Turn-on fluorescence of mirabegron for its sensitive detection in human plasma: Box-Behnken-Design for optimization.

Here, a novel fluorescence strategy was established for the detection of mirabegron (MBG) sensitively on the basis of hantzsch dihydropyridine synthesis. The developed method adopts turn-on fluorescence of MBG for the first time, permitting its selective determination in spiked human plasma at 486 nm after excitation at 410 nm. The developed method exhibited a good linear range from 0.5 µgmL-1 to 2.0 µgmL-1 with detection and quantification limits of 0.05 and 0.2 (µgmL-1), respectively. The profitable applicability of the developed method in spiked human plasma samples was demonstrated, achieving limit of detection below the previously levels reported by spectroscopic methods, allowing application of the developed method for selective determination of MBG in its tablets and spiked human plasma samples with good recovery.

Fine-tuning Fluorescence of Amlodipine Adopting on Blocking of Photoinduced Electron Transfer (PET): Application in Human Plasma.

Assessing medication adherence through the determination of antihypertensive drugs in biological matrices holds significant importance. Amlodipine (AP), a potent antihypertensive medication extensively prescribed for hypertensive patients, is particularly noteworthy in this context. This article aims to introduce a rapid, simple, improved sensitivity, and reproducibility in detecting AP in its pure form, tablet formulation, and spiked human plasma than the other reported methods. The proposed method utilizes a fluorescence approach, relying on the inhibition of the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom in the primary amino moiety of AP. This inhibition is achieved by acidifying the surrounding medium using 0.2 M acetic acid. By blocking PET, the target AP drug is sensitively detected, at [Formula: see text] 423 nm over a concentration range 25-500 ng mL- 1 showcasing an exceptionally low quantitation limit of 1.41 ng mL- 1. Notably, this innovative technique was successfully applied to detect AP in its solid dosage form and spiked human plasma. Remarkably, matrix interference was found to be insignificant, underscoring the robustness and applicability of the established approach. The combination of speed, sensitivity, and reproducibility makes this method particularly suitable for assessing medication adherence in patients prescribed AP for hypertension.

A unique implementation of Hantzsch reaction for determination of natamycin in Yoghurt: Hyphenated with Box-Behnken-design for optimization.

This study aims to develop a novel and selective method for the detection of natamycin (E235) in yoghurt. The suggested method adopts an application of Hantzsch reaction to turn on the fluorescence behavior of natamycin (blue fluorescence), allowing its sensitive and selective determination in yoghurt samples without any overlapping at 485 nm. The originality of the research lies in the fact that this application takes place for the first time, also the detection (LOD) and quantification (LOQ) limits were very low (0.02 and 0.06µg mL-1, respectively) with a linear concentration range of 0.1-1.0 µgmL-1. Moreover, the developed method was employed for the detection of E235 in yoghurt sample with a good recoveries (98.80 ± 1.20-99.20 ± 1.15 (%), over a concentration range of 0.5-1.0 µgmL-1, (LOD = 0.04 and LOQ = 0.12 µgmL-1). Furthermore, the specificity and convenient application of our intended method is an attempt to determine E235 in milk anddairy products with easily followable steps.

Green and inventive fluorescence approach for levodropropizine determination in human plasma.

A green, rapid and sensitive fluorimetric method to quantify levodropropizine (LVP) in human plasma was exploited for the first time. The proposed method adopts LVP's intrinsic fluorescence in distilled water at a detecting emission of 345 nm following excitation at 240 nm. LVP displayed linearity across concentrations ranging from 50 to 1000 ng mL-1, with a detection limit of 0.77 ng mL-1 and a quantification limit of 2.33 ng mL-1. Thorough validation confirmed its reliability, successfully determining LVP in tablets with an average recovery of 98.64 ± 1.07 %. Furthermore, the method's applicability extended to estimate the studied drug in spiked human plasma with excellent obtained percentage recoveries (98.68 ± 1.28-100.14 ± 1.23).

