An ingenious technique based on the usage of fluorone-based dye; pyrosin B in prucalopride assay in different matrices through an "on-off" dye native fluorescence probe.

Prucalopride (PCD), is a modern medication approved by the United States in 2018 to alleviate constipation caused by motility issues. PCD demonstrates a strong affinity and selectivity toward the 5-HT4 receptor. The study here introduces a feasible, direct, non-extractive, and affordable pathway for PCD analytical tracking. The fluorimetric study is based on the on-off effect on the emission amplitude of fluorone-based dye (pyrosin B). In a one-pot experiment, the complex between PCD and pyrosin B is formed instantly in an acidic medium. Correlation between decreased pyrosin B emission and PCD concentrations provides a linear calibration plot from 50 to 900 ng/mL. PCD-dye complex system affecting variables were meticulously tuned. The values of the estimated limit of quantitation and limit of detection for the current methodology were 47.5 and 15.7 ng/mL, respectively. Conformity of the strategy validity was achieved by a comprehensive study of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use criteria. The method was convincingly applied for PCD assay in tablets and content uniformity investigation. Furthermore, PCD tracking in the spiked biological fluid was applied. Finally, the method uses distilled water as dispersing medium which rise accommodation with the green chemistry principle.

A highly sensitive first derivative synchronous spectrofluorimetric approach for the simultaneous analysis of the anti-breast cancer co-administered drugs, letrozole and tramadol in dosage forms and human plasma at nanogram levels.

Letrozole is an anticancer medication prescribed for the management of estrogen receptor-positive breast cancer in postmenopausal women. Chronic pain is prevalent in patients receiving chemotherapy, leading to the use of adjuvant analgesics such as tramadol. This work introduces the first analytical approach for the concurrent quantification of letrozole and tramadol, two co-administered drugs, employing a rapid, highly sensitive, eco-friendly, and cost-effective first derivative synchronous spectrofluorimetric technique. The fluorescence of tramadol and letrozole was measured at wavelengths of 235.9 nm and 241.9 nm, respectively using a wavelength difference (Δλ) of 60.0 nm. The developed approach demonstrated exceptional linearity (r ˃ 0.999) within the specified concentration ranges for tramadol (10.0-1200.0 ng/mL) and letrozole (1.0-140.0 ng/mL). The results demonstrated that the proposed technique exhibits a high level of sensitivity, with detection limits of 0.569 and 0.143 ng/mL for tramadol and letrozole, respectively, indicating the good bioanalytical applicability. The within-run precisions, both intra-day and inter-day, for both analytes, were less than 0.71 % RSD. The developed approach was effectively applied to simultaneously estimate the mentioned drugs in their tablets and human plasma samples, achieving high percentage recoveries and low % RSD values. In order to assess the environmental sustainability of the developed approach, Analytical GREEnnessNNESS (AGREE) and the Green Analytical Procedure Index (GAPI) metric tools were employed. Both tools revealed that the developed approach is excellent green, suggesting its usage as an environmentally-friendly alternative for the routine assayof the investigated pharmaceuticals. The developed approach was validated according to the ICHQ2 (R1) requirements.

Facile and green chemistry-compatible fluorescence spectroscopic applications of acid red 87 used to evaluate eletriptan, antimigraine, in its pharmaceutical and biological samples.

Eletriptan (ETR), a selective pharmaceutical agent agonist of the 5-hydroxytryptamine1 receptor subtype, are primarily used to treat acute migraine attacks. ETR is a triptan-class medication that works by narrowing cerebral blood vessels and reducing chemicals that produce headache pain, light and sound sensitivity, and nausea. Due to its effectiveness in reducing migraine symptoms, it is a worthwhile choice for those looking for quick and efficient treatment. A green, raid, one-pot and straightforward fluorescence spectrometric method was employed to evaluate ETR in tablets and biological samples. By introducing the ETR drug and the fluorescent ligand, Acid red 87, in an acidic buffer, a quenching of the ligand native fluorescent was promptly produced. The quenching action was simply attributed to the selective ion-pair complex generation between the cationic target and the selected ligand. An increase in ETR concentration was linearly proportional to the quenching response in the 50.0 - 500.0 ng/mL range. The optimal configurations for adjusting the system's variable parameters were determined by examining the ETR-Acid red 87 system's response. Additionally, the sensor that was developed met the standards set by the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. The sensitivity thresholds of the approach were 13.8 and 42.0 ng/mL for the detection and quantification parameters, respectively, LOD and LOQ. This approach proficiently evaluated the pharmaceutical and biological samples of ETR. Finally, the proposed approach not only simplifies the analysis process but also limits the badimpact on the environment, making it a promising technique for analytical applications.

