues of food in the pharynx after swallow in all of them. Significant overall improvement after conservative treatment was achieved, with two patients resuming their normal regular diet. However, one patient demonstrated no improvement, and he needed surgical reduction of his large cervical osteophytes.