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A green, sensitive and rapid spectrofluorimetric method for quantitative assay of an anti-allergic medication composed of montelukast and fexofenadine mixture in raw materials and dosage form was developed. The method was based on measuring the synchronous fluorimetric peak without interference, pre-separation or pre-extraction procedures. Montelukast was analyzed at 360 nm while fexofenadine was measured at 263 nm using Δλ = 20 nm for both drugs using ethanol as diluting solvent and acetate buffer of pH 4. The assay was rectilinear over the concentration range of 1.0-10.0 µg/mL for fexofenadine and 0.1-0.6 µg/mL for montelukast. The method was full validated according to ICH guidelines. The applicability of the method enables the assay of both drugs in raw materials, synthetic mixture as well as combined tablets. Moreover, the greenness of the method was assessed using different methods including; analytical eco-scale, GAPI and AGREE. All of these methods confirm that the proposed method is an eco-friendly method.

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In this work, the binding mechanism between donepezil (DNP) and bovine serum albumin (BSA) was established using several techniques, including fluorimetry, UV- spectrophotometry, synchronous fluorimetry (SF), fourier transform infrared (FTIR), fluorescence resonance energy transfer (FRET) besides molecular docking study. The fluorescence quenching mechanism of DNP-BSA binding was a combined dynamic and static quenching. The thermodynamic parameters, binding forces, binding constant, and the number of binding sites were determined using a different range of temperature settings. Van't Hoff's equation was used to calculate the reaction parameters, including enthalpy change (ΔHο) and entropy change (ΔSο). The results pointed out that the DNP-BSA binding was endothermic. It was shown that the stability of the drug-protein system was predominantly due to the intermolecular hydrophobic forces. Additionally, the site probing method revealed that subdomain IIA (Site I) is where DNP and BSA's binding occurs. This was validated using a molecular docking study with the most stable DNP configuration. This study might help to understand DNP's pharmacokinetics profile and toxicity as well as provides crucial information for its safe use and avoiding its toxicity.

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Coronavirus disease 2019 (COVID-19) is a contagious viral infection caused by coronavirus 2 (SARS-CoV-2) that causes severe acute respiratory syndrome. It has ravaged several countries and burdened many healthcare systems. As the process of authorizing a novel treatment for human use is extensive and involves multiple phases to obtain safety information and identify potential concerns. Therefore, the fastest and easiest choice was to use United States Food and Drug Administration (US FDA)-approved drugs such as favipiravir and hydroxychloroquine. For the simultaneous estimation of both medications, a simple synchronous spectrofluorimetric approach was established in which both drugs were measured at 372 and 323 nm, respectively in the presence of each other without interference at Δλ 60 nm. The effect of various experimental conditions on synchronous fluorescence intensities were thoroughly investigated and optimized. The maximum synchronous fluorescence intensities were obtained at pH 5.4 using acetate buffer (0.2 M, 0.5 ml) and ethanol as a diluent. Excellent linearity ranges were obtained using 1.0-18.0 ng/ml and 10.0-120.0 ng/ml for favipiravir and hydroxychloroquine, respectively. The approach exhibited high sensitivity with detection limits down to 0.25 ng/ml and 1.52 ng/ml and quantitation limits down to 0.77 ng/ml and 4.62 ng/ml, respectively. Spiking human plasma samples with the studied drugs yielded high % recoveries, allowing a significant bioanalytical application. Moreover, the method was validated according to International Conference on Harmonization guidelines and further applied to commercial pharmaceutical preparations with good results.

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A green, simple, quick and economical method is implemented for the first time for the simultaneous estimation of cetirizine (CTZ) and azelastine (AZE) as co-administered eye drops. The method relies on synchronous spectrofluorimetry with ∆λ = 60 nm. Cetirizine can be estimated at 231 nm and AZE can be measured at 294 nm, each at the other's zero crossing point. All factors affecting the method were studied and properly optimized. Good correlation was obtained in the range of 0.1-2 µg mL-1 for both drugs. The limits of detection were 0.014 and 0.010 µg mL-1 and limits of quantitation were 0.043 and 0.029 µg mL-1 for CTZ and AZE, respectively. Moreover, ICH guidelines were carried out to validate the adopted method. The method was suitable for the analysis of CTZ and AZE in synthetic mixtures, eye drops and aqueous humor. The mean percentage of recoveries of CTZ and AZE in spiked aqueous humor were 99.83 and 99.37, respectively. Furthermore, Green Analytical Procedure Index (GAPI) and analytical Eco-scale approaches were used to evaluate the greenness of the suggested method.

