Design, Characterization and Biopharmaceutical Applications of Novel Green Boron-Carbon Quantum Dots for Quantification of Apalutamide; Greenness Evaluations.

The diagnosis of prostate cancer has been evolving in the current decade, with expected mortality rates of 499,000 death by the year 2030. Apalutamide (APL) has been approved in 2018 as the first drug for the controlling of prostate cancer. APL significant success warrantied its high global sales, which are expected to surpass 58% of segment market sales (together with another drug; enzalutamide). Therefore, new, fast and environmentally friendly analytical methods are required for its determination for the quality control and biological monitoring purposes. The proposed research designs and evaluates the first fluorimetric approach based on novel porous green boron-doped carbon quantum dots (B@CDs) for the determination of APL in biopharmaceutical matrices. The synthetic approach has high quantum yield (31.15%). B@CDs were characterized using several tools, including transmission electron microscopy (TEM), dynamic light scattering (DLS), FTIR and Energy dispersive X-ray spectroscopy (EDX) which proved their improved surface properties with an average nano-diameter of 3.0 nm. The interaction between B@CDs and APL led to enhancement their fluorescence at 441 nm (excitation at 372 nm). The approach was validated for the determination of APL within concentration range of 15.0-700.0 ng mL- 1 with quantification limit LOQ 4.37 ng mL- 1 and detection limit LOD 1.44 ng mL- 1. The approach was successfully applied for the determination of APL in human plasma and pharmaceutical monitoring of its marketed tablet form. Then, the approach was assessed for its environmental impact using different metrics and proved its ecological greenness.

Synthesis of organic solvent-free nitrogen-doped carbon quantum dots as unique green fluorimetric probes for analysis of abrocitinib in human plasma.

Atopic dermatitis (AD) is a persistent, inflammatory skin condition that impacts approximately 15 to 20% of children and 1 to 3% of adults globally. Common skin manifestations include papules, papulovesicular, and brown or red patches with swelling, crusting, and flaking. Therefore, the drug abrocitinib (ABR) was approved by the US FDA as an oral treatment for atopic dermatitis. The present study outlines the development of innovative, thermostable, and pH-stable organic solvent-free nitrogen-doped carbon dots (N@CQDs) synthesized through a one-step method for evaluating ABR with a notable quantum yield of 33.84% to minimize the use of organic solvents. Their cost-effectiveness, eco-friendly characteristics, and outstanding photocatalytic properties have established them as a promising alternative to conventional luminescent techniques like fluorescent dyes and luminous derivatization technique. The reaction of ABR with N@CQDs led to a significant decrease in the luminescent response of the produced green and stable carbon quantum dots at 513 nm. The detection range was determined to be 1.0-150.0 ng mL-1, with a lower limit of quantitation (LOQ) equal to 0.52 ng mL-1 based on the linear graph. The green method effectively used for analysis of ABR in pharmaceutical tablets and pharmacokinetic study with high sensitivity.

Rapid One-Pot Microwave Assisted Green Synthesis Nitrogen Doped Carbon Quantum Dots as Fluorescent Precursor for Estimation of Modafinil as Post-Covid Neurological Drug in Human Plasma with Greenness Assessments.

The neuro-stimulant anti-narcoleptic drug as modafinil (MOD) is used to treatment neurological conditions caused by COVID-19. MOD was used to treatment narcolepsy, shift-work sleep disorder, and obstructive sleep apnea-related sleepiness. So, an innovative, quick, economical, selective, and ecologically friendly procedure was carried out. A highly sensitive N@CQDs technique was created from green Eruca sativa leaves in about 4 min using microwave synthesis at 700 w. The quantum yield of the synthesized N@CQDs was found to be 41.39%. By increasing the concentration of MOD, the quantum dots' fluorescence intensity was gradually quenched. After being excited at 445 nm, the fluorescence reading was recorded at 515 nm. The linear range was found to be in the range 50 - 700 ng mL-1 with lower limit of quantitation (LOQ) equal to 45.00 ng mL-1. The current method was fully validated and bio analytically according to (US-FDA and ICH) guidelines. Full characterization of the N@CQDs has been conducted by high resolution transmission electron microscope (HRTEM), Zeta potential measurement, fluorescence, UV-VIS, and FTIR spectroscopy. Various experimental variables including pH, QDs concentration and the reaction time were optimized. The proposed study is simply implemented for the therapeutic drug monitoring system (TDMS) and various clinical laboratories for further pharmacokinetic research.

