Eco-Friendly Synchronous Spectrofluorimetric Method for Simultaneous Determination of Remdesivir and Acetyl Salicylic Acid in Spiked Human Plasma.

Remdesivir and acetyl salicylic acid are often co-administered medications in the treatment of COVID-19, specifically targeting the viral infection and thromboembolism associated with the condition. Hence, it is essential to establish a technique that enables the concurrent quantification of these pharmaceutical compounds in plasma while also keeping environmentally friendly methods. Accordingly, the aim of this work is to simultaneously determine remdesivir and acetyl salicylic acid through a bioanalytical validated synchronous spectrofluorimetric method with applying principles of green chemistry. Since, the two drugs showed severe overlap after excitation at 242.0 nm, 284.0 nm for remdesivir and acetyl salicylic acid, respectively. The overlap was effectively overcome by using synchronous mode with a wavelength difference (Δλ) of 160.0 nm for remdesivir and 100.0 nm for acetyl salicylic acid. Different parameters have been optimized such as Δλ, solvent, pH and surfactant. A linear calibration was obtained over the concentration range 0.01-4.00 µg/mL for remdesivir and 0.01-3.00 µg/mL for acetyl salicylic acid and the method was precise and accurate. The method was successfully used for the investigation of pharmaceutical formulation and the quantification of the maximum plasma concentration (Cmax) of the two drugs. The method has been evaluated as an excellent green analytical method based on three greenness assessment tools.

Ecofriendly micellar mediated spectrofluorimetric method for ultrasensitive quantification of the antiparkinsonian drug safinamide in pharmaceutical formulation and spiked human plasma.

A novel, highly sensitive and eco-friendly micellar-mediated spectrofluorimetric method was developed and validated for the determination of the novel antiparkinsonian drug safinamide mesylate in the presence of its related precursor impurity, 4-hydroxybenzaldehyde. The proposed approach relies on increasing the inherent fluorescence emission at 296 nm of safinamide, by forming hydrogen bonds between the mentioned drug and sodium dodecyl sulfate in the micellar system using 0.1 N HCl as a solvent, following excitation at 226 nm. A thorough investigation was conducted into the experimental factors affecting spectrofluorimetric behavior of the studied drug. A linearity plot of safinamide over the concentration range of 10.0-1000.0 ng/mL against the relative fluorescence intensities was established. The proposed method demonstrated excellent sensitivity down to the nano-gram level with detection and quantitation limits of 1.91 and 5.79 ng/mL, respectively. The studied drug was effectively determined in Parkimedine® Tablets. Furthermore, the proposed method allows for ultrasensitive quantification of safinamide in spiked human plasma, with satisfactory percentage recovery (98.97-102.28%). Additionally, the greenness assessment using the advanced green certificate classification approach, the complementary green analytical procedure index (Complex-GAPI), and the analytical GREEness metric approach (AGREE), along with the practicality check using the Blue Applicability Grade Index in addition to the all-inclusive overall whiteness evaluation using the RGB-12 model were carried out. The outcomes demonstrated the effectiveness and whiteness of the proposed technique. Clearly, the suggested approach has the advantages of being simple, requiring no pretreatment steps, and relying solely on direct measuring procedures.

Toward an Improved Electrocatalytic Determination of Immunomodulator COVID Medication Baricitinib Using Multiwalled Carbon Nanotube Nickel Hybrid.

The study presents a first electrochemical method for the determination of the immunomodulator drug Baricitinib (BARI), crucial in managing COVID-19 patients requiring oxygen support. A unique electrode was developed by modifying graphite carbon nickel nanoparticles (NiNPs) with functionalized multiwalled carbon nanotubes (f.MWCNTs), resulting in nanohybrids tailored for highly sensitive BARI detection. Comparative analysis revealed the superior electrocatalytic performance of the nanohybrid-modified electrode over unmodified counterparts and other modifications, attributed to synergistic interactions between f.MWCNTs and nickel nanoparticles. Under optimized conditions, the sensors exhibited linear detection within a concentration range from 4.00 × 10-8 to 5.56 × 10-5 M, with a remarkably low detection limit of 9.65 × 10-9 M. Notably, the modified electrode displayed minimal interference from common substances and demonstrated high precision in detecting BARI in plasma and medicinal formulations, underscoring its clinical relevance and potential impact on COVID-19 treatment strategies.