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Diabetes Mellitus is directly related to female anaphrodesia. Female Viagra or Flibanserin (FLB), U.S. FDA approved in 2015, is specifically indicated for premenopausal Hypoactive Sexual Desire Disorder, HSDD, which is one of the primary consequences of Diabetes Mellitus. Simultaneous analysis of the concomitantly administered, FLB and oral antidiabetics, as Sitagliptin phosphate (STG), is a crucial demand to investigate mutual drug-drug interaction. The latter is responsible for uncontrolled glycaemia and higher risk of sudden hypoglycemia. Two simple, sensitive, economical and direct analytical methods, namely, Second-Derivative Synchronous Fluorimetric Spectroscopy, D2-SFS, and High Performance Liquid Chromatography with fluorimetric detection, HPLC-FD, are established for simultaneous determination of FLB and STG in their binary mixtures. First method relies on measuring D2-SFS spectra of both drugs, at Δλ = 25 nm, along linearity ranges of 0.05-1 µg/mL for both drugs. The second method is a chromatographic one with gradient elution of FLB and STG on RP-ZORBAX Eclipse C18 column (5 µm, 4.6 × 150 mm). Mobile phase; phosphate buffer: acetonitrile, pH 4.5, with a flow rate of 1 mL/min at room temperature has been used. Time programmed fluorimetric detection is optimized at λem = 305 nm for STG (0.0-5.9 min), at λem = 375 nm for FLB (6-9 min) after both excitation at λex = 257 nm, in the linear ranges of 1-40 µg/mL and 5-60 µg/mL for FLB and STG, respectively. Proposed methods have been validated according to ICH guidelines, then applied for simultaneous quantitation of FLB and STG in their laboratory-prepared mixtures and in spiked human plasma samples. Satisfactory Student's t-value and F-variance ratio have been obtained upon comparing the results of both methods.

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Antineoplastic drugs, etoposide (ETO), are widely used in leukaemia. A patient with leukaemia has a relative infection with pneumonia treated by fluoroquinolones as moxifloxacin HCL (MOX). Because opioid analgesic as nalbuphine HCL (NAL) does not have a ceiling dose, it is used to manage the distasteful sensory in leukaemia. Consequently, green methods for synchronous spectrofluorimetric quantification of a ternary mixture of ETO, MOX and NAL were developed. The first approach relies simply on the estimation of MOX at 371 nm by conventional synchronous fluorimetric technique (Δλ of 60 nm). The second approach depends on applying the first derivative synchronous fluorimetric technique (Δλ of 60 nm) for simultaneous estimation of ETO and NAL at 257 and 273 nm, respectively. A good linear correlation was obtained in the ranges of 0.04-0.40, 0.10-1.00 and 0.50-5.00 µg ml-1 for MOX, ETO and NAL, respectively. Moreover, the proposed approaches were successfully applied for the estimation of the studied drugs in the pharmaceutical dosage forms. Additionally, the synchronous assessment of ETO, MOX and NAL in the spiked human urine was successfully attained by the facile protein precipitation technique. The mean % recoveries in spiked human urine were 99.49, 98.07 and 98.48 for MOX, ETO and NAL, respectively.

