Development of an eco-friendly fluorescent probe for mefenamic acid sensing in pharmaceuticals and biofluids.

Mefenamic acid, renowned for its analgesic properties, stands as a reliable choice for alleviating mild to moderate pain. However, its versatility extends beyond pain relief, with ongoing research unveiling its promising therapeutic potential across diverse domains. A straightforward, environmentally friendly, and sensitive spectrofluorometric technique has been developed for the precise quantification of the analgesic medication, mefenamic acid. This method relies on the immediate reduction of fluorescence emitted by a probe upon interaction with varying concentrations of the drug. The fluorescent probe utilized, N-phenyl-1-naphthylamine (NPNA), was synthesized in a single step, and the fluorescence intensities were measured at 480 nm using synchronous fluorescence spectroscopy with a wavelength difference of 200 nm. Temperature variations and lifetime studies indicated that the quenching process was static. The calibration curve exhibited linearity within the concentration range of 0.50-9.00 µg/mL, with a detection limit of 60.00 ng/mL. Various experimental parameters affecting the quenching process were meticulously examined and optimized. The proposed technique was successfully applied to determine mefenamic acid in pharmaceutical formulations, plasma, and urine, yielding excellent recoveries ranging from 98% to 100.5%. The greenness of the developed method was evaluated using three metrics: the Analytical Eco-scale, AGREE, and the Green Analytical Procedure Index.

Different spectrophotometric methods for simultaneous quantitation of Vericiguat and its alkaline degradation product: a comparative study with greenness profile assessment.

Investigations concerning novel drugs and their induced degradation products are necessary for clinical research and quality control in the pharmaceutical industry. Four spectrophotometric techniques have been performed for simultaneous quantitation of Vericiguat (VER) and its alkali-induced degradation product (ADP) without prior separation. Method A is a dual wavelength method (DW) that estimates the absorbance difference at 314-328 nm, and 246-262 nm for VER and ADP; respectively. Method B uses a ratio difference method (RD) to estimate the ratio spectrum's amplitude difference (DP318-342) and (DP284-292) for VER and ADP; respectively. Method C uses a first derivative ratio method (1DD) to estimate the peak ratio spectrum amplitude of the first derivative at 318 and 275 nm for VER and ADP; respectively. Method D uses the mean centering of the ratio spectra (MCR) to estimate amplitude values for VER and ADP at 337 and 292 nm; respectively. In a concentration range of 5.00-50.00 µg/mL for VER and 5.00-100.00 µg/mL for ADP, the methods were validated following ICH criteria and utilized to estimate VER in bulk and its dosage form. The methods' greenness was assessed via three tools: the green analytical procedure index (GAPI), analytical eco-scale, and analytical greenness assessment (AGREE).

A comparative study of green solid contact ion selective electrodes for the potentiometric determination of Letrozole in dosage form and human plasma.

Analysis of drugs clinically and their identification in biological samples are of utmost importance in the process of therapeutic drug monitoring, also in pharmacokinetic investigations and tracking of illicit medications. These investigations are carried out using a variety of analytical methods, including potentiometric electrodes. Potentiometric electrodes are a wonderful solution for researchers because they outperform other methods in terms of sustainability, greenness, and cost effectiveness. In the current study, ion-selective potentiometric sensors were assembled for the aim of quantification of the anticancer drug Letrozole (LTZ). The first step was fabrication of a conventional sensor based on the formation of stable host-guest inclusion complex between the cationic drug and 4-tert-butylcalix-8-arene (TBCAX-8). Two additional sensors were prepared through membrane modification with graphene nanocomposite (GNC) and polyaniline (PANI) nanoparticles. Linear responses of 1.00 × 10-5-1.00 × 10-2, 1.00 × 10-6-1.00 × 10-2 and 1.00 × 10-8-1.00 × 10-3 with sub-Nernstian slopes of 19.90, 20.10 and 20.30 mV/decade were obtained for TBCAX-8, GNC, and PANI sensors; respectively. The developed sensors were successful in determining the drug LTZ in bulk powder and dosage form. PANI modified sensor was used to determine LTZ in human plasma with recoveries ranging from 88.00 to 96.30%. IUPAC recommendations were followed during the evaluation of the electrical performance of the developed sensors. Experimental conditions as temperature and pH were studied and optimized. Analytical Eco-scale and Analytical GREEness metric were adopted as the method greenness assessment tools.

