Promoting the sensitive detection of ethamsylate via a colorimetric sensing platform based on the enhanced oxidase-mimicking activity of ultrathin MnO2 nanosheets.

In this work, we present a novel colorimetric sensing platform for the sensitive detection of ethamsylate (ETM) usingultrathin MnO2 nanosheets with enhancedoxidase-mimicking activity. A facile template-free hydrothermal process was applied to synthesize the MnO2 nanosheets under mild conditions. The nanosheets exhibited oxidase-mimicking activity, facilitating the conversion of TMB into the blue-colored oxTMB in the absence of H2O2. However, the presence of ETM inhibited this activity, resulting in the conversion of oxTMB back to colorless TMB and a substantial decrease in the blue color intensity. The colorimetric response exhibited a linear relationship with ETM concentration over the range of 0.5 to 10.0 µg/mL and a detection limit of 0.156 µg/mL. To further elucidate the underlying mechanism, we performed extensive characterization and kinetic experiments. The findings demonstrated that this unique property is attributed to the remarkable capacity of the MnO2 nanosheets to absorb oxygen, producing superoxide radicals (O2-). The oxidase-mimicking activity of the nanosheets was further confirmed by the reaction kinetics, following Michaelis-Menten's behavior. Moreover, the applicability of the sensing platform was assessed by determining ETM concentrations in various real samples (different pharmaceuticals, human plasma, and environmental water). The well-established platform demonstrates the prospective role that nanomaterials-based sensing platforms may play in clinical diagnostics, pharmaceutical analysis, and other relevant fields.

Carbon dots-adorned silver nanoparticles as a straightforward sustainable colorimetric sensor for the rapid detection of ketotifen in eye drops and aqueous humor.

The rapid and accurate detection of drug molecules in pharmaceutical formulations and biological samples is of paramount importance. In this research article, we present a novel colorimetric sensor based on carbon dots decorated silver nanoparticles (CDs/AgNPs) for the rapid detection of ketotifen (KTF), a widely used antihistamine drug. The CDs were synthesized via a facile one-step microwave-assisted method and subsequently conjugated onto AgNPs through a simple adsorption process, forming a stable CDs/AgNPs composite. The resulting composite exhibited unique optical properties, including a strong absorption peak at 410 nm with remarkable intensity reduction and color changes upon the addition of KTF. The developed colorimetric sensor exhibited a wide linear range of 3.0-40.0 µg mL-1 (R2 = 0.9996), with a %RSD of 2.41, and a low limit of detection (LOD) of 0.981 µg mL-1. Furthermore, the sensor's practical applicability was evaluated by successfully detecting KTF in eye drops and artificial aqueous humor, demonstrating a remarkable percentage recovery exceeding 96.0 %. Finally, a comprehensive evaluation of the greenness and blueness of the method was performed using analytical eco-scale, GAPI, AGREEprep, and BAGI tools. The results of these assessments indicate its exceptional sustainability. Overall, the proposed method holds significant potential for applications in pharmaceutical quality control and therapeutic monitoring, contributing to improved patient care and drug safety in the field of ophthalmology.

Advances in magnetic analytical extraction techniques for detecting antibiotic residues in edible samples.

The widespread use of antibiotics in agricultural and animal husbandry to treat bacterial illnesses has resulted in a rise in antibiotic-resistant bacteria. These bacteria can grow when antibiotic residues are present in food items, especially in edible animal products. As a result, it is crucial to monitor and regulate the amounts of antibiotics in food. Magnetic analytical extractions (MAEs) have emerged as a potential approach for extracting antibiotic residues from food using magnetic nanoparticles (MNPs). Recent improvements in MAEs have resulted in the emergence of novel MNPs with better selectivity and sensitivity for the extraction of antibiotic residues from food samples. Consequently, this review paper addresses current developments in MAE for extracting antibiotic residues from edible samples. It also provides a critical analysis of contemporary MAE practices. The current issues and potential future developments in this field are also discussed, thereby providing a framework for future study paths.