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In the present study, we conducted two facile and highly sensitive spectrofluorimetric approaches in order to quantify the vasoprotective agents; troxerutin (TROX) and calcium dobesilate (DOB) in the presence of hydroquinone (HQ) (as a highly toxic impurity and potential degradation product of DOB) in commercial formulations and human plasma. The first approach relies simply on using ethanol as an eco-friendly solvent for the estimation of DOB at 345 nm after being excited at 305 nm. The linearity was carefully investigated between DOB concentration and the relative fluorescence intensity in the range of 0.05-0.8 µg ml-1. Due to the high method simplicity and sensitivity, applying the first approach to quality control analysis and spiked human plasma samples with mean % recoveries 100.74 ± 3.71 adds another merit. The second approach involved rapid conventional fluorimetric estimation of ethanolic TROX solution in TROX/DOB combined dosage forms at 455/350 nm (emission/excitation) with a linear calibration chart covering the range of 0.1-1.2 µg ml-1. Moreover, the second approach involved a comprehensive study in a trial to solve the problem of superposition of DOB and HQ graph adopting the first derivative synchronous fluorimetric mechanism in ethanol at Δλ = 60 nm. Therefore, DOB was measured at 286 and 323 nm, while HQ could be quantitated at 301 nm. The Beer-Lambert Law has complied over the ranges of 0.1-1.0 and 0.02-0.4 µg ml-1 for DOB and HQ, respectively. Guidelines adopted by the International Council of Harmonization (ICH) were used to validate the target approaches. The developed methods are more convenient for routine quality control laboratory instead of the time-consuming and sophisticated reported techniques. Moreover, different aspects of evaluating the greenness of the proposed approaches were conducted to have a complete image of their environmental impact.

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Simeprevir (SMV) is commonly co-administered with ledipasvir (LDS) and sofosbuvir (SOF) as an effective combination regimen for treatment naive hepatitis C virus infected patients. In the present study, two spectrofluorimetric approaches were combined together for the development of highly sensitive, rapid, simple and accurate method for simultaneous quantification of SMV and LDS. The native fluorescence intensity values of SMV and LDS were enhanced by the addition of Tween-80 micellar system, while second derivative of the synchronous fluorescence intensity of the drugs at Δλ = 120 nm enabled the determination of both drug concomitantly. Different experimental parameters affecting the synchronous fluorescence of the cited drugs were carefully evaluated for their optimization. The peak amplitudes of the second derivative synchronous fluorimetry were measured at 429 nm for SMV and at 417 nm for LDS. The fluorescence-concentration plots were rectilinear over the range of 60-1500 and 36-540 ng mL-1 with lower detection limits of 9.0 and 6.0 ng mL-1 and quantification limits of 27.0 and 17.0 ng mL-1 for SMV and LDS respectively. The method was successfully applied for the determination of both drugs in their pure forms as well as their pharmaceutical products and human plasma without any significant interference. Statistical comparison with the reported method revealed excellent accuracy and precision of the proposed method.

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Propofol and cisatracurium besylate have been simultaneously determined using a highly sensitive first derivative synchronous spectrofluorometric method. The method is based on measuring first derivative synchronous spectrofluorimetric amplitude at Δλ = 40 nm with a scanning rate of 600 nm/min. The different experimental parameters affecting the fluorescence intensity of the two drugs were carefully studied and optimized. The amplitude-concentration plots were rectilinear over the range 40.0-400.0 ng/mL and 20.0-280.0 ng/mL for propofol and cisatracurium, respectively with lower detection limits of 4.0 and 2.35 ng/mL and quantification limits of 12.1 and 7.1 ng/mL for propofol and cisatracurium, respectively. The proposed method was successfully applied for the determination of the two compounds in synthetic mixtures and in commercial ampoules. The high sensitivity attained using the proposed method allowed the simultaneous determination of both drugs in spiked plasma samples. The mean % recoveries in spiked human plasma (n = 3) were 96.53 ± 0.90 and 96.20 ± 1.64 for each of propofol and cisatracurium, respectively. The method was validated in compliance with International Council of Harmonization (ICH) Guidelines.