The first validated stability-indicating HPLC/DAD method for quantitation of Vericiguat in its pharmaceutical formulation; Application to degradation kinetic studies.

The stability of innovative drug formulations and the development of appropriate stability-indicating methods remain major focuses of recent pharmaceutical analysis. In the present study, an efficient stability-indicating HPLC-DAD technique has been described and validated for the determination of Vericiguat (VER); a novel oral soluble guanylate cyclase (sGC) stimulator used in heart failure. VER's stability under various stress conditions was examined. It was shown that VER was sensitive to alkaline, oxidative and thermal degradation. Mass spectrometry (MS) in electrospray ionization mode was performed to figure out the structure of the alkaline and oxidative degradation products. Efficient separation of VER and its induced degradation products was accomplished using isocratic elution mode on the Inertsil ODS-C18 column. The mobile phase composed of water: acetonitrile (70:30 v/v) with 0.1% O-phosphoric acid; pH was adjusted to 2.22 and a flow rate of 0.80 mL/min. VER was detected at 332 nm over a concentration range of 2.00-20.00 µg/mL. The retention time was 4.500 ± 0.005 min and the correlation coefficient was 0.9996. Following the International Conference of Harmonization's guidelines, the analysis was validated to be specific, fast, simple, precise and accurate for utilization in routine analysis and quality control of VER in its pharmaceutical formulation. Additionally, the suggested technique was expanded to investigate the kinetics of alkaline, oxidative and dry heat degradation.

Solid-state ion-selective electrodes for the first potentiometric determination of the anti-COVID 19 drug Remdesivir in human plasma; A comparative study.

Establishing sensitive and targeted analytical methodologies for drug identification in biological fluids as well as screening of treatments that can counteract the most severe COVID-19 infection-related side effects are of utmost importance. Here, first attempts have been made for determination of the anti-COVID drug Remdesivir (RDS) in human plasma using four potentiometric sensors. Calixarene-8 (CX8) was used as an ionophore applied to the first electrode (Sensor I). The second had a layer of dispersed graphene nanocomposite coating (Sensor II). (Sensor III) was fabricated using nanoparticles of polyaniline (PANI) as ion-to-electron transducer. A reverse-phase polymerization using polyvinylpyrrolidone (PVP) was employed to create a graphene-polyaniline (G/PANI) nanocomposite electrode (Sensor IV). Surface morphology was confirmed by Scanning Electron Microscope (SEM). UV absorption spectra and Fourier Transform Ion Spectrophotometry (FTIR) also supported their structural characterization. The impact of graphene and polyaniline integration on the functionality and durability of the manufactured sensors was examined using the water layer test and signal drift. In the ranges of concentration of 10-7 to 10-2 mol/L and 10-7 to 10-3, sensors II & IV exhibited linear responses; respectively while sensors I & III displayed linearity within 10-6 to 10-2 mol/L. The target drug was easily detectable using LOD down to 100 nmol/L. The developed sensors satisfactorily offered sensitive, stable, selective and accurate estimate of Remdesivir (RDS) in its pharmaceutical formulation as well as spiked human plasma with recoveries ranging from 91.02 to 95.76 % with average standard deviations less than 1.85. The suggested procedure was approved in accordance with ICH recommendations.

Dietary supplement mislabelling: case study on selected slimming products by developing a green isocratic HPLC method for their quality control.