Development of cysteine-doped MnO2 quantum dots for spectrofluorimetric estimation of copper: applications in different matrices.

Copper (Cu) plays a role in maintaining healthy nerve cells and the immune system. Osteoporosis is a high-risk factor for Cu deficiency. In the proposed research, unique green, fluorescent cysteine-doped MnO2 quantum dots (Cys@MnO2 QDs) were synthesized and assessed for the determination of Cu in different food and hair samples. The developed quantum dots were synthesized with the help of cysteine using a straightforward ultrasonic approach to create 3D fluorescent Cys@MnO2 QDs. The resulting QDs' morphological and optical characteristics were carefully characterized. By adding Cu ions, the intensity of fluorescence for the produced Cys@MnO2 QDs was found to be dramatically reduced. Additionally, the applicability of Cys@MnO2 QDs as a new luminous nanoprobe was found to be strengthened by the quenching effect grounded on the Cu-S bonding. The concentrations of Cu2+ ions were estimated within the range of 0.06 to 7.00 µg mL-1, with limit of quantitation equal to 33.33 ng mL-1 and detection limit equal to 10.97 ng mL-1. The Cys@MnO2 QD technique was applied successfully for the quantification of Cu in a variety of foods, including chicken meat, turkey, and tinned fish, as well as in human hair samples. The chance that this novel technique could be a useful tool for figuring out the amount of cysteine in bio-samples is increased by the sensing system's remarkable advantages, which include being rapid, simple, and economical.

Ultrasensitive green spectrofluorimetric approach for quantification of Hg(II) in environmental samples (water and fish samples) using cysteine@MnO2 dots.

Mercury (Hg2+ ) is a natural element present in foods such as fish, water and soil. Exposure to mercury leads to severe toxic effects on the nervous, digestive, and immune systems. Here, a novel, green, and environmentally friendly fluorescent probe decorated with cysteine/MnO2 quantum dots (Cys@MnO2 QDs) was synthesized. This synthesis was carried out using a simple ultrasound technique with the aid of cysteine for fabricating Cys@MnO2 QDs to estimate Hg levels in fish and water samples. In this morphological study, Cys@MnO2 QDs were fully characterized using high-resolution transmission electron microscopy, zeta potential analysis, fluorescence, ultraviolet-visible and infrared spectroscopy. The fluorescence of the synthesized Cys@MnO2 QDs was significantly quenched by gradually increasing the Hg(II) concentration. The quenching mechanism based on the Hg-S bonds strengthened the utility of the Cys@MnO2 QDs as a novel luminescent nanoprobe. The estimation of Hg was linear in the concentration range 0.7-100.0 ng mL-1 with a limit of quantitation equal to 0.30 ng mL-1 . The Cys@MnO2 QDs are fluorescent probes with various benefits such as speed, ease of use, cost- effective, and being environmentally friendly; they are easily applied in food manufacturing and for public health improvement.

Applicability of fluorescamine as a fluorogenic reagent for highly sensitive fluorimetric analysis of the tyrosine kinase inhibitor (avapritinib) in pharmaceuticals and biological samples.

Avapritinib (AVP) was the first precision drug to be approved by the US Food and Drug Administration (FDA) in 2020 for patients suffering from metastatic gastrointestinal stromal tumors (GISTs) and progressive systemic mastocytosis. The analysis of AVP in pharmaceutical tablets and human plasma was then carried out using a fast, efficient, sensitive, and simple fluorimetric method using a fluorescamine reagent. The procedure is based on the interaction between fluorescamine as a fluorogenic reagent and the primary aliphatic amine moiety in AVP using borate buffer solution at pH 8.8. The produced fluorescence was measured at 465 nm (Excitation at 395 nm). The calibration graph's linearity range was discovered to be 45.00-500.0 ng mL-1 . Utilizing the International Council for Harmonization (ICH) and US-FDA recommendations, the research technique was validated and bioanalytically validated. The proposed approach was effectively employed for determining the stated pharmaceuticals in plasma with a high percentage of recovery ranging from 96.87 to 98.09 and pharmaceutical formulations with a percentage of recovery equal to 102.11% ± 1.05%. In addition, the study was extended to a pharmacokinetic study of AVP with 20 human volunteers as a step for AVP management in therapeutic cancer centers.