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Sensitive, simple and green analytical methodology for simultaneous estimation of bambuterol and montelukast as a combined medication based on their native fluorescence character was developed. The method relies on synchronous spectrofluorimetry to solve the problem of the overlapping emission spectra of the studied drugs. Using second derivative synchronous spectra enabled the simultaneous quantitation of bambuterol and montelukast without interference. The peak amplitudes of the aqueous solutions at Δλ = 20 nm were estimated at 284 and 304 nm for bambuterol and at 374 and 384 nm for montelukast. A linear relationship was achieved over the concentration range of 0.2-1.00 µg ml-1 for bambuterol and 0.4-2.00 µg ml-1 for montelukast. All factors and parameters were carefully studied to obtain the highest sensitivity and good precision of the proposed method. Additionally, the validation criteria were assessed in accordance with International Council of Harmonization (ICH) guidelines. The method was used for the estimation of both drugs in their raw materials, synthetic mixtures as well their combined tablets with good agreement between its results and those from the comparison method.

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A highly accurate and precise spectrofluorimetric method was established for quantitation of Gatifloxacin in pure material, pharmaceutical formulations and in the existence of its oxidative degradation product. The emission was recorded at 487 nm after the excitation at 290 nm. Using micelle, sodium dodecyl sulphate (SDS), enhanced fluorescence intensity of Gatifloxacin-SDS complex. The optimization of numerous experimental conditions was carried out. The improved emission showed a suitable linear correlation between derivative synchronous fluorescence power and concentration of Gatifloxacin over the range of 10 to 100 ng/mL with a determination coefficient equals 0.9996. Studying cytotoxicity and antimicrobial susceptibility for oxidative degradation product of Gatifloxacin was carried out using Gatifloxacin as a control. In comparison, the proposed method presented a superior sensitivity and enhanced stability over the reported method.

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Two highly sensitive, rapid, simple, economic and validated spectrofluorimetric methods have been developed for determination of Topiramate and Levetiracetam in pharmaceutical tablets and in human plasma. Topiramate and Levetiracetam were determined separately by derivatization using 4-Chloro-7-nitrobenzofuran-2-oxo-1,3-diazole (NBD-Cl) and measured spectrofluorimetrically. The Relative fluorescence intensities were measured at λem/ex of 547/465 nm and 551/465 nm for Topiramate and Levetiracetam, respectively. While a binary mixture of Topiramate and Levetiracetam were determined by the fourth derivative synchronous fluorescence measurement after their reaction with NBD-Cl. In this method, the fourth derivative synchronous spectra were estimated as peak to peak measurement at 493-497 and 490.5-495 nm corresponding with zero-contribution of Levetiracetam and Topiramate, respectively. Linearity ranges for Topiramate and Levetiracetam in both methods were found to be 0.15-1.2 and 0.2-1.5 µg/mL, respectively. The different experimental parameters affecting the fluorescence of the two drugs were carefully studied and optimized. The proposed methods were validated in terms of linearity, accuracy, precision, limits of detection and quantification and other aspects of analytical validation. The proposed methods were successfully applied for the determination of the investigated drugs in human plasma samples obtained from healthy volunteers after single oral administration of the two drugs.

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A novel method for the simultaneous determination of 9-ethylphenanthrene (9-EP), pyrene (Pyr) and 1-hydroxypyrene (1-OH-Pyr) in an aqueous solution using hydroxyl-propyl ß-cyclodextrin (HPCD) as a sensitizer has been established. The overlap of the conventional fluorescence spectra of these molecules is resolved using synchronous fluorescence spectrometry with the double scans method. The simultaneous quantitative determination of three compounds was carried out with Δλ=36 nm and Δλ=55 nm. The signals detected at these three wavelengths (i.e., 298 nm, 337 nm and 351 nm) vary linearly when the concentrations of 9-EP, Pyr and 1-OH-Pyr were in the range of 5.00×10(-8)-1.60×10(-6) mol L(-1), 2.00×10(-8)-1.80×10(-6) mol L(-1), and 2.00×10(-8)-1.20×10(-5) mol L(-1), respectively. The limits of detection (LOD) for 9-EP, Pyr and 1-OH-Pyr were 3.97×10(-9) mol L(-1), 5.25×10(-)(9) mol L(-1), 4.20×10(-9) mol L(-1), respectively, with relative standard deviations (R.S.D.) of 1.62%, 2.45% and 1.73% (n=9), respectively. The inclusion behaviors between HPCD and the guest molecules were observed by synchronous fluorimetry and the association constants for the 1:1 complexes with HPCD were determined. The binding and complexation energies for different orientations are discussed. The proposed method was successfully applied to the analysis of 9-EP, Pyr and 1-OH-Pyr in tap and lake water with good recoveries in the range of 92.9-110.0%.