Nowadays, a huge population consumes Dietary supplements for losing weight. Products are often claimed as botanical blends, yet they aren't necessarily safe. Misleading labels are also very common. Thus, validated analytical methods for a wide range of slimming compounds are highly needed. Herein, we present a simple HPLC/PDA method for the quantitation of seven popular slimming ingredients. Studied compounds were Caffeine, Raspberry Ketone, trans-Resveratrol, p-Synephrine, p-Octopamine, p-Hordenine and 2-phenethylamine. After optimization, separation was carried out on a C18 column and mobile phase was a mixture of Acetonitrile:Water containing 0.1% phosphoric acid (50:50, %v/v). The last compound was eluted at 9.76 min. Separation was efficient showing baseline- separated symmetric peaks, without using any gradient programs, organic mobile phase modifiers or modified stationary phases. Method validation was done following ICH guidelines. Calibration curves were linear over wide concentration ranges and calculated LOD values were in the range 0.02-0.09 µg/mL. Method greenness was assessed using Analytical Eco-scale, GAPI and AGREE metric tools. Further, four random sample products purchased from online supplement stores were assayed. Results proved some mislabeling actions. To support our findings, standard addition was carried out and average % recoveries were 96.67 - 101.44% with standard deviation ≤ 2.83 between measurements.

A validated UHPLC-MS/MS method for simultaneous quantification of some repurposed COVID-19 drugs in rat plasma: Application to a pharmacokinetic study.

Since the emergence of Corona virus disease (COVID-19) in 2019, a number of medications have been developed and tried to combat the pandemic. In the present study, we develop a LC-MS/MS approach to detect and quantify certain COVID-19 candidate drugs in rat plasma, including Hydroxychloroquine, Favipiravir, Oseltamivir, and Remdesivir. The analytes were separated using Ultra High-Pressure Liquid Chromatography (UHPLC) over a 13-minute run on a C18 column. The extraction solvent for the (QuEChERS) quick, easy, cheap, effective, rugged and safe method was methanol, while the clean-up phase was primary secondary amine (PSA). Satisfactory recoveries were achieved for all compounds ranging from 82.39 to 105.87 %, with standard deviations smaller than 15.7. In terms of precision, accuracy, linearity, matrix effect, and stability, the method was validated according to US FDA criteria. The Limit of Detection (LOD) was determined to be between 0.11 and 10 ppb. The approach was further developed for a modest pharmacokinetic research in laboratory rats, and thus can be suitable for therapeutic drug monitoring in clinical cases under the same treatment.

Investigation of a QuEChERS-Based Method for Determination of Polycyclic Aromatic Hydrocarbons in Rat Plasma by GC-MS.

Owing to the toxic effects of polycyclic aromatic hydrocarbons (PAHs) on humans and the environment, their sensitive biomonitoring is essential and significant. In this work, a sensitive, simple and rapid bioanalytical method was established for the simultaneous determination of 13 PAHs in rat plasma depending on QuEChERS (Quick, easy, cheap, effective and rugged method) as a preliminary step and gas chromatography-mass spectrometry (GC-MS) for identification. QuEChERS procedure was optimized where acetonitrile was employed for plasma samples extraction, which was further cleaned using primary secondary amine as the sorbent material. Optimization of GC-MS conditions was performed to produce optimum selectivity of the proposed method. The method was fully validated for rat plasma samples where recoveries, matrix effects, limit of quantitation (LOQ), linearity and precision were evaluated. Linearity range was 5-100 ng/mL for most of the 13 analytes. Average recoveries of the 13 PAHs ranged between 85.57% and 109.64% in fortified rat plasma with standard deviations <8.91 except for anthracene that showed 19.24. The limits of detection and LOQs for the 13 compounds ranged from 0.045 to 0.372 ppb and from 0.137 to 1.128 ppb, respectively. The established method was successfully implemented to perform a minor toxicokinetic study in intraperitoneally dosed rats (0.25 and 2 mg/kg in vegetable oil). The 13 PAHs were tracked in rat plasma samples for 6 h after administration, and most of the target compounds were recognized in plasma samples only at the higher dose.