Improving fluorescence emission of cyproheptadine by hindering its intramolecular photoinduced electron transfer (PET): Application to content uniformity testing and human plasma.

The ability to determine antihistaminic drugs in biological matrices is critical for the medication adherence assessment. Among these antihistaminic medications, cyproheptadine (CPD); that is acting as a potent first-generation antihistaminic drug that has been extensively prescribed for allergic patients. Most of the established approaches for CPD detection are not appropriate for this purpose owing to their weak sensitivity, lack of rapidity, and complicated experimental procedures. Herein, we present a very fast, highly sensitive, and reproducible approach for the detection of CPD in its pure form, tablet formulation, and spiked human plasma. The photoluminescence approach depends on hindering the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom present on the piperidine ring of CPD by making the surrounding medium acidic using 1.0 M acetic acid. Based on blocking PET, the target CPD drug has been sensitively detected from 5.0 to 500 ng mL-1 with a very low detection and quantitation limit of 7.01 and 21.25 ng mL-1, respectively. Moreover, the established approach was used for checking the tablet content uniformity testing for each tablet and spiked human plasma, and noteworthy, the matrices interference was insignificant.

Tuning fluorescence of dapoxetine by blocking of photoinduced electron transfer (PET): Application in real human plasma.

Photoinduced electron transfer (PET) is the most common mechanism proposed to account for quenching of fluorophores. Herein, the intrinsic fluorescence of dapoxetine (DPX) hydrochloride is in the "OFF" state, owing to the deactivation effect of PET. When the amine moiety is protonated, the fluorescence is restored. Protonation of the nitrogen atom of the tertiary amine moiety in DPX leads to "ON" state of fluorescence due to hindrance of the deactivating effect of PET by protonation of the amine moiety. This permits specific and sensitive determination of DPX in human plasma [lower limit of quantification (LLOQ) = 30.0  ng mL - 1 ]. The suggested method adopts protonation of DPX using 0.25 M hydrochloric acid in anionic micelles [6.94 mM sodium dodecyl sulfate (SDS)] leads to a marked enhancement of DPX-fluorescence, after excitation at 290 nm.

Neurological Manifestations in Pediatric COVID-19 Patients Hospitalized at King Abdulaziz University Hospital, Jeddah, Saudi Arabia: A Retrospective Study.

There are limited data about neurological manifestations in pediatric COVID-19 patients from all over the world, including Saudi Arabia. This study was performed to identify characteristics of pediatric COVID-19 cases with neurologic involvement hospitalized at King Abdulaziz University Hospital (KAUH), Saudi Arabia. This retrospective cross-sectional study included hospitalized patients aged 0-19 years with confirmed SARS-CoV-2 from April 2020 to February 2022. The required data were retrieved from patients' medical records. Ninety-four cases were included. The median ages of the studied group, those with neurological manifestations, and those without neurologic manifestations, were 6.5, 11.0, and 5.0 years, respectively. Neurological manifestations occurred in 29 COVID-19 patients (30.9%) with headache and decreased consciousness being the most common recorded manifestations in 8.5% and 6.4% of patients, respectively. Specific neurological manifestations were rare, as only two infants developed encephalopathy with fatal outcome. Most patients with and without neurological manifestations survived. Neuroimaging abnormalities were detected in 8 cases with neurological manifestations. Neurological manifestations were common in 31% of hospitalized pediatric COVID-19 cases. However, most of the neurological manifestations were mild and nonspecific, with headache being the most common one. Specific neurological manifestations were rare; however, pediatric COVID-19 patients, particularly young infants, were at risk of developing severe encephalopathy with fatal outcome.

Green innovative fluorescence approach for the feasible and reliable assay of thiol-containing drugs; captopril as a model.