Isoquinoline-based intrinsic fluorescence assessment of erythropoiesis-stimulating agent, Roxadustat (FG-4592), in tablets: applications to content uniformity and human plasma evaluation.

In the present study, a first validated and green spectrofluorimetric approach for its assessment and evaluation in different matrices was investigated. After using an excitation wavelength of 345 nm, Roxadustat (ROX) demonstrates a highly native fluorescence at an emission of 410 nm. The influences of experimental factors such as pH, diluting solvents, and different organized media were tested, and the most appropriate solvent choice was ethanol. It was confirmed that there was a linear relationship between the concentration of ROX and the relative fluorescence intensity in the range 60.0-1000.0 ng ml-1, with the limit of detection and limit of quantitation, respectively, being 17.0 and 53.0 ng ml-1. The mean recoveries % [±standard deviation (SD), n = 5] for pharmaceutical preparations were 100.11% ± 2.24%, whereas for plasma samples, they were 100.08 ± 1.08% (±SD, n = 5). The results obtained after the application of four greenness criteria, Analytical Eco-Scale metric, NEMI, GAPI, and AGREE metric, confirmed its eco-friendliness. In addition, the whiteness meter (RGB12) confirmed its level of sustainability. The International Council for Harmonisation (ICH) criteria were used to verify the developed method through the study in both spiked plasma samples and content uniformity evaluation. An appropriate standard for various applications in industry and quality control laboratories was developed.

Innovative assembled optode device for enhanced in-situ ceric ions (Ce4+) evaluation and preconcentration in its real human, foods, water, and alloy samples.

Cerium (Ce) are the most widely distributed rare earth element. However, humans exposed to Ce through inhalation have been reported to experience heat sensitivity, itching, and heightened taste and odour perception. The present study aims to develop an optical sensor device with a short response time and high selectivity for Ce amongst other ions in various environments. The potential applicability of a 6-hydroxy-5-((4-hydroxy-2-methylphenyl)diazenyl)pyrimidine-2,4(1H,3H)-dione (HHMDPD) assembled ligand as aceric ion (Ce4+)-selective caption optode was examined. After generating an ion pair with Tetra-n-octylammonium bromide (TOABr) and immobilizing on a tri-acetyl cellulose (TAC) membrane, the solubility of the HHMDPD ligand is improved. The constructed optode membrane reacts with Ce4+ by turning its orange colour to violet in Thiel buffer (pH of 5.5), which can be detected spectrophotometrically at λmax 667 nm. The measurement linearity was in the range of 0.70 - 18.7 × 10-6 mol/L of Ce4+ concentration with detection and quantification limits of 0.23 × 10-6 and 0.70 × 10-6 mol/L, respectively. Whatever the Ce4+ concentration in its real samples, the response time of the constructed device was 5.0 min. Additionally, it recorded repeatability and reproducibility with a %RSD of 1.37 and 2.55, respectively (n = 3). The proposed optode device exhibited complete reversibility, for multiple measurements, which could be easily achieved with the aid of a solution of HCl, 0.01 mol/L. The applicability of the proposed device has been effectively extended to analyze synthetic mixes corresponding to different Ce4+ real human, foods, water, and magnesium-based Ce4+ alloys.

Integration of a facile sustainable resonance Rayleigh scattering switchable-based system for feasible determination of centrophenoxine, a nootropic and antioxidant agent; application to crude materials and dosage forms.

