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Clozapine (CLZ); an atypical antipsychotic drug, is well known to have a significant role in managing schizophrenic patients with substance use disorder (SUD). Unfortunately, many patients are deprived of CLZ benefits due to its limited prescription. This is based upon concerns regarding the critical side effects of CLZ in case of overdosing especially, with the lack of accessible therapeutic drug monitoring (TDM) tools. In this contribution, a simple, accurate and sensitive electrochemical method is proposed for CLZ assay in human saliva. Unlike previously reported methods for TDM of CLZ that depends on invasive matrices as plasma and urine, this method employs electrochemical approaches in exploring human saliva as a patient-friendly alternative for assessing CLZ. The proposed method employs differential pulse voltammetry (DPV) with a sensitive and selective Ag-doped ZnO nanoparticles based carbon paste electrode (CPE). The adopted electrochemical sensor has not been previously reported for CLZ determination, despite it offers enhanced sensitivity together with simple synthesis. The synthesized nanoparticles were characterized through Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The developed sensor was optimized and validated as per FDA guidelines of bioanalytical methods. The linear range in saliva was 0.31–3.67 µmol/L and the lower limit of quantitation (LLOQ) was 0.31 µmol/L. The high reliability and applicability of the suggested method has strong potential to be integrated in a point-of-care testing (POCT) device to introduce more accessible TDM that enables smooth TDM of CLZ. Therefore, it opens pathways for broader and safe use of CLZ. Graphical abstract

As a GABA-β receptor agonist, the central muscle relaxant Baclofen (BAC) has a potential of abuse. Unfortunately, the sense of wellbeing and pleasure is obtained at very high BAC doses. This is associated with many life-threating or even fatal cases due to neurological and respiratory failures. Moreover, having narrow therapeutic index makes BAC a high-risk drug. This is potentiated in case of long-treatment regimen or off-label use in smoking and alcohol cessation protocols. Until now, there is no rapid diagnostic test available for BAC screening. Therefore; It is quite difficult to routinely monitor cases on BAC regimen. On the other hand, smartphone-based colorimetric point of care testing (POCT) is displacing conventional analytical approaches in the detection and assay of abused drugs as well as therapeutic drug monitoring. It offers on-site, rapid, easy, affordable and interpretable analysis. Incorporating smartphone as a portable device facilitates its application, especially in remote areas and low-income countries. For the first time, the current work presents a smartphone-based colorimetric POCT for BAC analysis in urine without interference from urine matrix. It depends on BAC reaction with naphthoquinone sulfonate (NQS) in highly alkaline aqueous medium. The developed color was captured in a customized photo box using smartphone camera. Then, intensity of the blue channel was measured by a software application “Color Analyzer”. All parameters were optimized with respect to the colorimetric reaction, photographing and smartphone-based analysis. All parameters were successfully investigated according to FDA guidelines for bioanalytical method validation. Also, all POCT criteria were considered as per WHO requirements. This method could determine BAC, linearly, from 0.02 to 0.21 mmol L−1 in urine. Moreover, LLOQ was lower than the expected BAC therapeutic concentrations in urine. The proposed method proved high reliability and suitability to analyze BAC in urine. This strongly recommends its routine application in screening BAC abusers and BAC therapeutic monitoring.

In this work, we develop chitosan/xylan-coated magnetite (CsXM) nanoparticles as eco-friendly efficient adsorbents for the facile removal of contaminants from water. Characterization of CsXM using Fourier Transform Infra-Red (FTIR) Spectroscopy, Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Transmission Electron Microscopy (TEM), Zeta potential measurements, and Brunauer-Emmet-Teller (BET) analysis, confirmed the successful preparation of a chitosan/xylan complex coated over magnetite, which is characterized by being mesoporous, thermally stable and of neutral charge. Three contaminants, Pb(II), salicylic acid (SA), and congo red (CR), were chosen as representative pollutants from three major classes of contaminants of emerging concern: heavy metals, pharmaceuticals, and azo dyes. Pb(II), SA, and CR at initial concentrations of 50 ppm were removed by 64.49, 62.90, and 70.35%, respectively, on applying 6 g/L of CsXM. The contaminants were successfully removed in ternary systems, with Pb (II) and SA being more competitive in their adsorption than CR. Adsorption followed the Freundlich isotherm model and the pseudo-second order kinetic model, while the binding was suggested to occur mainly via chemical chelation for Pb(II) and physical interaction for SA and CR, which demonstrates the multifunctional potential of the nanoparticles to capture different contaminants regardless of their charge.

Despite the effectiveness of activated carbon as an adsorbent for many contaminants in water, it suffers from poor handling and regeneration along with difficulty of separation from water after application. Our research aims to develop activated carbon-based adsorbents with enhanced stability and adsorption properties through incorporating biopolymers such as xylan and pectin and coating them over magnetite. The mesoporous adsorbents, as measured by Brunauer–Emmett–Teller analyzer, successfully adsorbed the pharmaceutical emerging contaminants of fluoxetine and famotidine with respective maximum adsorption capacities of 90.9, 42.9 mg/g for the xylan-incorporated nanocomposite, and 114.9, 53.5 mg/g for the pectin-incorporated ones, which are the highest capacities reported for these drugs to date. Thermogravimetric analysis and zeta potential measurements in acidic and basic media showed superior thermal and chemical stability for the developed nanocomposites over bare activated charcoal coated magnetite. Incorporating the biopolymers improved the regenerability of the nanocomposites, as confirmed by estimating the equilibrium dissociation constants. High Performance Liquid Chromatography measurements on adsorption in binary systems of the two drugs in distilled water and spiked tap water showed a decrease in percent removal compared to single systems owing to competitive adsorption between the two drugs.

