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.

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.

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.

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.

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.

Ultra-sensitive and selective fluorescence approach for estimation of elagolix in real human plasma and content uniformity using boron-doped carbon quantum dots.

Elagolix (ELX) is an orally administered non-peptidic GnRH antagonist that has been approved by the Food and Drug Administration in 2018 for the treatment of endometriosis pain. A sensitive and selective method for estimating elagolix (ELX) in human plasma and content uniformity was developed and validated. The spectrofluorimetric technique was used to investigate ELX utilizing boron-doped carbon quantum dots (B@CQDs). After gradually adding ELX, the quantum dots fluorescence was enhanced with LOQ of 1.74 ng mL-1, the calibration curve between ELX and corresponding fluorescence intensity was found over a range of 4-100 ng mL-1. The method was successfully applied in real human plasma with pharmacokinetic study and content uniformity test. The pharmacokinetic parameters as Cmax were found to be 570 ± 5.32 ng. mL-1 after 1 h, t1/2 was found to be 6.50 h, and AUC was found to be 1290 ± 30.33 ng. h. mL-1. B@CQDs were characterized using variety of instruments. The strategy is simple to implement in clinical labs and therapeutic drug monitoring systems.

Colorimetric and fluorometric nanoprobe for selective and sensitive recognition of hazardous colorant indigo carmine in beverages based on ion pairing with nitrogen doped carbon dots.

Indigo carmine (IC) dye is hazardous and allergenic for humans even though it has been excessively used in a wide range of industries. Therefore, the quantitative determination of IC is still challenging. Herein, for the first time, we have developed fluorometric and colorimetric dual-mode nanoprobe derived from the ion-pair association complex between the negatively charged IC and positively charged N@C-dots in pH = 3.0. Consequently, the binding between N@C-dots and IC resulted in cyan blue and quenching of N@C-dots fluorescence. The dependence of the fluorescence response on IC concentrations was linear over the range of 0.73-10.0 µM (R2 = 0.9989) with LOD of 0.24 µM. On the other hand, the linearity of the colorimetric method ranged from 9.97 to 80.0 µM (R2 = 0.9986) with LOD of 3.3 µM. The sensor was applied for estimation of IC in fruit juice and soft drink without the need for exhaustive extraction steps.

A rapid FTIR spectroscopic assay for quantitative determination of Memantine hydrochloride and Amisulpride in human plasma and pharmaceutical formulations.

A selective, new, rapid and nondestructive Fourier transform Infrared spectroscopic assay has been developed for simultaneous determination of Memantine hydrochloride and Amisulpride in human plasma and their pharmaceutical formulations without interference from common dugs excipients. A binary mixture of ME and nonselective ß-blocker namely; carvidalol has been determined the solid-state by FTIR spectroscopy for the first time. The linear range had been extent from 1.0 to 8.0 and 1.0 to 10.0 µg/mg, for ME and AMS respectively. The detection limits were 0.29 and 0.23 µg/mg while quantitation limits were 0.90 and 0.71 µg/mg for ME and AMS respectively. The developed assay has been validated according to ICH & USP recommendations and successfully applied for quantitative determination of selected drugs in biological fluid.

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.

One pot fabrication of fluorescein functionalized manganese dioxide for fluorescence "Turn OFF-ON" sensing of hydrogen peroxide in water and cosmetic samples.

In recent decades, H2O2 has been promoted as a health indicator because its moderate to high levels can cause some health problems. Herein, we developed a new fluorescent nanoprobe for rapid, selective and sensitive detection of H2O2. The fluorescent nanoprobe is composed of fluorescein dye (FLS) as a fluorescent probe and MnO2 nanosheets (MnO2 NS) as a quencher. In this study, H2O2 can reduce MnO2 NS in the synthesized composite and release FLS, causing sufficient recovery of fluorescent signal related to the concentration of H2O2. The nanoprobe, with λ ex/λ em at 495/515 nm, has a linear range of 0.04-30 µM, with a limit of detection (LOD) of 7.5 nM and a limit of quantitation (LOQ) of 21 nM. The mean relative standard deviation (RSD) was 2.6% and the applicability of the method was demonstrated by the determination of H2O2 in water and cosmetic samples.