An eco-friendly matrix-augmented fluorescence spectroscopic approach for the analysis of mitoxantrone, an oncogenic therapy; application to the dosage form and biological matrices.

Mitoxantrone (MXN) is a synthetic anthracenedione oncogenic therapy. It is often prescribed as an anticancer agent to manage a variety of cancers. A green, fast, and easy fluorimetric technique for the assay of MXN as a topoisomerase type II enzyme suppressor. An investigation of MXN's fluorescence behavior in various media and solvents constituted the basis for this new technique. Methanol was shown to enhance the intrinsic fluorescence considerably. After excitation at 610 nm, the highest fluorescence intensity was found at 675 nm. Various experimental parameters, such as media, solvents, and pH levels, were tested and adjusted. ICH (International Conference on Harmonization) guidelines were followed when validating procedures. It was possible to achieve linearity in the 0.02-1.50 µg ml-1 with the method. The sensitivity (in terms of limit of detection and limit of quantification) was 0.003 and 0.008 µg ml-1 , indicating low toxicity. As a result, the current technology has a remarkable recovery for detecting residues in diverse bodily fluids. Also, the quantum yield was estimated for the designed system. Finally, the method was rated by eco-scale scoring.

Ultra-Sensitive Fluorimetric Method for the First Estimation of Vonoprazan in Real Human Plasma and Content Uniformity Test.

Vonoprazan (VON) has been approved recently via US-FDA in 2015 as the first in class of potassium competitive acid blocker group. VON is used for management of GIT ulcer, reflux esophagitis and for eradication of Helicobacter pylori. So, the first spectrofluorimetric method was developed for estimation of VON in real human plasma and content uniformity test. The fluorimetric methodology based on reaction of secondary amine group in VON with benzofurazan (0.05% w/v NBD-Cl) reagent as nucleophilic substitution reaction in alkaline medium (0.1 M borate buffer pH 8.2) to produce highly fluorescent product measure at 530 nm after excitation at 465 nm. The linear calibration range was found 15 to 200 ng mL-1 with lower limit of quantitation (LOQ) equal to 8.57 ng mL-1. The method was successfully applied for estimation of VON in pharmacokinetic (PK) and content uniformity studies. The maximum plasma concentration was found to be (Cmax) 71.03 ng mL-1 after maximum time (tmax) equal to 1.5 ± 0.15 h. The presented strategy also applied to ensure concentration of drug in each tablet using content uniformity test with high percent of recovery 100.05 ± 0.66. The proposed method was established for clinical laboratories and therapeutic drug monitoring studies.

Resonance Rayleigh scattering approach based on association complex formation with erythrosine B for determination of venlafaxine, application to the dosage form and spiked human plasma.

The interaction of venlafaxine hydrochloride (VLX) with erythrosine B was investigated using a resonance Rayleigh scattering (RRS) spectroscopic technique. In acetate buffer (pH 3.4), erythrosine B reacted with VLX to form a 1:1 ion-pair complex with concomitant enhancement in RRS intensity that was measured at 330 nm. In addition, the stability constant and the change in free energy of the reaction were estimated. Based on this interaction a new method was developed for a sensitive VLX analysis using erythrosine B as a probe. The results indicated that this method had good selectivity in the presence of coexisting compounds. The scattering intensity (ΔIRRS ) was linearly dependent on VLX concentration over the range 0.04-1.0 µg ml-1 with a determination coefficient (r) of 0.9998. The limit of detection and limit of quantitation were 0.01 and 0.03 µg ml-1 , respectively. This method could be suitably used for analysis of VLX in pharmaceutical capsules and human plasma.