In the present study, a novel spectrofluorimetric approach was designed for the analysis of captopril as a thiol-containing compound. The approach is based on the formation of a ternary fluorescent compound between the target thiol compound, ortho-phthaldehyde, and a suitable primary amine-containing compound. The produced 1-thio-alkyl-isoindole derivative exhibited very high emission activity in a faintly alkaline aqueous solution that could be monitored at 448 nm (excitation at 334 nm). 2-Amino-6-methyl-6-hydroxy-heptane was selected as the primary amine candidate that gave the high fluorescence intensity with the stability of the formed product. At the optimal experimental condition, the intensity of fluorescence of the formed product was linearly related to the concentration of captopril in 20-450 ng mL-1 range. Commercial pharmaceutical tablets were analyzed, and the obtained results agreed with those of the published method regarding precision and accuracy. The mechanism of the reaction was discussed. In addition, the greenness of the approach was rated following eco-scale criteria.

Micelle-enhanced spectrofluorimetric method for the rapid determination of bronchodilator terbutaline and its prodrug bambuterol: application for content uniformity test.

A novel, simple and sensitive spectrofluorimetric approach for determination of terbutaline sulphate (TER) and its prodrug bambuterol (BAM) in their pure and pharmaceutical dosage forms was developed. The suggested approach depends on enhancing the native fluorescence of either TER or BAM at 315 and 297.2 nm after excitation at 277 and 259 nm, respectively, using sodium dodecyl sulphate (SDS) as a micellar medium. In the presence of 0.7% w/v SDS, ~1.38-fold and 1.18-fold enhancement is achieved in the relative fluorescence intensity (RFI) of TER and BAM, respectively. The fluorescence-concentration curves were rectilinear over the concentration range 0.8-16 µg ml-1 , with detection limits (LOD) of 0.252 and 0.26 (µg ml-1 ), quantitation limits (LOQ) of 0.76 and 0.79 (µg ml-1 ), determination coefficients (r2) of 0.9981, and slopes of 45.92 and 10.44 for TER and BAM, respectively. The suggested approach was validated in accordance with International Council for Harmonisation criteria and was effectively applied in the analysis of the studied drugs in their commercial tablets. The high sensitivity of the proposed approach allows its application in evaluating the content uniformity testing of the studied drugs in their tablets through using the official United States Pharmacopeia criteria. Statistical analogies of the findings with that of the reported methods showed really good harmony and indicated no major differences in precision and accuracy.

Multisystem Inflammatory Syndrome in a 12-Year-old Boy After mRNA-SARS-CoV-2 Vaccination.

Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection is well known. We describe a 12-year-old child developing MIS-C after receiving 2 doses of mRNA COVID-19 vaccines without clinical evidence of COVID-19 infection. A possible association between the SARS-CoV-2 vaccine and MIS-C cannot be excluded.

HPTLC Method for the Ultrasensitive Detection of Triamterene in Plasma.

A high-performance thin-layer chromatographic (HPTLC) method has developed for the selective detection of a diuretic drug, triamterene (TRIAM), in pure form, tablets and human plasma. The method was based on chromatographic separation of TRIAM using HPTLC plates, precoated with silica gel, and a mobile phase consisted of ethyl acetate: dimethylformamide: ammonia (7.0: 2.7: 0.3, by volume). The native fluorescence signal of TRIAM was detected at 440 nm and used to quantify TRIAM using the proposed method, improving the method sensitivity to ~250-folds in comparison to that reported in previous HPTLC studies. The developed method enabled the detection of TRIAM in pure drug and biological samples (human plasma) within linear concentrations ranged from 0.8 to 60 ng/band or 1.0 to 60 ng/band for pure drug and plasma samples, respectively. Furthermore, the method was validated according to the official guidelines to permit its applicability in quality control and clinical laboratories.

A novel spectrofluorimetric method for determination of lomefloxacin adopting on zinc(II) chelation strategy: Application in human plasma.

