Utility of Microwave-Synthesized Silver Nano Particles as Spectrofluorimetric Sensors for the Determination of Nano Concentrations of Favipravir: Application to Dosage Forms and Spiked Human Plasma.

A simple and facile microwave-assisted method was developed for the synthesis of highly fluorescent silver-nanoparticles (Ag-NPs). The synthesis of silver-nanoparticles depends on a redox reaction between silver nitrate and ascorbic acid using chitosan as a stabilizing agent. The produced Ag-NPs were characterized using Zeta potential and transmission electron microscope micrograph where they are spherical in shape with smooth surface morphology and size of 26.81 ± 2.2 nm. Favipiravir (FAV) was found to cause an obvious enhancement in the fluorescence of Ag-NPs; hence, they were used for its spectrofluorimetric estimation. The fluorescence intensity was measured at 430 nm after excitation at 360 nm. Under optimum conditions, a good linear relationship was accomplished between the FAV concentration and the fluorescence intensity in a range of (5.0-200.0) ng/mL with a limit of detection of 1.59 ng/mL. The method was successfully applied for the assay of the drug in its commercial tablets and spiked human plasma samples, and the results obtained were satisfactory.

Highly fluorescent nitrogen-doped carbon quantum dots prepared using sucrose and urea: Green synthesis, characterization, and use for determination of torsemide in its tablets and plasma samples.

A simple and facile microwave-assisted method was developed for the synthesis of highly fluorescent nitrogen-doped carbon quantum dots (N-CQDs) using sucrose and urea. The produced quantum dots exhibited a strong emission band at 376 nm after excitation at 216 nm with quantum yield of 0.57. The as-prepared N-CQDs were characterized using Fourier-transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM) images, and ultraviolet-visible (UV-visible) spectra. The average particle size was 7.7 nm. It was found that torsemide (TRS) caused an obvious quenching of the fluorescent N-CQDs; so, they were used for its spectrofluorometric estimation. An excellent linear correlation was found between the fluorescence quenching of N-CQDs and the concentration of the drug in the range of 0.10 to 1.0 µg/mL with limit of quantitation (LOQ) of 0.08 µg/mL and limit of detection (LOD) of 0.027 µg/mL. The method was successfully applied for the assay of the drug in its commercial tablets and spiked human plasma samples, and the results obtained were satisfactory. Complex GAPI was used for greenness assessment of the analytical procedures and the pre-analysis steps. Interference likely to be introduced from co-administered drugs was also studied.

Estimation of Two Diuretics Using Fluorescent Nitrogen Doped Carbon Quantum Dots: Application to Spiked Human Plasma and Tablets.

Highly fluorescent nitrogen doped carbon quantum dots (N-CQDs) were prepared by a single-step method based on microwave heating of cane sugar and urea. The produced N-CQDs were applied as nano-sensors for the spectrofluorimetric determination of eplerenone and spironolactone. A strong emission band at 376 nm was obtained after excitation at 216 nm due to the produced N-CQDs. The native fluorescence of N-CQDs was obviously quenched upon adding increased concentrations of each drug. A strong correlation was found between the fluorescence quenching of N-CQDs and the concentration of each drug. The method was found to be linear over the range of 0.5 to 5.0 µg/mL for eplerenone and 0.5 to 6.0 µg/mL for spironolactone with LOQ of 0.383 µg/mL and 0.262 µg/mL. The developed method was further extended for determination of both drugs in their pharmaceutical tablets and spiked human plasma. The results obtained were statistically compared with those of reported methods. The mechanism of fluorescence quenching of N-CQDs by the two drugs was discussed.

Greenness-by-design approach for developing novel UV spectrophotometric methodologies resolving a quaternary overlapping mixture.

Greenness-by-design (GbD) is an approach that integrates green chemistry principles into the method development stage of analytical processes, aiming to reduce their environmental impact. In this work, we applied GbD to a novel univariate double divisor corrected amplitude (DDCA) method that can resolve a quaternary pharmaceutical mixture in a fixed-dose polypill product. We also used a genetic algorithm as a chemometric modeling technique to select the informative variables for the analysis of the overlapping mixture. This resulted in more accurate and efficient predictive models. We used a computational approach to study the effect of solvents on the spectral resolution of the mixture and to minimize the spectral interferences caused by the solvent, thus achieving spectral resolution with minimal analytical effort and ecological footprint. The validated methods showed wide linear concentration ranges for the four components (1-30 µg/mL for losartan, 2.5-30 µg/mL for atorvastatin and aspirin, and 2.5-35 µg/mL for atenolol) and achieved high scores on the hexagon and spider charts, demonstrating their eco-friendliness.