Quality control of dietary supplements: An economic green spectrofluorimetric assay of Raspberry ketone and its application to weight variation testing.

Although Dietary supplements are readily accessible and extensively used worldwide, they are inadequately regulated and consumers are victims of manufacturers' fraud. Thus, quality regulations are required to ensure safety of products available to the public. We propose the first native spectrofluorimetric quality control assay of raspberry ketone, a popular dietary supplement ingredient for weight loss. This work relies on the constant wavelength synchronous scan of the Raspberry Ketone native fluorescence, overcoming the demerits of conventional excitation/ emission spectra. For the best measurement conditions, several parameters were optimized including Δλ value, diluting solvent, medium pH and the effect of surfactants/ macromolecules. In aqueous medium (Δλ = 110 nm), a linear relationship exists between synchronous fluorescence intensity at peak maximum 405.6 nm and solution concentration in the range 300-1500 ng/mL. Method sensitivity was recorded with LOD and LOQ values 60.63 and 183.72 ng/mL; respectively. Validation was done in accordance to International Conference on Harmonization (ICH) guidelines. This simple procedure was successfully applied to the analysis of Raspberry Ketone in commercially available dietary supplement capsules with average recovery 98.67% ± 1.74 and further extended to weight variation testing following the official United States Pharmacopeial (USP) guidelines. Finally, green assessment was done using the ''Analytical Eco-scale'' tool. The total score was 89/100 points revealing excellent greenness of our proposal. Our proposal is simple, eco-friendly and cheap. It can be conveniently adopted for routine quality control practices especially in developing countries.

Novel potentiometric sensors for the determination of the dinotefuran insecticide residue levels in cucumber and soil samples.

Five new potentiometric membrane sensors for the determination of the dinotefuran levels in cucumber and soil samples have been developed. Four of these sensors were based on a newly designed molecularly imprinted polymer (MIP) material consisting of acrylamide or methacrylic acid as a functional monomer in a plasticized PVC (polyvinyl chloride) membrane before and after elution of the template. A fifth sensor, a carboxylated PVC-based sensor plasticized with dioctyl phthalate, was also prepared and tested. Sensor 1 (acrylamide washed) and sensor 3 (methacrylic acid washed) exhibited significantly enhanced responses towards dinotefuran over the concentration range of 10-7-10-2molL-1. The limit of detection (LOD) for both sensors was 0.35µgL-1. The response was near-Nernstian, with average slopes of 66.3 and 50.8mV/decade for sensors 1 and 3 respectively. Sensors 2 (acrylamide non-washed), 4 (methacrylic acid non-washed) and 5 (carboxylated-PVC) exhibited non-Nernstian responses over the concentration range of 10-7-10-3molL-1, with LODs of 10.07, 6.90, and 4.30µgL-1, respectively, as well as average slopes of 39.1, 27.2 and 33mV/decade, respectively. The application of the proposed sensors to the determination of the dinotefuran levels in spiked soil and cucumber samples was demonstrated. The average recoveries from the cucumber samples were from 7.93% to 106.43%, with a standard deviation of less than 13.73%, and recoveries from soil samples were from 97.46% to 108.71%, with a standard deviation of less than 10.66%. The sensors were applied successfully to the determination of the dinotefuran residue, its rate of disappearance and its half-life in cucumbers in soil in which a safety pre-harvest interval for dinotefuran was suggested.

Multiresidue Analysis of Five Neonicotinoid Insecticides and Their Primary Metabolite in Cucumbers and Soil Using High-Performance Liquid Chromatography with Diode-Array Detection.