A new sensitive and instantaneous spectrofluorimetric method for efficient determination of lomefloxacin (LMX) in its pure, dosage form and human plasma was designed. The developed method depends on formation of a metal-chelation compound of LMX as a ligand with zinc(II) in a buffer of acetate (pH 5.5). The following parameters; type of metal, concentration of metal, pH, type of buffer and diluting solvent were optimized. After carefully investigation; 0.2 mM zinc, 2.0 ml acetate buffer (pH 5.5) and water as diluting solvent were set as optimum reaction conditions. Under these conditions, a large increase in the intensity of the fluorescence of LMX was attained at 450 after excitation at 284 nm. The limits of detection and quantification were 5.8 and 1.9 ng ml-1 , respectively, with linearity range of 10.0 to 500.0 ng ml-1 . The binding mode of LMX and zinc(II) ion (Zn2+ ) was found to be 2:1, respectively, and confirmed by Job's plot method. Furthermore, it extended to the analysis of LMX in the spiked plasma of humans with percentage recovery (98.70 ± 0.97 to 100.30 ± 1.69%, n = 3).

Fear of COVID-19 and Its Impact on Job Satisfaction and Turnover Intention Among Egyptian Physicians.

INTRODUCTION: The risk of experiencing psychiatric symptoms related to the COVID-19 pandemic is high among healthcare workers whose occupations are in public health, emergency medicine, and intensive or critical care. MATERIALS AND METHODS: A cross-sectional study aimed to assess the prevalence of fear of COVID-19 among 411 frontline Egyptian physicians during the COVID-19 pandemic; identify determinants and predictors for fear of COVID-19; determine the impact of fear of COVID-19 on job satisfaction; and detect the impact of fear of COVID-19 on turnover intention. Three standardized scales (fear of COVID-19, job satisfaction, and turnover intention scores) were used for data collection via online Google Form. RESULTS: Regarding fear relating to the COVID-19 pandemic, 16.5% of the study subjects were classified as experiencing a severe fear level, while 78.1% experienced a moderate degree. A significant association between the level of fear relating to COVID-19 and the work department. The highest degree of fear is in a general-educational-university facility. Regarding job satisfaction, 42% of those having a severe level of fear are dissatisfied. Fear of COVID-19 is negatively associated with job satisfaction while positively significant correlated with turnover scores, a positive significant predictor of turnover intention. Job satisfaction is negatively associated with turnover intention; a negative significant predictor of turnover intention. CONCLUSIONS: Frontline Egyptian physicians reported higher levels of fear relating to the COVID-19 pandemic (moderate to severe). Increased fear levels relating to COVID-19 have a relationship with lower levels of job satisfaction and higher levels of job turnover.

Clinical characteristics and outcomes of children with COVID-19 in Saudi Arabia.

OBJECTIVES: To determine the demographic and clinical characteristics, underlying comorbidities, and outcomes of children with coronavirus disease 2019 (COVID-19) infection. METHODS: In this retrospective study, we reported 62 pediatric patients (age <14 years) with confirmed COVID-19 between March 2 and July 1, 2020, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. RESULTS: Comorbid conditions, including cardiac, neurological, respiratory, and malignant disorders, were reported in 9 patients (14.5%). The most prominent presenting complaints were fever (80.6%) and cough (48.4%). Most of our patients (80.6%) had mild disease, 11.3% had moderate disease, and 8.1% exhibited severe and critical illness. Twenty-one patients (33.9%) were hospitalized, with 4 patients (6.5%) admitted to the pediatric intensive care unit, and 3 (4.8%) patients died. CONCLUSION: All pediatric age groups are susceptible to COVID-19, with no gender difference. COVID-19 infection may result in critical illness and even mortality in subsets of pediatric patients.

Fear of COVID-19 and Its Impact on Job Satisfaction and Turnover Intention Among Egyptian Physicians

Materials and methods@#A cross-sectional study aimed to assess the prevalence of fear of COVID-19 among 411 frontline Egyptian physicians during the COVID-19 pandemic; identify determinants and predictors for fear of COVID-19; determine the impact of fear of COVID-19 on job satisfaction; and detect the impact of fear of COVID-19 on turnover intention. Three standardized scales (fear of COVID-19, job satisfaction, and turnover intention scores) were used for data collection via online Google Form. @*Results@#Regarding fear relating to the COVID-19 pandemic, 16.5% of the study subjects were classified as experiencing a severe fear level, while 78.1% experienced a moderate degree. A significant association between the level of fear relating to COVID-19 and the work department. The highest degree of fear is in a general-educational-university facility. Regarding job satisfaction, 42% of those having a severe level of fear are dissatisfied. Fear of COVID-19 is negatively associated with job satisfaction while positively significant correlated with turnover scores, a positive significant predictor of turnover intention. Job satisfaction is negatively associated with turnover intention; a negative significant predictor of turnover intention. @*Conclusions@#Frontline Egyptian physicians reported higher levels of fear relating to the COVID-19 pandemic (moderate to severe). Increased fear levels relating to COVID-19 have a relationship with lower levels of job satisfaction and higher levels of job turnover.