The proposed research adheres to a certain methodology to ensure that the technique used for analyzing the centrophenoxine drug is sustainable and green. It is important to highlight that several tools that have been recently developed were utilized as potential indicators of environmental sustainability and applicability. The present research presents a novel and entirely innovative method utilizing ultrasensitive spectrofluorimetry for the detection of centrophenoxine (CPX) drug. The employed methodology in this study involved the utilization of one-step, one-pot, and direct spectrofluorimetric technique, which was found to be both efficient and environmentally sustainable in the validation and assessment of the drug. Simply, when CPX and erythrosine B reagent were combined in an acidic environment, the highly resonance Rayleigh scattering product was immediately produced. The sensitivity limits were observed to be within the range of 15-47 ng mL-1, whereas the linearity was assessed to be in the range of 50-2000 ng mL-1. The optimal settings for all modifiable parameters of the system were ascertained through an analysis of centrophenoxine-erythrosine B complexes. Moreover, the system demonstrated compliance with International Council for Harmonization (ICH) specifications without encountering any issues. The suggested process was then rated on different recent environmental safety measuring metrics to see how good it was for the environment. Fortunately, the WAC standards that combine ecological and functional elements utilizing the Green/Red/Blue (RGB 12) design also acclaimed the current analytical technique as a white one. Additionally, a new applicability evaluation tool (BAGI) was employed to estimate the practicability of the planned method in the analytical chemistry field.

Synergistic utility of NBD-Cl fluorogenic loading activity and salting-out assisted liquid-liquid extraction as sample pretreatment in rasagiline tracking in different matrices.

A typical drug used to treat Parkinson's disease is called rasagiline. It belongs to an assortment of drugs known as monoamine oxidase inhibitors, which function by raising dopamine levels in the brain. This work created a unique spectrofluorimetric method for the analytical assay of rasagiline for the first time. The approach utilized the synergistic utility of the fluorogenic properties of benzofurazan and salting-out assisted liquid-liquid extraction. By combining these techniques an ultrasensitive, and highly selective methodology for the assay of rasagiline was established. Measurements were made of the resultant yellow fluorescent product at 533 nm by applying an excitation wavelength of 475.3 nm. The calibration graph was examined to assess its linearity across a range of 30-600 ng/ml. Through estimation, the limit of detection was discovered to be 8.9 ng/ml, while the quantitation limit was estimated to be 27 ng/ml. All relevant parameters influencing the fulfillment of the developed method were thoroughly examined and tuned. Following the directives set by the (ICH) the suggested approach was confirmed and demonstrated its capability for the accurate determination of rasagiline in tablets, as well as for testing content uniformity. The incorporation of salting-out assisted liquid-liquid extraction technology enables effective tracking of rasagiline in plasma samples, providing a novel and innovative approach for its analysis in biological matrices.

Tailored Tetrasubstituted Imidazole Carrying the Benzenesulfonamide Fragments as Selective Human Carbonic Anhydrase IX/XII Inhibitors.

A new series of tetrasubstituted imidazole carrying sulfonamide as zinc-anchoring group has been designed. The structures of the synthesized derivatives 5 a-l have been confirmed by spectroscopic analysis. These compounds incorporate an ethylenic spacer between the benzenesulfonamide and the rest of the trisubstituted imidazole moiety and were tested as inhibitors of carbonic anhydrases and for in-vitro cytotoxicity. Most of them act as effective inhibitors of the tumor-linked CA isoforms IX and XII, in nanomolar range. Also, different compounds have shown selectivity in comparable with the standard acetazolamide. Our IBS 5 d, 5 g, and 5 l (with Ki: 10.1, 19.4, 19.8 nM against hCA IX and 47, 45, 20 nM against hCA IX) showed the best inhibitory profile. In-vitro screening of all derivatives against a full sixty-cell-lined from NCI at a single dose of 10 µM offered growth inhibition of up to 45 %. Compound 5 b has been identified with the most potent cytotoxic activity and broad spectrum. Docking studies have also been implemented and were also in accordance with the biological outcomes. Our SAR analysis has interestingly proposed efficient tumor-related hCAs IX/XII suppression.