A reverse micelle-mediated dispersive liquid-liquid microextraction coupled to high-performance liquid chromatography for the simultaneous determination of agomelatine and venlafaxine in pharmaceuticals and human plasma.

An eco-friendly dispersive liquid-liquid microextraction mediated with a reverse micelle and coupled to an HPLC-DAD was developed for the simultaneous determination of venlafaxine and agomelatine in dosage forms and human plasma. All the parameters affecting the extraction efficiencies of both drugs were investigated and optimized. Under the optimal conditions, an effective analytes' preconcentration with enrichment factors (EFs) up to 72 was achieved. The linearity of the method was established over the concentration range of 0.50-70.0 and 3.0-100.0 ng/mL for venlafaxine and agomelatine, respectively with good correlation coefficients > 0.998. The method exhibited low detection limits in the range of 0.15-0.89 ng/mL and excellent precisions expressed in %RSD < 3% with average recoveries between 95.0 to 101.0%. The proposed method was employed to analyze the targeted analytes in dosage forms and human plasma samples with favorable characteristics like excellent enrichment, high sensitivity, great accuracy, and high precision. Finally, the greenness of the developed method was assessed using three distinct metric tools, confirming the greenness of the proposed method. The findings of this research could have more general implications for the extraction of other analytes from various matrices.

Spider diagram with greenness evaluation metrics for assessing the new synchronous spectrofluorimetric determination of bicalutamide and resveratrol in human plasma.

A simple, selective, and eco-friendly synchronous fluorescence approach was introduced for the first time for the concurrent estimation of the anticancer combination therapy of bicalutamide and resveratrol. The method relies on measuring the synchronous fluorescence spectra of bicalutamide and resveratrol at 269 and 320 nm, respectively, using Δλ of 60 nm with ethanol as a green diluting solvent. The procedure was optimized, and the method was then fully validated. Excellent linearity (R2 > 0.999) with very low detection limits (0.044 and 2.001 ng/ml) were obtained for both drugs, allowing for their analysis in human plasma. The green profile of the suggested approach was evaluated using the green solvents selecting tool (GSST), spider diagram for greenness index assessment, green analytical process index (GAPI), and Analytical GREEnness (AGREE) metric tools. These assessment metrics confirmed that the developed approach met the maximum number of green requirements, recommending its application as a green substitute for the regular analysis of the concerned drugs in human plasma. The simplicity of sample measurement enables and substantially accelerates the analysis, resulting in lower costs, enhanced procedure accuracy, and lower environmental effect.

Miniaturized ternary deep eutectic solvent-based matrix solid-phase dispersion: A green sample preparation method for the determination of chlorophenols in river sediment.

New ternary deep eutectic solvents were prepared and applied as efficient green dispersing solvents in miniaturized matrix solid-phase dispersion to extract chlorophenols from river sediments for the first time. High-performance liquid chromatography coupled with a photodiode array detector was used to analyze the target analytes. The significant factors affecting the extraction were optimized as follows: dispersant (100 mg), sample (100 mg), ternary eutectic solvents (150 µl), grinding for 1 min, 450 µl of acetonitrile as the elution solvent, and vortex mixing for 20 s. Under the optimal conditions, the method exhibited excellent linearity (correlation coefficient > 0.9980), low limits of detection between 1.039-2.478 µg/g, and extraction recoveries between 93.9% and 99.2%. Furthermore, the method demonstrated excellent precision in the intra- and inter-day analysis with a relative standard deviation below 6%. When compared to conventional extraction techniques, the miniaturized matrix solid-phase dispersion considerably reduced samples and solvent usag, offering important environmental benefits. The green profile of the method was assessed using the complementary green analytical procedure index tool confirming its eco-friendship. The technique was finally employed to evaluate sediment samples from three distinct locations along the Zuibaiji River, indicating its applicability for monitoring environmental samples.

Doped Carbon Dots as Promising Fluorescent Nanosensors: Synthesis, Characterization, and Recent Applications.