The cardioprotective drug cyclocreatine phosphate has been awarded Food and Drug Administration-orphan drug designation for the prevention of ischemic injury to enhance cardiac graft recovery and survival in heart transplantation. Cyclocreatine phosphate is the water-soluble derivative of cyclocreatine. Estimating the levels of Cyclocreatine phosphate, Adenosine triphosphate, Creatine Phosphate, Creatine and Cyclocreatine helps us in understanding the energy state as well as evaluating the heart cells’ function. The quantification of endogenous compounds imposes a challenging task for analysts because of the absence of a true blank matrix, whose use is required according to international guidelines. Recently, the International Council for Harmonization issued a new guideline that contains guidance on the validation of methods used to quantify endogenous components, such as the background subtraction approach that was employed in our current study. Specifically, we developed and validated a sensitive, reliable and accurate liquid chromatography-tandem mass spectrometry assay to determine simultaneously the levels of mentioned endogenous compounds in rat heart tissue. Tissue samples were prepared by protein precipitation extraction using water: methanol (1:1). Using Ultra Performance Liquid Chromatography, Chromatographic separation was achieved with ZORBAX Eclipse Plus C18 4.6 × 100 mm,3.5 μm column and conditions as following: ammonium acetate (pH 8.5): acetonitrile, 70:30 mobile phase, 0.7 mL/min flow rate and 25 °C temperature. Electrospray ionization mass detector with Multiple reaction monitoring mode was then employed, using both positive and negative modes, Analysis was carried out using 5.00–2000.00 ng/mL linear concentration range within 2 min for each analyte. According to Food and Drug Administration guidelines for bioanalytical methods, validation was carried out. We investigated the matrix effect, recovery efficiency and process efficiency for the analyte in neat solvent, postextraction matrix and tissue. The results stated mean percentage recoveries higher than 99%, accuracy 93.32–111.99%, and Relative Standard Deviation (RSD) below 15% within the concentration range of our study which indicated that target analytes’ stability in their real matrix is sufficient under the employed experimental conditions.HighlightsDevelopment of a validated LC‒MS/MS method to quantify levels of CCrP, ATP, CrP, Crt, and CCr, simultaneously.LC‒MS/MS method is sensitive, simple and suitable for preclinical trials for CCrP quantitation in different biological fluids.Validated method with good selectivity, linearity, and stability for CCrP in the rat heart.Efficient CCrP quantitation to improve outcomes for heart transplant patients.

Background Endotoxin is a major process-related impurity that can act as a strong immunostimulant leading to fever and hypotensive shock. Thus, the US FDA and international quality standards strictly direct the biologics manufacturers to control the endotoxin contamination during the purification process. In this work, a developed method for biologics purification from acquired endotoxin contamination is introduced. This is accomplished by the preparation of dextran-coated magnetic nanoparticles using a facile rapid co-precipitation method. Results The resulting magnetic nanoparticles (MNPs) are characterized by dynamic light scattering, transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, and vibrating sample magnetometry. The dextran-coated magnetic nanoparticles are further coupled to either polymyxin B or histidine to provide a positively charged ligand which enhances the affinity to the negatively charged endotoxin. Both ligands-coupled MNPs are tested for purification efficiency using the chromogenic kinetic assay. The method conditions are optimized using a two-level factorial design to achieve best purification conditions of the contaminated biologics and indicated endotoxin removal percentage 85.12% and maximum adsorption capacity of 38.5 mg/g, for histidine-coupled MNPs. Conclusions This developed method is introduced to serve biologics manufacturers to improve their manufacturing processes through providing a simple purifying tool for biologics from acquired endotoxin contamination. Graphical Abstract

Novel magnetite nanoparticles (NPs) modified with pectin coating were fabricated, characterized, and evaluated as potential draw solute in a forward osmosis (FO) process for water desalination applications. The prepared NPs had a spherical shape with an average diameter of 200 nm and saturation magnetization of 23.13 emu/g. Thermogravimetric analysis (TGA) and FTIR spectra elucidated the successful pectin coating on magnetite surface. The potential use of the fabricated NPs in water desalination was conducted via a newly developed lab-scale FO system. Deionized water, saline water (0.2, 0.5, and 1 g% NaCl solution), and real well water (TDS = 0.9 g%) were used as feed solutions. In all experiments, the water flux gradually decreased along with the extension of experimental time and NaCl rejection rate by the FO membrane was measured to be higher than 95%. Moreover, it was found that the pectin-coated magnetite NPs demonstrated to be able to draw clean water across the FO membrane from well water with a remarkable salt rejection of 97%. Thus, it is believed that the proposed FO system using pectin-coated magnetite NPs as draw solute can be a promising technique for desalination of well waters in an environmental-friendly and energy-saving manner.