A new spectrofluorimetric assay for quantification of Amisulpride and Memantine hydrochloride in real human plasma sample and pharmaceutical formulations via Hantzsch reaction.

A new, selective and accurate spectrofluorimetric assay has been described for detection of Amisulpride and Memantine hydrochloride in pharmaceutical formulations and real plasma samples. The described assay depends on the reaction between the primary amino group of the selected drugs with acetyl acetone & formaldehyde in an acetate buffer of pH4.8. The derivatized product showed yellow fluorescence at λex=418nm and λem=484.5nm. The calibration graph was linear in the range of 0.05-0.5 and 0.2-1µgmL-1 for AMS and ME, orderly. The limits of detection were 0.0085 and 0.0153µgmL-1, and the limits of quantitation were 0.026 and 0.0464µgmL-1 for AMS and ME respectively. Validation of the described assay was in consonance with ICH guideline. Due to the sensitivity of the prescribed assay, it permits the determination of selected medications in biological sample quantitatively.

Utility of chromogenic property of 2, 2-dihydroxyindane-1, 3-dione for quantification of Memantine hydrochloride in pure, pharmaceutical preparation and application to uniformity testing.

Accurate, simple, sensitive, and fast spectrophotometric assay was applied for the quantification of certain anti-Alzheimer drug namely; Memantine hydrochloride, in its bulk and pharmaceutical preparation. The described assay has been established on the reaction between the primary amino moiety of the cited drug and 2,2-dihydroxyindane-1,3-dione reagent in N,N'-dimethylformamide medium in boiling water bath. Which give Ruhemann's purple color that can be determined at λmax = 595 nm. Beer's law has been obeyed within drug concentration range from 10-120 µg per milliliter. Detection limit and quantitation limit have been 1.6 & 4.9 µg per milliliter respectively. Developed procedure has been validated in agreement with International Conference of Horizon recommendations and applied successfully for detection of cited drug in bulk, pharmaceutical dosage form and content uniformity testing.

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 new sensitive approach for spectrofluorimetric assay of Milnacipran and Amisulpride in real plasma and pharmaceutical preparations via complexation with Eosin Y dye.

An accurate, economic, rapid, reliable spectrofluorimetric assay was developing for the assay of definite anti-depressant drugs namely Amisulpride and Milnacipran hydrochloride, in those pharmaceutical preparation and biological fluid. The suggested method was established on the detection of quenching process resulting from the action of AMS and MCN to the native fluorescent EosinY. A binary complex between selected medications and Eosin Y was established in acetate buffer (0.2 M) at pH 3.3 & 4.0 for AMS and MCN respectively. The relative fluorescence capacity was determined at λex = 301.8 nm and λem = 542.7 nm. The calibration graphs had been linear through extent from 0.02 to 0.3 and 0.1-1 µg mL-1, to both dugs respectively. Detection limits have been 0.0047 & 0.0188 µg mL-1 while quantitation limits have been 0.0141 & 0.0569 µg mL-1 to AMS & MCN respectively. Developed assay has been validated in agreement with ICH recommendations. Due to high sensitivity of the described assay, it allows the quantitation of anti-depressant drugs through biological fluid.

Renal Transplant in Patients With Abnormal Bladder: Impact of Causes on Graft Function and Survival.

OBJECTIVES: Successful kidney transplant depends partly on the normal physiologic functioning of the bladder, which involves effective urine storage and emptying. The bladder may become abnormal owing to various urologic and neuropathic disorders. Patients with abnormal bladders need careful management before and after transplant. In this study, we aimed to determine the outcomes of renal transplants in relation to various causes of abnormal bladder. MATERIALS AND METHODS: We conducted a retrospective review of 25 patients with abnormal bladder who received 30 renal transplants between 1990 and 2014. The patients were divided into neurologic and urologic groups based on the causes of abnormal bladder. Patient demographics, graft function, survival, and postoperative complications were compared. RESULTS: The most common urologic cause was posterior urethral valve (14 patients), while the most common neurologic cause was spina bifida (6 patients). There was no statistically significant difference in graft survival at 1, 3, and 5 years between patients with neurologic and urologic causes of abnormal bladder as well as at long-term follow-up. However, the mean estimated glomerular filtration rate at 1, 3, and 5 years was higher among patients with neurologic causes than in those with urologic causes, although the difference was statistically significant only at 1 year (61 ± 34 vs 37 ± 19 mL/min; P = .025). Stone formation was reported only in patients whose abnormal bladder had neurologic causes, and no incidence was reported in patients with urologic causes (20% vs 0%; P = .038). The incidence of other postoperative complications was not statistically significant between the 2 groups. CONCLUSIONS: With careful evaluation and proper preoperative correction of abnormal bladder dysfunction and optimization of the emptying and storage functions of the bladder, the causes of abnormal bladder did not appear to impact graft function and survival or overall rate of postoperative complications.