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A rapid, simple, accurate and highly sensitive spectrofluorimetric method was developed for the simultaneous analysis of nebivolol hydrochloride (NEB) and amlodipine besylate (AML). The method was based on measuring the synchronous fluorescence intensity of the drugs at Δλ = 40 nm in methanol. Various experimental parameters affecting the synchronous fluorescence of the studied drugs were carefully studied and optimized. The calibration plots were rectilinear over concentration ranges of 0.05-1.5 µg/mL and 0.5-10 µg/mL for NEB and AML with limits of detection (LOD) of 0.010 and 0.051 µg/mL and limits of quantitation (LOQ) of 0.031 and 0.156, respectively. The peak amplitudes ((2) D) of the second derivative synchronous fluorimetry (SDSF) were estimated at 282 nm for NEB and at 393 nm for AML. Good linearity was obtained over the concentration ranges. The proposed method was successfully applied to the determination of the studied compounds in laboratory-prepared mixtures, commercial single and laboratory-prepared tablets. The results were in good agreement with those obtained using the comparison method. The mean percent recoveries were found to be 100.12 ± 0.77 and 99.91 ± 0.77 for NEB and AML, respectively.

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A new synchronous fluorimetry in the combination with the photochemically induced fluorescence (PIF) method for simultaneous determination of nitrosodiphenylamine (NDPhA) and diphenylamine (DPhA) in aqueous and methanolic solution has been proposed. DPhA has a variety of applications and NDPhA is carcinogenic product of its. The method is based on the use of UV irradiation to produce fluorescent derivatives from NDPhA as a non-fluorescent molecule. The PIF properties of these amines in three media (water, methanol and acetonitrile) are reported. Because of their similar features, the fluorescence emission spectra of NDPhA photoproducts and DPhA were found to severely overlap in the whole wavelength region. Overlapping of conventional fluorescence spectra of these molecules is resolved by synchronous fluorometry using double scans method (SF-DS), thus making the use of separation techniques unnecessary for simultaneous determination of NDPhA and DPhA. The synchronous fluorescence intensity of NDPhA was measured at Δλ of 127 nm and at Δλ=75 nm for DPhA in solution, which are independent of each other. The best sensitivity can be achieved in water. The linear ranges for determination of NDPhA and DPhA were 1 × 10(-8) to 6 × 10(-6)molL(-1) and 4 × 10(-8) to 9 × 10(-6)molL(-1), and the limits of detection (LOD) were 8×10(-9) and 1 × 10(-8)molL(-1), respectively. The relative standard deviations (R.S.D.) of method is<3% (n=5). The proposed method was successfully applied for the determination of the two compounds in synthetic solutions, well water samples and also in gunpowder samples. The results obtained were favorably compared to those obtained with HPLC analysis.

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A rapid, simple and highly sensitive second derivative synchronous fluorometric method has been developed for the simultaneous analysis of binary mixture of chlorzoxazone (CLZ) and ibuprofen (IP). The method is based upon measurement of the synchronous fluorescence intensity of these drugs at Δλ=60 nm in methanol. The different experimental parameters affecting the fluorescence of the two drugs were carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the range of 0.2-4 µg/mL and 0.1-1.6 µg/mL for CLZ and IP, respectively with lower detection limits (LOD) of 0.028 and 8.3 × 10(-3) µg/mL and quantification limits (LOQ) of 0.086 and 0.03 µg/mL for CLZ and IP, respectively. The proposed method was successfully applied for the determination of the two compounds in synthetic mixtures and in commercial capsules. The high sensitivity attained by the proposed method allowed the determination of both drugs and real human plasma samples. The mean % recoveries in real human plasma (n=3) were 87.69 ± 6.15 and 92.57 ± 4.39 for each of CLZ and IP respectively.