An eco-friendly first and second derivative synchronous spectrofluorimetry for quantification of florfenicol in presence of its different degradation products. Application to kinetic stability study.

Two rapid, simple, sensitive and selective derivative spectrofluorimetric methods (first and second derivative synchronous spectrofluorimetric (FDSFS and SDSFS) procedures) have been developed for the analysis of florfenicol in the presence of its various degradation products. FDSFS was applied to assay the drug in the presence of its alkaline, oxidative and photolytic degradation products while SDSFS was used to quantify it in the presence of its acidic degradation product. These methods permitted quantification of florfenicol at corresponding λ Em of 288, 287, 279 and 284 nm without interferences from any of its degradation products. Full validation procedures were applied to the suggested method according to International Conference of Harmonization guidelines. Moreover, different degradation kinetic parameters were calculated such as half-life (t 1/2), degradation rate constant (K) and activation energy (E a). Using the analytical eco-scale, green analytical procedure index and analytical greenness metric approach AGREE as greenness assessment tools, the proposed method was found to be environmentally friendly.

Ecological spectroscopic methodologies for quantifying co-administered drugs in human plasma by photochemical quantum mechanical simulation.

Urinary tract infections (UTIs) constitute the second most prevalent bacterial infections in the elderly demographic. The treatment landscape involves various antibiotics targeting the causative organisms; nevertheless, the emergence of resistance significantly impacts therapeutic effectiveness. Presently, a fixed-dose pharmaceutical combination is advocated to optimize patient outcomes by mitigating the risks of bacterial resistance and associated side effects. Ofloxacin (OFL) and cefpodoxime proxetil (CPD) combinations, co-administered with flavoxate hydrochloride (FLV), have demonstrated efficacy in UTI cases, offering relief from concomitant symptoms. In the pharmaceutical market, fixed-dose combinations have gained prominence, driven by advantages such as enhanced patient medication adherence and compliance. In the realm of analytical chemistry, the integration of green practices in the initial phases of method development is exemplified by the Greenness by Design (GbD) strategy. While univariate spectroscopic methods are conventionally considered suboptimal compared to chemometric techniques for resolving intricate mixtures, GbD approach, when applied to UV spectroscopy, enable univariate methods to attain comparable or superior outcomes. GbD adopts a systematic approach to optimize experimental conditions, minimizing environmental impact and maximizing analytical performance. Critical to GbD applications in UV spectroscopy is solvent selection, influencing spectral resolution and measurement sensitivity. GbD employs a combination of in-vitro and in-silico experiments to evaluate solute-solvent interactions with underlying photochemical quantum phenomena affecting the resulting spectral morphology, identifying an optimal compromise solvent with high resolution and minimal ecological impact. Consequently, it facilitates the efficient resolution of spectral overlapping and determination of complex mixtures in UV spectroscopy using univariate methods. Comparative analysis with chemometric techniques, acknowledged as potent spectral resolving methods, demonstrated that GbD-based univariate methods performed equivalently. The methodology was validated according to ICH recommendations, establishing a linear quantitation range (2-30 µg/mL) and a limit of detection (0.355-0.414 µg/mL) for the three drugs in human plasma. The greenness of the developed methodology was affirmed through the AGREE assessment protocol, confirming its environmentally conscious attributes.

Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model.

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC0 - 24 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

Spectrofluorometric determination of cinacalcet hydrochloride: greenness assessment and application to biological fluids andin-vitrodissolution testing.

A facile, simple, green and sensitive spectrofluorometric method was developed for determination of the calcimimetic drug cinacalcet hydrochloride. It is used for the treatment of hyperparathyroidism. The drug showed high native fluorescence intensity at 320 nm after excitation at 280 nm. The method was linear over the range of 5.0-400.0 ng ml-1with excellent correlation (R2= 0.9999). Limit of detection (LOD) and limit of quantitation (LOQ) values were 1.19 and 3.62 ng ml-1, respectively. The percentage recovery was found to be 100.42% ± 1.39 (n=8). The proposed method was successfully applied for determination of cinacalcet in spiked human plasma samples with % recoveries of (87.23 to 109.69%). Two recent greenness metrics (GAPI and Analytical Eco-Scale) were chosen to prove the eco-friendly nature of the method. Furthermore, the proposed method was successfully applied to dissolution study of commercial cinacalcet tablets. The interference likely to be introduced by some commonly co-administrated drugs such as metoprolol and itraconazole was studied; the tolerance limits were calculated.