Guanidine dicycloamine-based analogs: green chemistry synthesis, biological investigation, and molecular docking studies as promising antibacterial and antiglycation leads.

Dicyandiamide (DCD) reacted with amino acids 1a-f to produce biguanides 2 and 4 and guanidine pyrazolones 3, 5, 6, 7, and 8, according to the reaction. DCD exhibited the following reactions: imidodicarbonimidicdiamide 9, diazocan-2-ylguanidine 10, methyl biguanidylthion 11, N-carbamothioylimidodicarbonimidicdiamide 12, 2-guanidinebenzoimidazole 13a, 2-guanidinylbenzoxazole 13b, and 2-guanidinylbenzothiazol 13c. These reactions were triggered by 6-amino caproic acid, thioacetamide, thiourea, o-aminophenol, o-aminothiophenol, and anthranilic acid, respectively. Compound 2 had the least antimicrobial activity, while compound 13c demonstrated the most antibacterial impact against all bacterial strains. Furthermore, in terms of antiglycation efficacy (AGEs), 12, 11, and 7 were the most effective AGE cross-linking inhibitors. Eight and ten, which showed a considerable inhibition on cross-linking AGEs, come next. Compounds 4 and 6 on the other hand have shown the least suppression of AGE production. The most promising antiglycation scaffolds 8, 11, and 12 in the Human serum albumin (HAS) active site were shown to be able to adopt crucial binding interactions with important amino acids based on the results of in silico molecular docking. The most promising antiglycation compounds 8, 11, and 12 were also shown to have better hydrophilicity, acceptable lipophilicity, gastrointestinal tract absorption (GIT), and blood-brain barrier penetration qualities when their physicochemical properties were examined using the egg-boiled method.

Utility of Cilefa Pink B, a foodstuff dye as a fluoro-substrate in the devising of the first facile green Molecular-mass-Related Fluorescence Sensor for quantifying amlodipine in batched material and dosage forms; content uniformity evaluation.

This study introduces the first and unique Molecular-mass-Related Fluorescence Sensor as the first fluorimetric strategy for determining amlodipine. An environmentally friendly, single-step, and direct spectrofluorimetric approach was utilized to evaluate the analyte. In an acidic setting, combining the amlodipine medication and the fluorescent dye Cilefa Pink B generated an instantaneous ultra-fluorescent product. An increase in dye response after adding amlodipine was proportional to the molecular weight of the generated complex, as measured at 329 nm. was the idea ofthe applied fluorimetric analysis. The complexing process increased the molecular mass from 879.86 to 1288.739 g mol-1. The medication's range of 0.050-1.00 µg mL-1 is directly correlated with this molecular massenlargement. The ideal settings for the changeable parameters of the system were established through an analysis of the response of the amlodipine-Cilefa Pink B system. Furthermore, the developed sensor complied with ICH (International Council for Harmonization) standards. The sensitivity limits were 0.0139 µg mL-1 (for the detection limit, LOD) and 0.042 µg mL-1 (for the quantification limit, LOQ). Additionally, this method effectively recovered the drug in its original and therapeutic dosage forms. Finally, the proposed process's environmental impact was also assessed through different modern greenness evaluation tools.

Self-ratiometric fluorescence approach based on plant extract-assisted synthesized silver nanoparticles for the determination of vanillin.

The current study designed and applied a novel self-ratiometric fluorescent nanosensor composed of green-synthesized silver nanoparticles (Ag-NPs) to determine vanillin in adult and infant foods and human plasma. A straightforward microwave-assisted approach is proposed for synthesizing Ag-NPs in less than 1 min using a reducing agent, tailed pepper seed extract. The synthesized Ag-NPs had a strong fluorescence with an intense emission band at 360 nm and a shoulder peak at 430 nm when excited at 265 nm. Upon interaction with vanillin, the fluorescence peak of Ag-NPs at 360 nm decreases in a concentration-dependent manner while being shifted to a longer wavelength, 385 nm. Meanwhile, the shoulder fluorescence peak at 430 nm is only slightly affected by vanillin addition. Thus, a new Ag-NP self-ratiometric probe was designed and validated for vanillin determination using the peak at 385 nm and the shoulder peak at 430 as two built-in reference peaks. The optimized system accurately measured vanillin with a detection limit of 9.0 ng/mL and a linear range of 0.05-8.0 µg/mL without needing pre-derivatization or high-cost instrumentation. The method successfully measured vanillin in adult and infant milk formula, biscuits, and human plasma samples with high percentage recoveries (95.3-104.6%) and excellent precision (relative SD; ≤3.85%).