Quantification of tyramine in different types of food using novel green synthesis of ficus carica quantum dots as fluorescent probe.

Tyramine (TYM) is catecholamine releasing compound and TYM rich food causes hypertensive crisis due to a combination with monoamine oxidase inhibitor (MAOIs). Therefore, analysis of TYM in TYM rich food as (old cheese, cured meat, sausage, pickled olive and canned fish) and the environment is essential for hypertensive patients and to improvement of food industries. In this work, TYM was analyzed in different types of food using novel green synthesis carbon dots from Ficus carica (fig fruits). The gradual addition of TYM to polyamine carbon quantum dots (PA@CQDs) led to enhancement of the quantum dots fluorescence due to formation of hydrogen bonding between quantum dots and TYM. The calibration graph was plotted in the range 5-400 ng mL-1 . The method was applied for the determination of TYM in different types of food as old cheese, cured meat, sausage, pickled olive and canned fish. The lower limit of quantitation (LOQ) was found to be 1.68 ng mL-1 . The method was successfully applied for the quantification of TYM in varying types of food with high sensitivity and high economic effect due to the reusability of the quantum dots. The optical and morphological characters of quantum dots were studied carefully.

Development of dual function polyamine-functionalized carbon dots derived from one step green synthesis for quantitation of Cu2+ and S2- ions in complicated matrices with high selectivity.

The study of biologically important Cu2+ and S2- ions has drawn great attention in the recent years since an abnormal level of these ions is an indication for health impairment. Therefore, a reliable strategy for effective fluorescence determination of Cu2+ and S2- ions was developed. Simply, the method based on economical plant-dependent thermolysis procedure for efficient green synthesis of water dispersible luminescent polyamine-based carbon dots (PA@C-dots) utilizes Vitis vinifera juice as precursor with a high quantum yield (32.1%) and good photo-stability. The fluorescent PA@C-dots were characterized by different spectroscopical, physical, and structural techniques. Furthermore, the synthesized PA@C-dots can be used as an efficient dual functional fluorescent probe for the sensitive and selective estimation of Cu2+ and S2- ions. The incorporation of Cu2+ ions and their adsorption on the surface of PA@C-dot skeleton leads to the respectable fluorescence quenching of C-dots (turn-off mode). The Cu2+-PA@C-dot was found to be sensitive to S2- ions. The addition of S2- recovers the fluorescence (turn-on mode) of Cu2+-PA@C-dots, thanks to its capacity for withdrawing Cu2+ from the shell of PA@C-dots. Fluorescence quenching in the range of 0.07-60 µM Cu2+ was obtained with LOD and LOQ of 0.02 and 0.066 µM, respectively. Sulfide detection provides linearity in the range of 0.8 to 95 µM with LOD and LOQ of 0.24 and 0.79 µM, respectively. The optimal excitation and emission wavelengths for all experiments are 435 nm and 498 nm, respectively. Experiment results elucidate that the proposed method is suitable for Cu2+and S2- ion detection in environmental water samples. Graphical abstract Green synthesis of polyamine-functionalized nanoprobe by thermolysis method from plant source as bifunctional sensing platform for determination of Cu2+ and S2- in environmental water samples.

Colorimetric and fluorimetric (dual-mode) nanoprobe for the determination of pyrogallol based on the complexation with copper(II)- and nitrogen-doped carbon dots.

Carbon dots doped with copper(II) and nitrogen (Cu,N@C-dots) were prepared and are shown to be viable fluorescent nanoprobe for pyrogallol (PGL) was developed for the first time. The reaction is based on (a) the complexation reaction between Cu,N@C-dots and catechol moiety, and (b) the generation of a quinone-like structure. Thus, the co-ordination complex formed between Cu(II) in C-dots and PGL results in quenching of the fluorescence of C-dots. In addition, the formation of a yellow color due to complex formation between the nanoprobe and Cu(II) allowed the colorimetric determination of PGL. The nanoprobe was prepared by thermal synthesis, using ethylenediaminetetraacetic acid salt and copper(II) chloride as sources for carbon, nitrogen and copper, respectively. The carbon dots were characterized by UV-VIS spectroscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, transmission electron microscopy) and dynamic light scattering. Fluorescence drops linearly in the 0.15 to 70 µM PGL concentration range with a detection limit of 39 nM and a relative standard deviation of 1.8%. The optimal excitation and emission wavelengths are 370 nm and 428 nm, respectively. The colorimetric assay has a linear response at 325 nm absorption wavelengths in the 6 to 140 µM PGL concentration range with a detection limit of 1.8 µM and a 2.3% relative standard deviation. Graphical abstractDual mode colorimetric and fluorimetric nanoprobe was designated for pyrolgallol determination based on complexation with copper(II)- and nitrogen-doped carbon dots.