Therapeutic drug monitoring of six contraindicated/co-administered drugs by simple and green RP-HPLC-PDA; application to spiked human plasma.

Therapeutic drug monitoring is an important clinical testing of the drugs to monitor their concentrations in plasma in order to guarantee their optimal impact, and to avoid any side effects resulting from drug-drug interactions. A green reversed-phase high-performance liquid chromatographic method using a photodiode array detector (RP-HPLC-PDA) was developed for the simultaneous determination of three carbapenem antibiotics (Imipenem, ertapenem, and meropenem) with the co-formulated drug (cilastatin) and contraindicated drugs (probenecid and warfarin) in spiked human plasma. The separation was achieved at 25 °C using a gradient elution of a mixture of mobile phase A: methanol and mobile phase B: phosphate buffer (pH 3.0). The photodiode array detector was adjusted at 220 nm. Bioanalytical method validation was carried out as per the FDA guidelines, and the method showed good linearity ranges for the six drugs that included their Cmax levels along with low limits of quantification. Based on the results, the method was found to be accurate and precise; with high % recovery and good % RSD, respectively. The method was successfully applied to spiked human plasma, signifying a good potential to be implemented in future TDM studies of these drugs when co-administered together.

A probe of new molecularly imprinted solid-phase extraction coupled with HPLC-DAD and atomic absorption spectrophotometry for quantification of tetracycline HCl, metronidazole and bismuth subcitrate in combination with their official impurities: Application in dosage form and human plasma.

The integration of molecular imprinting technique with chromatographic one has a great impact on the assay's selectivity and sensitivity. Herein, a molecularly imprinted solid-phase extraction associated with high performance liquid chromatography (MISPE-HPLC) was employed for simultaneous determination of the co-formulated drugs; tetracycline hydrochloride (TET) and metronidazole (MET), in plasma and in their anti-H-pylori drug for the first time. Two sorts of molecularly imprinted polymers (MIPs) were fabricated using TET and MET as the template molecules, while ethylene glycol dimethacrylate and methacrylic acid were used as a cross-linker and a monomer, respectively. The synthesized MIPs were identified using different techniques. The adsorption-desorption capability of each template was investigated towards its corresponding MIP. The extraction conditions of MISPE was optimized with respect to TET/MIP and MET/MIP sorbent. Bismuth subcitrate (BSC), the third co-formulated drug was analyzed in spiked human plasma using an atomic absorption spectrometric (AAS) method. The performance of the developed methods was assured as per ICH guidelines for analyzing the studied drugs in their pharmaceutical dosage form along with two of their official impurities. In addition, bioanalytical method validation was conducted where linearity was achieved at 2.0-40.0 µg mL-1, 2.0-40.0 µg mL-1 and 5.0-80.0 µg mL-1 for TET, MET and BSC, respectively.

Stability-indicating UPLC assay coupled with mass spectrometry for the analysis of vilanterol degradation products in human urine.

Vilanterol is a once-daily dose inhaler prescribed for asthma and chronic obstructive pulmonary disease. This study involved an investigation of vilanterol stability under acidic, basic, oxidative, thermal, and photolytic stress conditions. UPLC method was developed and validated for the analysis of vilanterol with its degradants. The drug was stable under photolytic and thermal stress conditions and degraded under acidic, basic, and oxidative stress conditions. Degradation kinetics was performed for acidic, basic and oxidative stress conditions. Kinetics parameters, K, half-life time (t1/2) and shelf-life time (t90) were assessed, and the degradation followed first order reaction. The method was linear from 0.10 to 100.00 µg mL-1 with accuracy, inter-day and intra-day precision from 99.45 to 100.02%, 0.391-0.694 and 0.041-0.345, respectively. Mass spectrometry was employed to elucidate the structure of the degradants, and the results revealed that certain degradation products were comparable to vilanterol metabolites. The World Anti-Doping Agency has prohibited the presence of vilanterol and its metabolites in athletes' urine except for exercise bronchoconstriction with limited dose. So, quantification of vilanterol in the presence of its degradants was performed in human urine. The results revealed that the method was linear in range of 1.00 to 100.00 µg mL-1. Samples collection and experimental protocol was performed according to the guidelines of the Research Ethics Committee of the Faculty of Pharmacy, the British University in Egypt with approval No. CH-2305.