Citrus/urea nitrogen-doped carbon quantum dots as nanosensors for vanillin determination in infant formula and food products via factorial experimental design fluorimetry and smartphone.

Vanillin is a flavouring agent that is prohibited for use in infant food products with ages lower than 6 months. Excessive vanillin usage could lead to eating disorders, nausea, headache, and vomiting. Therefore, it is essential to control the contents of vanillin in food samples, especially in infant formula. Here, we developed a highly sensitive nanosensor for vanillin based on using green synthesized highly fluorescent (QY = 29.5%) N-doped carbon quantum dots (N-CQDs) as a turn-off fluorescent nanoprobe. The N-doped CQDs synthesis was adopted using citrus bulb squeeze extract and the commonly used fertilizer, urea, as substrates. After mixing with vanillin, the fluorescence of the N-CQDs was largely quenched in a vanillin concentration-dependent manner. The sensing conditions were optimized by quality-by-design using a two-level full factorial design (22 FFD). The N-doped CQDs could detect vanillin in the range 0.1-12.0 µg/ml with a limit of detection of 0.013 µg/ml. Next, a smartphone imaging-based assay combined with a UV chamber was adopted and applied for vanillin determination. This simple detection technique showed sensitivity similar to that of the conventional fluorimetric method. Both conventional and smartphone-based methods were successfully applied for the determination of vanillin in infant milk formula and biscuits and could detect real vanillin concentrations in the analyzed samples with high % recoveries (94.5% to 105.5%). At last, the biocompatibility of the newly synthesized N-CQDs was tested, and it was found to be an excellent candidate for cancer cell imaging.

A highly sensitive micelle-enhanced synchronous spectrofluorimetric determination of the recently approved co-formulated drugs, bilastine and montelukast in pharmaceuticals and human plasma at nanogram levels.

In this study, the simultaneous determination of bilastine and montelukast, two recently approved co-formulated antihistaminic medications, was accomplished using a quick, sensitive, environmentally friendly, and reasonably priced synchronous fluorescence spectroscopic approach for the first time. Enhancement of the method's sensitivity down to nanogram levels was achieved by the addition of sodium dodecyl sulfate (1.0% w/v) as a micellar system. According to the results, bilastine and montelukast's fluorescence was measured at 255.3 and 355.3 nm, respectively, using Δλ of 40.0 nm and distilled water as a green diluting solvent. With respect to the concentration ranges of bilastine (5.0-300.0 ng/ml) and montelukast (50.0-1000.0 ng/ml), the method showed excellent linearity (r ≥ 0.9998). The results showed that the suggested method is highly sensitive, with detection limits of 1.42 and 13.74 ng/ml for bilastine and montelukast, respectively. Within-run precisions (intra- and interday) per cent relative standard deviations (RSD) for both analytes were <0.59%. With high percentage recoveries and low percentage RSD values, the designed approach was successfully applied for the simultaneous estimation of the cited medications in their dosage form and human plasma samples. To evaluate the green profile of the suggested method, an analytical GREENNESS metric approach (AGREE) and green analytical procedure index (GAPI) metric tools were used. These two methods for evaluating greenness confirmed that the developed method met the highest number of green requirements, recommending its use as a green substitute for the routine analysis of the studied drugs. The proposed approach was validated according to ICHQ2 (R1) guidelines.

Validated spectrofluorimetric method for the determination of netilmicin based on its interaction with o-phthalaldehyde/mercaptoethanol: Evaluation of the method's greenness.