Carbon dots (CDs) have recently attracted attention as a new class of photoluminescent materials with promising optical, chemical, and electrical properties. They have been proposed for various applications, such as pharmaceutical sensing, biomarker detection, and cellular bioimaging, by virtue of their economical synthesis, cheap starting materials, water-solubility, excellent chemical stability, good biocompatibility, and low toxicity. Hetero-atom doping is a reliable and adaptable strategy for enhancing the photoluminescence, electrical, and structural characteristics of CDs. Herein, we present an update on heteroatom-doped CDs. Various modern synthetic routes are highlighted, ranging from synthetic processes to doping components. In addition, the optical and biological properties and the possible applications of heteroatom-doped CDs are discussed. This review will provide an overview of recent advances in doped CDs and their expected future perspectives.

Green synchronous spectrofluorimetric method for the simultaneous determination of agomelatine and venlafaxine in human plasma at part per billion levels.

A novel sustainable, simple, sensitive, and green spectrofluorimetric method was developed for the concurrent estimation of venlafaxine and agomelatine in pharmaceuticals and biological fluids. The method relies on synchronous fluorescence spectroscopy, where venlafaxine and agomelatine were measured at 276 and 328 nm, respectively, using Δλ of 20 nm. The potential factors affecting the fluorescence intensity were optimized by the one-factor-at-a-time (OFAT) strategy, where synchronous fluorescence intensity was significantly enhanced using a 1% w/v sodium dodecyl sulfate micellar system. The method was fully validated and exhibited excellent linearity (r2 > 0.999 for both drugs) with very low limits of detection (LODs) in the range of 0.14-0.84 ng/mL. Consequently, the proposed approach was efficiently adopted to analyze the co-administered drugs in their pharmaceuticals and in spiked human plasma with excellent % recovery between 97.4 and 102.2%. Finally, the method's greenness was evaluated using different metric tools, including Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE), which proved its excellent greenness.

Suspect and non-target screening workflow for studying the occurrence, fate, and environmental risk of contaminants in wastewater using data-independent acquisition.

A comprehensive suspect and non-target screening workflow based on liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometer was developed for the detection and identification of contaminants in wastewater using data-independent acquisition. The suspect screening workflow could identify 74 compounds from different classes (mainly pharmaceuticals and pesticides), of which37 compounds were confirmed by reference standards.The remaining 37 compounds were tentatively identified based on MS/MS spectra match. The occurrence and elimination of the identified compounds were studied and discussed in detail. Furthermore, the confirmed compounds were quantified where pharmaceuticals had the greatest overall concentrations in all samples, followed by flame retardants. The non-steroidal antiandrogen, bicalutamide, was detected at the highest concentration (843.9 to 3838 ng/L) at the wastewater effluents, where the flame retardant, tris(2-butoxyethyl) phosphate, exhibited a concentration in the range of 337.2 to 1304.6 ng/L. Consequently, the environmental toxicity and risk of the confirmed compounds were investigated. The pharmaceutical, telmisartan, with the insecticide, fipronil exhibited high-risk quotients ( 600∼1400 and 102∼290, respectively), demonstrating their potential toxicity at ecologically relevant amounts. Finally, multivariate analysis was applied to evaluate the efficiency of wastewater treatment . Principal component analysis was able to clearly discriminate between influent and effluent samples, demonstrating an effective treatment process..

Deep Eutectic Solvents as Promising Green Solvents in Dispersive Liquid-Liquid Microextraction Based on Solidification of Floating Organic Droplet: Recent Applications, Challenges and Future Perspectives.

Deep eutectic solvents (DESs) have recently attracted attention as a promising green alternative to conventional hazardous solvents by virtue of their simple preparation, low cost, and biodegradability. Even though the application of DESs in analytical chemistry is still in its early stages, the number of publications on this topic is growing. Analytical procedures applying dispersive liquid-liquid microextraction based on the solidification of floating organic droplets (DLLME-SFOD) are among the more appealing approaches where DESs have been found to be applicable. Herein, we provide a summary of the articles that are concerned with the application of DESs in the DLLME-SFOD of target analytes from diverse samples to provide up-to-date knowledge in this area. In addition, the major variables influencing enrichment efficiency and the microextraction mechanism are fully investigated and explained. Finally, the challenges and future perspectives of applying DESs in DLLME-SFOD are thoroughly discussed and are critically analyzed.