A Customizable Quantum-Dot Cellular Automata Building Block for the Synthesis of Classical and Reversible Circuits.

Quantum-dot cellular automata (QCA) are nanoscale digital logic constructs that use electrons in arrays of quantum dots to carry out binary operations. In this paper, a basic building block for QCA will be proposed. The proposed basic building block can be customized to implement classical gates, such as XOR and XNOR gates, and reversible gates, such as CNOT and Toffoli gates, with less cell count and/or better latency than other proposed designs.

Semantic Clustering of Search Engine Results.

This paper presents a novel approach for search engine results clustering that relies on the semantics of the retrieved documents rather than the terms in those documents. The proposed approach takes into consideration both lexical and semantics similarities among documents and applies activation spreading technique in order to generate semantically meaningful clusters. This approach allows documents that are semantically similar to be clustered together rather than clustering documents based on similar terms. A prototype is implemented and several experiments are conducted to test the prospered solution. The result of the experiment confirmed that the proposed solution achieves remarkable results in terms of precision.

Design of new boron-doped carbon dots for nano-level assay of nebivolol in human plasma and commercial products; Application to greenness assessments.

Recently, nanomaterials have attracted a lot of attention due to their potential as effective fluorescent nano-sensor probes. They were distinguishing substitutes for other luminescent techniques, such as fluorescent dyes and luminous derivatization, because of their affordability, environmental friendliness, and special photocatalytic properties. In the suggested work, a straightforward method was used to create boron and nitrogen carbon dots (B@CDs) with a good quantum yield value of 31.15 % utilizing boric acid and di-sodium EDTA. For the purpose of characterizing QDs, a variety of instruments were employed, such as transmission electron microscopy, fluorescence spectroscopy, X-ray FTIR, and UV-VIS spectroscopy. Nebivolol (NEB) is a cardiovascular medication used globally to treat congestive heart failure and hypertension, is in the meantime. For this reason, a brand-new, environmentally friendly analytical technique was created to determine the amount of human plasma, uniformity test, and commercial nebivolol (NEB) tablets. After gradually adding NEB, the response of B@CQDs was enhanced at 438 nm (excitation at 371 nm). The calibration graph ranged between 20 and 500 ng mL-1 with a quantification limit (LOQ) of 2.50 ng mL-1 and a detection limit (LOD) of 0.82 ng mL-1.

Design, Characterization, and Bioanalytical Applications of Green Terbium- and Nitrogen-Doped Carbon Quantum Dots as a Fluorescent Nanoprobe for Omadacycline Analysis.

Terbium- and nitrogen-doped carbon quantum dots (Tb,N@CQDs) were greenly created employing microwave synthesis from plum juice with terbium nitrate. The synthesis of Tb,N@CQDs was fast (7 min) with a high quantum yield (35.44%). Tb,N@CQDs were fully characterized using transmission electron microscopy, Zeta potential analysis, fluorescence, and ultraviolet spectroscopy. Omadacycline (OMC) is a broad-spectrum tetracycline that has been recently approved by the United States Food and Drug Act (FDA) in October 2018. OMC is the first oral aminomethylcycline class antibiotic drug that was authorized for the treatment of acute skin structure infections and community-acquired pneumonia. Tb,N@CQDs exhibited emission at 440 nm after excitation at 360 nm, where their fluorescence intensity showed a reduction upon addition of OMC. The experimental parameters were further studied and optimized. The linear range was between 40 and 60 parts per billion (ppb), with (limit of quantitation) equal to 34.78 ppb. The proposed approach was validated for bioanalytical purposes using FDA guidelines and proved to be straightforward, cheap, highly sensitive, and very selective, which can be used in clinical studies. The developed approach proved to be green using some current assessment metrics and was applied successfully for the determination of OMC in human plasma, milk, and pharmaceutical formulations as well as pharmacokinetic study.