In this study, netilmicin (NTM) was selectively assessed in its dosage forms after a facile derivatization reaction. The proposed approach was based on the interaction between NTM and o-phthalaldehyde/2-mercaptoethanol (Roth's reagent). The reaction product was fluorometrically measured at λemission of 434 nm after λexcitation of 338 nm. All reaction conditions for achieving the optimum fluorescence switch-on activity were visualized and monitored. Moreover, the method was validated under ICH guidelines, and was linear over the range 30-210 ng/ml after plotting netilmicin concentrations against the corresponding fluorescence intensity values. In addition, the selectivity of the developed method was investigated against either the co-formulated drug (dexamethasone) or a common ophthalmic drop excipient (benzalkonium chloride) without interference from either of them. Furthermore, the developed method was applied to assay netilmicin in various samples of pharmaceutical eye drops with good recovery. Finally, multicriteria greenness and whiteness metrics were used to evaluate the sustainability, greenness, and whiteness of the approach. The applied tools were the AGREE algorithm, the RGB 12 algorithm, and HEXAGON.

Harnessing Oleanolic Acid and Its Derivatives as Modulators of Metabolic Nuclear Receptors.

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to these NRs modulation, OA showed prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

Validated spectrofluorimetric and resonance Rayleigh scattering methods for determining naftidrofuryl in varied pharmaceutical samples based on its interaction with erythrosin B.

Naftidrofuryl is a vasodilator medication used for treating cerebral and peripheral vascular diseases. In this study, two spectroscopical techniques, spectrofluorimetric and resonance Rayleigh scattering (RRS), were utilized to quantify naftidrofuryl in its pharmaceutical samples. The developed methodologies in this study rely on a facile process of forming an association complex between erythrosine B reagent and naftidrofuryl under acidic conditions. The fluorimetric assay is based on the ability of naftidrofuryl to quench and decrease the native fluorescence intensity of the reagent when measured at λ emis . = 550 nm ( λ excit . = 526 nm). Under similar reaction conditions, the RRS method relies on the observed amplification in the RRS spectrum of the reagent at a wavelength of 577 nm following its interaction with naftidrofuryl. The methods exhibited linearity within the ranges 0.2-1.6 µg/ml (r2  = 0.999) and 0.1-1.4 µg/ml (r2  = 0.9994), with limit of quantitation values of 0.146 and 0.099 µg/ml, and limit of detection values of 0.048 and 0.032 µg/ml, for the fluorometric and the RRS methods, respectively. Moreover, the quenching between the dye and naftidrofuryl was studied using Stern-Volmer analysis, and the methodologies were experimentally optimized and validated. Additionally, acceptable recoveries were achieved when the procedures were applied to determine naftidrofuryl in pharmaceutical samples.

Application of quality-by-design for adopting an environmentally green fluorogenic determination of benoxinate hydrochloride in eye drops and artificial aqueous humour.

Herein, a sensitive and selective spectrofluorimetric method has been developed for the determination of the ocular local anesthetic benoxinate hydrochloride (BEN-HCl) in eye drops and artificial aqueous humour. The proposed method is based on the interaction of fluorescamine with the primary amino group of BEN-HCl at room temperature. Following the excitation of the reaction product at 393 nm, the emitted relative fluorescence intensity (RFI) was measured at 483 nm. The key experimental parameters were carefully examined and optimized by adopting an analytical quality-by-design approach. The method used a two-level full factorial design (24 FFD) to obtain the optimum RFI of the reaction product. The calibration curve was linear at the range of 0.10-1.0 µg/mL of BEN-HCl with sensitivity down to 0.015 µg/mL. The method was applied for analyzing the BEN-HCl eye drops and could also assess its spiked levels in artificial aqueous humour with high % recoveries (98.74-101.37%) and low SD values (≤ 1.11). To investigate the green profile of the proposed method, a greenness assessment was performed with the aid of the Analytical Eco-Scale Assessment (ESA) and GAPI. The developed method obtained a very high ESA rating score in addition to being sensitive, affordable, and environmentally sustainable. The proposed method was validated according to ICH guidelines.

Development of Sٍٍensitive Spectrofluorimetric Methods for Determining Netilmicin Based on Selective Condensation Reactions of its Amine Moiety with each Acetylacetone/Formaldehyde and Ninhydrin/Phenylacetaldehyde Reagents.