Prevalence of Workaholism Among Egyptian Healthcare Workers With Assessment of Its Relation to Quality of Life, Mental Health and Burnout.

Introduction: Work is a social double edged weapon activity that may have positive and negative effects on individual's quality of life and health. Objectives: To estimate workaholism prevalence and to determine its effects on quality of life, mental health, and burnout among healthcare workers (HCWs). Methods: Using a cross-sectional study, 1,080 Egyptian participants distributed as HCWs and non-HCWs were recruited. The study included 4 questionnaires to assess workaholism, quality of life (QoL), Psychological capital questionnaire (PCQ), and General health questionnaire (GHQ). Maslach Burnout Inventory (MBI) was applied to critical specialty HCWs in addition to pro-inflammatory markers including Il6, TNFα, and CoQ10. Results: This study revealed that 24.4 and 24.8% of HCWs were workaholic and hardworking, respectively, in comparison to 5.9 and 28.1% among non-HCWs (P < 0.001). Somatic symptoms and anxiety/ insomnia domains of GHQ were higher among HCWs than non-HCWs (P < 0.001 and 0.002, respectively). QoL was significantly lower among HCWs than non-HCWs (P < 0.001). Workaholism was reported among 43.2% of HCWs with critical specialty (P < 0.001). Components of PCQ components were significantly higher among HCWs with critical specialty than non-critical HCWs while QoL showed the reverse (P < 0.05). Working excessively was a predictor to burnout [Emotional exhaustion (ß = -0.23) and depersonalization (ß = -0.25)] and TNFα (ß = 0.41). Emotional exhaustion was a predictor to Il6 (ß = 0.66), TNFα (ß = 0.73), and CoQ10 (ß = -0.78). Conclusion: There is a significant association between workaholism and psychologically poor-health and poor quality of life among HCWs. Critical specialty healthcare workers showed association between workaholism, burnout and pro-inflammatory markers. Addressing of personal characteristics, supporting factors in the work environment and periodic examination of the healthcare workers and responding accordingly is required.

Mending the fluorescence of two α-blockers through a semiquinoid formation: Hyphenated with experimental design optimization.

Herein, a selective and rapid spectrofluorimetric method coupled with experimental design approach for reliable and efficient determination of two α-blockers, namely: terazosin hydrochloride (TER) and doxazosin mesylate (DOX) in their marketed tablets was developed. The presented method adopts formation of a semi-quinoid form of the studied drugs in borate buffer. The effects of parameters influencing fluorescence intensity including pH, the volume of buffer and diluting solvent were optimized using an experimental design methodology. The optimum conditions were found to be pH: 9.8, the volume of buffer: 2.0 mL and diluting solvent: water. Under the optimum experimental conditions, a large enhancement of the studied drugs fluorescence was obtained, measured at 387 after excitation at 246 nm for either TER or DOX with limits of detection 0.05 and 0.14 ng mL-1 and limits of quantification 0.14 and 0.43 ng mL-1 in the concentration ranges of 0.2-30.0 ng mL-1 and 0.5-30.0 ng mL-1 for TER and DOX, respectively. The presented method was validated according to the ICH guidelines. Furthermore, it extended to perform the content uniformity testing and analysis of the studied drugs in spiked human plasma with % recovery (96.00 ± 0.45-101.42 ± 1.20%, n = 3).