A green air assisted-dispersive liquid-liquid microextraction based on solidification of a novel low viscous ternary deep eutectic solvent for the enrichment of endocrine disrupting compounds from water.

A green air-assisted dispersive liquid-liquid microextraction based on floating organic droplet solidification (DLLME-SFOD) was introduced for the enrichment of five endocrine disrupting compounds (EDCs) from water using a ternary deep eutectic solvent (TDES) as an extracting solvent prior to their determination by HPLC-PDA. The eutectic solvents were synthesized by combining various fatty acids which can concurrently act as both hydrogen bond acceptors (HBA) and hydrogen bond donors (HBD). Adding a third component to classical two-component eutectic solvents allows to purposefully control density, melting point, and viscosity of the synthesized solvents. Ternary and binary eutectic solvents with C9 acid provided excellent extraction efficiency in comparison with other eutectic solvents with C8 acid, while ternary solvents provided superior extraction efficiency to binary ones. Different variables that could influence the microextraction efficiency were optimized applying central composite face-centered design (CCF). At the optimum conditions, the method had low detection limits ranging from 0.96-2.30 µg/L with a preconcentration up to 134-folds. The method showed good linearity from the linear regression with an excellent correlation coefficient (r2 > 0.999). A good inter- and intraday precision (%RSD < 7%) and%recovery > 90% were achieved proving the method high precision and accuracy. Furthermore, the potential of using the TDES for determining the EDCs from five real water samples was proved through the higher extraction efficiency of the EDCs (90.06-104.43%) with results uncertainty < 20% for most of the compounds. Finally, the method greenness was evaluated by Raynie pictogram, analytical eco-scale, and Green Analytical Procedure Index (GAPI) approaches which confirm the superior eco-friendship of our method in comparison with other reported methods.

Application of D-Limonene as a Bio-based Solvent in Low Density-Dispersive Liquid-Liquid Microextraction of Acidic Drugs from Aqueous Samples.

This study deals with the application of different monoterpenes as relatively green bio-based solvents for low density-dispersive liquid-liquid microextraction (LD-DLLME) of different non-steroidal anti-inflammatory drugs (NSAIDs) from aqueous samples in comparison with conventional halogenated solvents. Results indicated that D-limonene could extract the hydrophobic compounds with higher %recovery compared with other bio-based and halogenated solvents. The LD-DLLME procedure was optimized by applying one-factor-at-a-time (OFAT) followed by central composite face-centered design (CCF) of the response surface methodology (RSM). Under the optimal conditions, the method exhibited good linearity with r ≥ 0.9950 with low LOD as well as LOQ levels in the range of 0.11 to 0.81 and 0.36 to 2.69 ng/mL, respectively. The method was efficiently applied to a variety of real aqueous samples. Finally, the green aspect of our procedure was compared with some reported methods using two green metric tools.

A New HPLC-DAD Method for the Concurrent Determination of Hydroquinone, Hydrocortisone Acetate and Tretinoin in Different Pharmaceuticals for Melasma Treatment.

A new simple and robust HPLC-DAD method was developed for the concurrent analysis of hydroquinone (HQ), hydrocortisone acetate (HCA) and tretinoin (TRN) triple combination for the first time using an Inertsil ODS 3-C18 column (150 mm × 4.6 mm, 5 µm particle size) column with 0.05 M phosphate buffer (pH 5.0) and acetonitrile at a ratio of (10:90, v/v) as a mobile phase, eluted by an isocratic elution mode at a flow rate of 1.0 mL/min and detected at 265 nm. Mefenamic acid was used as an internal standard (I.S.). The method produced linear responses in the concentration range of 10-200, 5-100 and 1-40 µg/mL, with detection limits of 2.01, 1.13 and 0.28 × 10-3 and quantitation limits of 6.11, 3.41 and 0.87 × 10-3 µg/mL for HQ, HCA and TRN, respectively, and a correlation coefficient higher than 0.9998. All validation requirements were satisfied by proving its linearity, precision, accuracy, robustness and specificity. The method was extended for application in triple combination cream, HQ/TRN co-formulated cream and HQ and TRN single ingredient cream with a recovery >97%.