Potentiometric detection of apomorphine in human plasma using a 3D printed sensor.

Apomorphine is a dopamine agonist that is used for the management of Parkinson's disease and has been proven to effectively decrease the off-time duration, where the symptoms recur, in Parkinson's disease patients. This paper describes the design and fabrication of the first potentiometric sensor for the determination of apomorphine in bulk and human plasma samples. The fabrication protocol involves stereolithographic 3D printing, which is a unique tool for the rapid fabrication of low-cost sensors. The solid-contact apomorphine ion-selective electrode combines a carbon-mesh/thermoplastic composite as the ion-to-electron transducer and a 3D printed ion-selective membrane, doped with the ionophore calix[6]arene. The sensor selectively measures apomorphine in the presence of other biologically present cations - sodium, potassium, magnesium, and calcium - as well as the commonly prescribed Parkinson's pharmaceutical, levodopa (L-Dopa). The sensor demonstrated a linear, Nernstian response, with a slope of 58.8 mV/decade over the range of 5.0 mM-9.8 µM, which covers the biologically (and pharmaceutically) relevant ranges, with a limit of detection of 2.51 µM. Moreover, the apomorphine sensor exhibited good stability (minimal drift of just 188 µV/hour over 10 h) and a shelf-life of almost 4 weeks. Experiments performed in the presence of albumin, the main plasma protein to which apomorphine binds, demonstrate that the sensor responds selectively to free-apomorphine (i.e., not bound or complexed forms). The utility of the sensor was confirmed through the successful determination of apomorphine in spiked human plasma samples.

Swimming exercise versus L-carnosine supplementation for Alzheimer’s dementia in rats: implication of circulating and hippocampal FNDC5/irisin

Recent studies have suggested that irisin may act as a potential neurokine. Exercise and L-carnosine supplementation showed neuroprotective effects in Alzheimer’s disease (AD)–like conditions. However, the regulation of irisin in the hippocampus of streptozotocin (STZ)–induced memory impairment and its relation to insulin signalling remain to be investigated. This study was designed to compare the effect of swimming exercise and L-carnosine intake on serum, CSF and hippocampal irisin in rats received intracerebroventricular (ICV) injection of STZ. Rats were recruited in swimming paradigm, received oral carnosine (100 mg/kg/day) or vehicle treated. After 5 weeks, rats were sacrificed after neurobehavioural testing. CSF and serum irisin were determined. Hippocampal tissues were used to assess expression of FNDC5/irisin, BDNF and proteins related to insulin signalling, in addition to β-amyloid peptide and phosphorylated tau protein levels. We observed decreased hippocampal, but not CSF or serum, irisin in ICV-STZ-injected rats. Exercise and carnosine intake almost normalized hippocampal FNDC5/irisin expression which was associated with reduced soluble β-amyloid peptide and phosphorylated tau protein, improved BDNF and insulin signalling proteins, with corresponding mitigated cognitive impairments. However, hippocampal FNDC5/irisin was not correlated with serum or CSF irisin levels. Histologically, both interventions ameliorated the hippocampal damage in STZ-injected rats. The current study reveals that carnosine is equivalent to exercise in reversing cognitive decline and Alzheimer’s biomarkers. In both interventions, enhancement of hippocampal FNDC5/irisin and insulin signalling may be involved in mediating these neuroprotective effects. (AU)