Netilmicin is an aminoglycoside antibiotic used to treat infections caused by a broad spectrum of Gram-negative and Gram-positive bacteria and is pharmaceutically formulated in ophthalmic dosage forms. In this study, two spectrofluorimetric approaches were designed and developed to switch-on the fluorescence activity of NTC. The first method, or Hantzsch (HNZ) method, was relied on measuring the generated fluorescence intensity upon the condensation of NTC with acetylacetone and formaldehyde (Hantzsch reaction) at λemis=483 nm/λexcit=425.5 nm. While the second fluorometric method (NHD method) was relied on measuring the generated fluorescence intensity upon the condensation of NTC with ninhydrin/phenylacetaldehyde at λemis=482.2 nm/λexcit=385.8 nm. The reaction conditions for the two approaches were well investigated and optimized. The selectivity study for the methods was investigated by determining NTC in the presence of the co-formulated drug (dexamethasone) and pharmaceutical excipients. The validation for two approaches was performed based on ICH guidelines, and ranges of linearity were 0.1-1.2 and 1.5-6.0 µg/mL, while LOD values were 0.039 and 0.207 µg/mL for the HNZ method and the NHD method, respectively. Finally, NTC has been determined in different ophthalmic preparations by the proposed approaches with adequate recovery values.

A new application of isoindole fluorophore derivative in sitagliptin antidiabetic medication assay: Application to dosage forms and biological fluid evaluation.

Dipeptidyl peptidase-4 enzyme suppressant is a unique category of oral antidiabetic medication. Sitagliptin (STG) is a perfect member of this category and is pharmaceutically marketed alone or in combination with metformin. Here, the ideal application of an isoindole derivative for STG assay was developed using a feasible, easy-to-use, economic, and affordable method. STG as an amino group donor can form a luminescent derivative: isoindole on interaction with o-phthalaldehyde and the existence of (2-mercaptoethanol) 0.02% (v/v) as a thiol group donor. Excitation (339.7 nm) and emission (434.6 nm) wavelengths were used to monitor the isoindole fluorophore yield; moreover, each experimental variable was carefully investigated and adjusted. The calibration graph was constructed by plotting fluorescence intensities against STG concentrations, and controlled linearity was observed at concentrations ranging from 50 to 1000 ng/ml. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines were analyzed in depth to prove the technique validation. The implementation of the present technique was extended successfully to the evaluation of various types of STG dose forms and spiking samples of human plasma and urine. The developed technique was shown to be an effective, simple, and quick replacement for quality control and clinical study evaluation of STG.

Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment.

Breast cancer is the second most common cancer in women worldwide. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. Therefore, the localized delivery of chemotherapy helps to overcome such a problem. In this article, self-assembling hydrogels were constructed via inclusion complexation between host ß-cyclodextrin polymers (8armPEG20k-CD and pß-CD) and the guest polymers 8-armed poly(ethylene glycol) capped either with cholesterol (8armPEG20k-chol) or adamantane (8armPEG20k-Ad) and were loaded with 5-fluorouracil (5-FU) and methotrexate (MTX). The prepared hydrogels were characterized by SEM and rheological behaviors. The in vitro release of 5-FU and MTX was studied. The cytotoxicity of our modified systems was investigated against breast tumor cells (MCF-7) using an MTT assay. Additionally, the histopathological changes in breast tissues were monitored before and after their intratumor injection. The results of rheological characterization indicated the viscoelastic behavior in all cases except for 8armPEG-Ad. In vitro release results showed a variable range of release profiles from 6 to 21 days, depending on the hydrogel composition. MTT findings indicated the inhibition ability of our systems against the viability of cancer cells depending on the kind and concentration of the hydrogel and the incubation period. Moreover, the results of histopathology showed the improvement of cancer manifestation (swelling and inflammation) after intratumor injection of loaded hydrogel systems. In conclusion, the obtained results indicated the applicability of the modified hydrogels as injectable vehicles for both loading and controlled release of anticancer therapies.