A sensitive spectrophotometric method for the determination of H2-receptor antagonists by means of N-bromosuccinimide and p-aminophenol.

A simple, accurate and sensitive spectrophotometric method for determination of H2-receptor antagonists: cimetidine (CIM), famotidine (FAM), nizatidine (NIZ), and ranitidine hydrochloride (RAN) has been fully developed and validated. The method was based on the reaction of these drugs with NBS and subsequent measurement of the excess N-bromosuccinimide by its reaction with p-aminophenol to give a violet colored product (lambda max at 552 nm). Decrease in the absorption intensity (Delta A) of the colored product, due to the presence of the drug, was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under optimal conditions, linear relationships with good correlation coefficients (0.9988-0.9998) were found between Delta A values and the corresponding concentrations of the drugs in a concentration range of 8-30, 6-22, 6-25, and 4-20 microg mL(-1) for CIM, FAM, NIZ, and RAN, respectively. Limits of detection were 1.22, 1.01, 1.08, and 0.74 microg mL(-1) for CIM, FAM, NIZ, and RAN, respectively. The method was validated in terms of accuracy, precision, ruggedness, and robustness; the results were satisfactory. The proposed method was successfully applied to the analysis of the above mentioned drugs in bulk substance and in pharmaceutical dosage forms; percent recoveries ranged from 98.5 +/- 0.9 to 102.4 +/- 0.8% without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.

Spectrophotometric determination of H(2)-receptor antagonists via their oxidation with cerium(IV).

A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of H(2)-receptor antagonists: cimetidine, famotidine, nizatidine and ranitidine hydrochloride. The method was based on the oxidation of these drugs with cerium(IV) in presence of perchloric acid and subsequent measurement of the excess Ce(IV) by its reaction with p-dimethylaminobenzaldehyde to give a red colored product (lambda(max) at 464nm). The decrease in the absorption intensity of the colored product (DeltaA), due to the presence of the drug was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990-0.9994) were found between DeltaA values and the concentrations of the drugs in a concentration range of 1-20microgml(-1). The assay limits of detection and quantitation were 0.18-0.60 and 0.54-1.53microgml(-1), respectively. The method was validated, in terms of accuracy, precision, ruggedness and robustness; the results were satisfactory. The proposed method was successfully applied to the determination of the investigated drugs in pure and pharmaceutical dosage forms (recovery was 98.3-102.6+/-0.57-1.90%) without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.

Sensitive indirect spectrophotometric method for determination of h2-receptor antagonists in pharmaceutical formulations.

A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of H2-receptor antagonists: cimetidine, famotidine, nizatidine, and ranitidine hydrochloride. The method was based on the oxidation of these drugs with cerium (IV) in presence of perchloric acid and subsequent measurement of the excess Ce (IV) by its reaction with p-dimethylaminocinnamaldehyde to give a red colored product (λmax at 464 nm). The decrease in the absorption intensity (ΔA) of the colored product, due to the presence of the drug was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9985-0.9994) were found between ΔA values and the concentrations of the drugs in a concentration range of 1-16 µg ml(-1). The assay limits of detection and quantitation were 0.12-0.44 and 0.37-1.33 µg ml(-1), respectively. The method was validated, in terms of accuracy, precision, ruggedness, and robustness; the results were satisfactory. The proposed method was successfully applied to the analysis of the investigated drugs in their pure and pharmaceutical dosage forms (recovery was 98.8-102.5 ± 0.79-1.72%) without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.