A sensitive, selective, and validated HPLC-diode-array detection method was developed for the simultaneous determination of five neonicotinoid insecticides-acetamiprid, imidacloprid, nitenpyram, flonicamid, and thiacloprid-and their primary metabolite, 6-chloronicotinic acid, in cucumbers and soil based on the quick, easy, cheap, effective, rugged, and safe (QuEChERS) technique as a pretreatment procedure. In the QuEChERS procedure, cucumber samples were extracted with acetonitrile and cleaned using C18, whereas soil samples were extracted with an acetonitrile-dichloromethane mixture (1 + 2). The HPLC conditions were optimized by separating neonicotinoids using an acetonitrile-water mixture (25 + 75) and a Synergi Hydro RP C18 column. Matrix-matched calibration standards were prepared in cucumber and soil to eliminate any matrix interference. RSDs were ≤9% in all recovery tests. LODs and LOQs for the five neonicotinoids were in the ranges of 0.006-0.122 and 0.018-0.366 µg/g, respectively. This method was successfully applied to determine residues, the rate of disappearance of the five neonicotinoids from cucumber and soil, and the half-lives of the neonicotinoids.

Simultaneous determination of eight neonicotinoid insecticide residues and two primary metabolites in cucumbers and soil by liquid chromatography-tandem mass spectrometry coupled with QuEChERS.

A new, rapid, sensitive, precise and validated high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) method was developed for the simultaneous determination of eight neonicotinoid insecticides with their two primary metabolites in cucumbers and soil based on QuEChERS as a pretreatment procedure. In QuEChERS procedure, cucumber samples were extracted with acetonitrile and cleaned using (C18 sorbent material), while soil samples were extracted with a mixture of acetonitrile:dichloromethane (8.3:16.7v:v). The LC-MS/MS conditions were optimized to provide good selectivity and specificity of the developed method where neonicotinoids were separated using gradient elution of water and acetonitrile both containing 0.1% formic acid with Gemini C18 column where the last compound was eluted at 9.5min. Average recoveries of the eight neonicotinoids and their metabolites ranged between 81.6% and 95.7% in fortified cucumber samples with relative standard deviations (RSDs) lower than 13.18% and between 80.3% and 104% in fortified soil samples with relative standard deviations (RSDs) lower than 8.44%. The limits of detection (LODs) and quantification (LOQs) for the ten compounds were in the ranges of (0.08-6.06ng/g) and (0.26-20ng/g), respectively. The method was applied successfully to determine residues and rate of disappearance of the eight neonicotinoids from cucumber and soil and their half-lives where a safety pre-harvest interval of 5days for acetampirid, 12days for imidacloprid, 15days for nitenpyram, 12days for thiamethoxam, 5days for flonicamid, 8days for clothianidin, 2days for Dinotefuran, and 1day for thiacloprid were suggested.

New HPLC and fluorometric methods for the determination of pyriproxyfen and pyridalyl insecticide residues in tomatoes.

Two sensitive, selective, and precise methods for the determination of pyriproxyfen and pyridalyl insecticide residues in tomatoes have been developed. The first method is HPLC with UV detection in which pyriproxyfen and pyridalyl were extracted with ethyl acetate and acetone, respectively, followed by cleanup using column chromatography. The recoveries ranged from 86.03 to 94.55 for pyriproxyfen and 95.08 to 99.38% for pyridalyl in tomato samples. The LOD of the method was 0.217 ppm for pyriproxyfen and 0.1866 ppm for pyridalyl. The second method depends on direct fluorometric determination of pyriproxyfen and pyridalyl in acetic and sulfuric acid at excitation and emission wavelengths of 320 and 646 nm, respectively. The recoveries of pyriproxyfen and pyridalyl in tomato samples ranged from 88 to 98% and 86 to 93%, respectively. The LOD of the method was 0.146 ppm for pyriproxyfen and 0.078 ppm for pyridalyl. Both methods were applied successfully to determine residues and rate of disappearance of pyriproxyfen and pyridalyl from tomatoes.