Comparative study of two different chromatographic approaches for quantitation of hydrocortisone acetate and pramoxine hydrochloride in presence of their impurities.

In the present study, we compare the performance of two reversed-phase liquid chromatographic approaches using different eluents either conventional hydro-organic eluent or micellar one for simultaneous estimation of hydrocortisone acetate and pramoxine hydrochloride in presence of their degradants and process-related impurities; hydrocortisone and 4-butoxyphenol, respectively. For conventional reversed-phase liquid chromatography (RPLC), separation of the studied compounds was completed on an Inertsil ODS 3-C18 column (150 mm × 4.6 mm, 5 µm particle size) with a mobile phase consists of 50 mM phosphate buffer (pH 5.0): acetonitrile (50: 50, v/v). For micellar liquid chromatography (MLC), an Eclipse XDB-C8 column (150 mm × 4.6 mm, 5 µm particle size) was chosen for the separation with a green mobile phase consists of 0.15 M sodium dodecyl sulfate, 0.3% triethylamine and 10% n-butanol in 20 mM orthophosphoric acid (pH 5.0). Both methods were extended to analyze hydrocortisone acetate and pramoxine hydrochloride in their co-formulated cream. RPLC was superior to MLC with regard to sensitivity for the estimation of impurities. While, MLC represents an eco-friendly, less hazardous and biodegradable approach. Furthermore, the direct injection of the cream to the system without the need to laborious samples pretreatment, excessive amount of analysis time and/or use of large amount of toxic organic solvents is one of the outstanding advantages of MLC.

Stability-indicating spectrofluorimetric method with enhanced sensitivity for determination of vancomycin hydrochloride in pharmaceuticals and spiked human plasma: Application to degradation kinetics.

Based on investigating the relative fluorescence intensity of vancomycin hydrochloride (VCM) in methanol, a simple, highly sensitive, time-saving and specific spectrofluorimetric method was developed and validated. VCM fluorescence was measured at 335 nm when excited at 268 nm. Excellent linearity is obeyed in the concentration range 1-100 ng/mL with a detection limit of 5.94 pg/mL, a quantitation limit of 18.03 pg/mL and a very good correlation coefficient (r = 0.9999). Our method was applied to analyze VCM in pharmaceuticals as well as spiked human plasma. Moreover, VCM stability was studied when exposed to various degradation conditions such as oxidative, alkaline as well as acidic stress. Acidic and alkaline degradation kinetics of VCM was studied for the first time. The degradation follows pseudo-first-order kinetics. The apparent rate constants and half-life times were calculated. The Arrhenius equation was assessed and the activation energies of the degradation were also calculated. The developed method can be easily applied in quality control laboratories due to its sensitivity, specificity, simplicity and low cost.

Application of quinone-based fluorophore and native fluorescence for the spectrofluorimetric determination of agomelatine in dosage form: Identification of acidic and alkaline- induced degradation products by LC-MS/TOF.

Three spectrofluorimetric methods were developed for agomelatine (AGM) determination in commercial tablets. Method A is based on measuring the native fluorescence of AGM aqueous solution at 230/360 nm. Methods B and C are based on the formation of a charge transfer complex between AGM and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) with measurement of the formed fluorophore at 365/475 nm and 250/304 nm, respectively. The relative fluorescence intensity (RFI) of AGM-DDQ complex was greatly enhanced in the presence of methyl-ß-cyclodextrin (CD). The methods were linear over the concentration ranges of 0.015-0.5, 0.5-8.0, 0.09-6.0 and 0.05-0.2 µg/ml for AGM-native fluorescence, AGM-DDQ, AGM-DDQ-CD and AGM-TCNQ complexes, respectively with excellent correlation coefficients (r = 0.9999). The methods were validated as per the International Conference on Harmonization (ICH) guidelines and all validation requirements were satisfied. The developed methods were extended to the analysis of AGM in commercial tablets. Furthermore, the stability of AGM was studied under different stress conditions (alkaline, acidic, oxidative and photolytic). The potential alkaline and acidic degradation products were identified by LC-MS/TOF.