Use of green fluorescent nano-sensors for the determination of furosemide in biological samples and pharmaceutical preparations.

BACKGROUND: Carbon quantum dots (CQDs) are new class of carbon nanoparticles. Recently, they have been widely used as fluorescent probes due to their easy accessibility, optical properties and chemical inertness. Many available precursors are used in the synthesis of carbon quantum dots. The electrical and optical properties of CQDs could be enhanced by doping hetero atoms such as nitrogen or sulfur into their structure. OBJECTIVE: The current work presents the synthesis and characterization of water-soluble nitrogen doped carbon quantum dots (N-CQDs) and their use as fluorescent nano-sensors for the spectrofluorimetric determination of furosemide in its pharmaceutical preparations and spiked human plasma. METHODS: A domestic microwave was used to prepare the N-CQDs by heating a solution of sucrose and urea till complete charring (about ten minutes). The produced N-CQDs exhibit a strong emission band at 376 nm after excitation at 216 nm. Furosemide caused a quantitative quenching in the fluorescence intensity of the produced N-CQDs. RESULTS: The proposed method was validated according to ICH Guidelines. The method was found to be linear over the range of 0.1-1.0 µg/mL with LOQ of 0.087 µg/ml. CONCLUSION: Ecofriendly nano fluorescent sensors (N-CQDs) were successfully synthesized. The size of N-CQDs was distributed in the range of 6.63 nm to 10.23 nm with an average of 8.2 nm. The produced N-CQDs were used as fluorescent probes for the estimation of furosemide in its pharmaceutical preparations as well as spiked human plasma samples.

Eco-Friendly UV-Spectrophotometric Methods Employing Magnetic Nano-Composite Polymer for the Extraction and Analysis of Sexual Boosters in Adulterated Food Products: Application of Computer-Aided Design.

BACKGROUND: Solid phase extraction (SPE) techniques, based on computationally designed magnetic-based multi-targeting molecular imprinted polymer (MT-MIP), combined with UV spectrophotometric approaches provide advantages in the examination of counterfeit samples. OBJECTIVE: The current work describes an innovative and sustainable methodology for the simultaneous determination of tadalafil (TAD) and dapoxetine hydrochloride (DAP) in aphrodisiac counterfeit products (honey and instant coffee) utilizing SPE exploiting MT-MIP. Additionally, an innovative UV spectrophotometric method capable of resolving TAD in its pharmaceutical binary mixtures with DAP was developed. A novel computational approach was implemented to tailor the synthesis and design of the MT-MIP particles. METHODS: We applied a newly developed UV spectrophotometric method which was based on a Fourier self-deconvolution (FSD) method coupled with the isoabsorptive point for determination of TAD and DAP in pharmaceutical dosage form. We also applied an SPE process based on MT-MIP designed particles, assisting in the analysis of both drugs in counterfeit food samples. The SPE process and the UV spectroscopic methodology were assessed regarding their greenness using the pioneering green analytical procedure index (GAPI), analytical greeness including sample preparation (AGREEprep) and AGREE tools. The synthesized MT-MIP particles were characterized by scanning electron microscopy and energy-dispersive x-ray spectroscopy. RESULTS: The suggested spectrophotometric methods revealed a wide linear concentration range of 2-50 µg/mL with lower LODs in the range of 0.604-0.994 µg/mL. Additionally, the suggested method demonstrated the utmost sensitivity and eco-friendliness for their target in its mixed dosage form and counterfeit food products. CONCLUSION: The SPE process and the developed analytical UV spectroscopic methodology were validated as per the ICH guidelines, and were found to be suitable for overseeing some counterfeiting activities in commercially available honey and instant coffee aphrodisiac products. HIGHLIGHTS: An SPE method based on MT-MIP magnetic-based polymer and a UV spectroscopic method were successfully developed for analysis of TAD and DAP in different matrices.