An efficient spectrofluorimetric method adopts doxazosin, terazosin and alfuzosin coupling with orthophthalaldehyde: Application in human plasma.

A new, selective and sensitive spectrofluorimetric method was designed for the quantitation of doxazosin (DOX), terazosin (TER) and alfuzosin (ALF) in their dosage forms and human plasma. The method adopts efficient derivatization of the studied drugs with ortho-phthalaldehyde (OPA), in the presence of 2-mercaptoethanol in borate buffer (pH9.7) to generate a highly fluorescent isoindole derivatives, which can strongly enhance the fluorescence intensities of the studied drugs, allowing their sensitive determination at 430nm after excitation at 337nm. The fluorescence-concentration plots were rectilinear over the ranges (10.0-400.0) ng/mL. Detection and quantification limits were found to be (0.52-3.88) and (1.59-11.76) ng/mL, respectively. The proposed method was validated according to ICH guidelines, and successfully applied for the determination of pharmaceutical preparations of the studied drugs. Moreover, the high sensitivity of the proposed method permits its successful application to the analysis of the studied drugs in spiked human plasma with % recovery (96.12±1.34-100.66±0.57, n=3). A proposal for the reaction mechanism was presented.

Innovative thin-layer chromatographic method combined with fluorescence detection for specific determination of Febuxostat: Application in biological fluids.

A newly developed thin-layer chromatographic (TLC) method coupled with fluorescence detection for specific determination of Febuxostat (FEB) was designed. The proposed method adopts exposure of FEB on a developed TLC plate to hydrochloric acid vapors, resulting in a large enhancement of its weak fluorescence, permitting its specific and sensitive determination in real human plasma and urine after excitation at 345nm on 60 F254 silica gel plates using toluene-ethyl acetate-methanol-glacial acetic acid; (30:10:5:0.1,v/v/v/v) as mobile phase. The retention factor (Rf) value for FEB was 0.33 ± 0.03 with a correlation coefficient of 0.9974 in the concentration range of 2.5-50ng/band. Upon using polynomial regression, the correlation coefficient was greatly improved (0.9999), with detection and quantification limits of 0.55 and 1.67 (ng/band), respectively. The proposed method was validated according to the International Conference of Harmonization and was successfully used for specific and selective determination of FEB in its commercial dosage form without excipient interference. Moreover, the proposed method was extended to efficient determination of the studied drug in real human plasma and urine samples in the presence of its metabolites without any interference, allowing clinical application of the proposed method for direct FEB determination in biological fluids as well as in pharmacokinetics studies and for quality control of the pharmaceutical dosage form without sample pretreatment or exhausting extraction steps.

Selective Spectrofluorimetric Method with Enhanced Sensitivity for Determination of Silodosine in Dosage Form and Human Plasma. Application to Stability Studies and Content Uniformity Testing.

A novel, sensitive and selective spectrofluorimetric method has been developed and validated for determination of silodosine (SLD) in its dosage form and human plasma. The method is based on nucleophilic substitution reaction of SLD with 5-(dimethylamino) naphthalene-1-sulfonyl chloride (dansyl chloride) in presence of 5.0 × 10-4 M sodium carbonate (pH 10.50) to yield a highly fluorescent derivative that was measured at 435 nm after excitation at 347 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence-concentration plot was rectilinear over the range 30.0-200.0 ng ml-1, with a correlation coefficient of 0.9979. The limits of detection (LOD) and quantification (LOQ) were found to be 5.44 and 16.47 ng ml-1, respectively. The proposed method was validated according to ICH guidelines, and successfully applied to the assay of commercial capsules as well as content uniformity testing. The high sensitivity of the proposed method allowed its successful application to the analysis of SLD in spiked human plasma with % recovery of 92.88 ± 1.05-100.73 ± 0.75%, (n = 6). The application of the proposed method was further extended to stability studies of SLD after exposure to different forced degradation conditions, such as acidic, alkaline and oxidative conditions, according to ICH guidelines, where this work describe the first attempt for selective spectrofluorimetric determination of silodosine in plasma and in the presence of its oxidative degradation.