An ecofriendly green liquid chromatographic method for simultaneous determination of nicotinamide and clindamycin phosphate in pharmaceutical gel for acne treatment.

A new green micellar liquid chromatographic method was developed and validated for the quantitative estimation of nicotinamide (NICO) and clindamycin phosphate (CLD) in bulk and pharmaceutical gel formulation. The analytes are well resolved in less than 6.0 minutes using micellar mobile phase consisting of 0.10M sodium dodecyl sulfate (SDS), 0.3% triethylamine, and 10% 2-propanol in 0.02M orthophosphoric acid at pH 3.0, running through an Eclipse XDB-C8 column (150 mm×4.6 mm, 5 µm particle size) with flow rate 1.0 mL/min. The effluent was monitored with diode array detection at 210 nm. The retention times of NICO and CLD were 3.8 minutes and 5.6 minutes, respectively. The method was validated according to the International Conference on Harmonisation (ICH) guidelines in terms of linearity, limit of detection, limit of quantification, accuracy, precision, robustness, and specificity to prove its reliability. Linear correlation was achieved by plotting the peak area of each drug against its concentration. It was found to be rectilinear in the ranges of 1.0-40.0 µg/mL and 0.5-15.0 µg/mL with limits of detection of 0.06 µg/mL and 0.03 µg/mL and limits of quantification of 0.19 µg/mL and 0.09 µg/mL for NICO and CLD, respectively. The method was successfully implemented for the simultaneous determination of the analytes in their bulk powder and combined gel formulation with high % recoveries. The ease of sample treatment facilitates and greatly expedites the treatment with reduced cost and improved accuracy of the procedure.

Micellar HPLC Method for Simultaneous Determination of Ethamsylate and Mefenamic Acid in Presence of Their Main Impurities and Degradation Products.

An eco-friendly sensitive, rapid and less hazardous micellar liquid chromatographic method was developed and validated for the simultaneous analysis of ethamsylate (ETM) and mefenamic acid (MFA) in the presence of hydroquinone (HQ) and 2,3-dimethylaniline (DMA) the main impurities of ETM and MFA, respectively. Good chromatographic separation was attained using Eclipse XDB-C8 column (150 mm × 4.6 mm, 5 µm particle size) adopting UV detection at 300 nm with micellar mobile phase consisting of 0.12 M sodium dodecyl sulfate, 0.3% triethylamine and 15% 2-propanol in 0.02 M orthophosphoric acid (pH 7.0) at 1.0 mL/min. The analytes were well resolved in <6.0 min, ETM (tR = 1.55 min), HQ (tR = 1.95 min), MFA (tR = 4.55 min) and DMA (tR = 5.80 min). Different validation parameters were examined as recommended by international conference on harmonization (ICH) guidelines. The method was linear over the concentration ranges of 0.5-18.0, 0.5-20.0, 0.01-0.5 and 0.02-0.2 µg/mL with limits of detection of 0.118, 0.159, 0.005 and 0.005 µg/mL and limits of quantification of 0.358, 0.482, 0.014 and 0.015 µg/mL for ETM, MFA, HQ and DMA, respectively. The suggested method was successfully applied for the determination of the two drugs in their bulk powder, laboratory-prepared mixtures, single-ingredient and co-formulated tablets. The obtained results were in accordance with those of the comparison method. The method can also detect trace amounts of HQ and DMA as the main impurities of ETM and MFA, respectively, within the BP limit (0.1%) for both impurities. Furthermore, it is a stability-indicating one for the determination of ETM in its pure form, single-component tablet and co-formulated tablets with other drugs.