A new green fluorimetric micelle complexation approach for reduction of the consumed solvent and quantification of avapritinib in biological fluids.

Avapritinib (AVA) is the first medication authorized by the US-FDA in 2020 for the management of gastrointestinal stromal tumours (GISTs) that can't be treated by surgery. Cancer is among the most common causes of death worldwide and is the second most common cause of death after cardiovascular disease. Therefore, a quick, easy, sensitive, and straightforward fluorimetric approach was used to analyse AVA in pharmaceutical materials and blood plasma (pharmacokinetic). The suggested technique relies on 2% sodium dodecyl sulphate (SDS, pH 4) micellar system augmentation of the fluorescence of the tested drug. The technique demonstrated high relative fluorescence intensity (RFI) at 430 nm after excitation at 340 nm. Concentrations ranging from 20.0-400.0 ng mL-1 with a limit of quantitation of 9.47 ng mL-1 were used to obtain luminescence data for the studied medicine. In addition, the quantum yield of the AVA fluorescence was increased with the gradual addition of a surfactant at a concentration above its critical micellar level. This knowledge has been exploited to enhance the effectiveness of a spectrofluorometric technique for the estimation of AVA in human plasma (98.95 ± 1.22%) and uniformity tests with greenness assessments. The conditions for enhanced fluorescence were optimized and fully validated using US-FDA and International Conference on Harmonization (ICH) rules. This innovative strategy was expanded for AVA stability research in human plasma across various circumstances. This approach is an eco-friendly solution compared to traditional testing methods that use hazardous chemicals.

Facile decoration of one-pot fluorescence probe-patterned reaction for sensing and ultrasensitive determination of tradjenta, a new type 2 diabetes oral therapy.

Type 2 diabetes can be cured by using tradjenta (also known as Linagliptin), a new therapeutic drug that is an inhibitor of the dipeptidyl peptidase-4 enzyme. Tradjenta is administered orally alone or in combination with metiguanide or empagliflozin. An easy and specific fluorimetric analysis of Tradjenta was developed and demonstrated in the present investigation. The Hantzsch reaction method, which generates a fluorescent dihydropyridine derivative, is the basis of this assay. In a Toerell-Stenhagen buffered solution, the unsubstituted amine group of Tradjenta interacted with 2,4-Pentadione/Oxomethane. Spectrofluorimetry was utilized for this investigation at an excitation/emission wavelength of 421/480 nm. When comparing the Tradjenta concentration to the tracked fluorimetric signal, the method revealed linearity over the concentration range of 0.05 to 1.2 µg/mL. By strictly altering system parameters and analyzing the validation factors following International Council for Harmonisation (ICH) requirements, the outcomes were achieved. Finally, the proposed approach was successfully applied to assay the drug not only in its raw form and prescribed formulations but also to evaluate the tablet's uniformity of content.

Feasible spectrofluorimetric approach for the ultrasensitive determination of lomefloxacin based on synergistic effects of micellization and metal complexation.

The purpose of the present work was to establish a fast and convenient strategy for lomefloxacin analysis using a fluorimetric approach. The methodology was based on the complex formation of the drug with aluminum ion to give a product having high fluorescence. Adding sodium dodecyl sulfate led to further boosting the intensity of fluorescence which was recorded at 429 nm after excitation at 332 nm. The relationship of emission intensity with lomefloxacin concentration was linear at 10-130 ng mL-1 with a correlation coefficient of 0.9996. The quantitation limit was 11.4 ng mL-1 and detection limit was 3.8 ng mL-1. The reaction conditions were carefully studied which included the pH, buffer type, its concentration, the type and concentration of surfactant and the diluting solvent. The method was utilized to quantify the aforementioned drug in tablet formulations and in real human plasma with high accuracy and reliability.