With the increasing detection of emerging pollutants (EPs), such as pharmaceuticals, personal care products, and pesticides, in water bodies, there is a growing research priority to develop efficient methods for their degradation. In the present study, the degradation of 21 EPs from different classes was investigated using horseradish peroxidase (HRP) covalently immobilized onto two photocatalytic supports, TiO2 and ZnO. The hybrid biocatalysts (TiO2-HRP and ZnO-HRP) were used to degrade EPs with and without the presence of a redox mediator, 1-hydroxybenzotriazole (HOBT). The results revealed that not all EPs were equally degraded by HRP enzymes, with some pollutants showing complete, partial, or no degradation. For example, full degradation was achieved for MBT (100%), meloxicam (99.5%) and caffeic acid (98.6%). In contrast, prometryn and MCPA showed only partial degradation, reaching 19.2% and 20%, respectively, and no degradation was observed for fluometuron and atenolol. The addition of the model redox mediator, HOBT, improved the degradation of some pollutants, for example, lincomycin-HCl degradation increased to 36.9%, while trimethoprim degradation improved to 21.5%. Additionally, several pollutants, including roxithromycin, cimetidine, and caffeine, exhibited significantly higher degradation rates when treated with the immobilized HRP enzyme (TiO2-HRP or ZnO-HRP) compared to free HRP. For instance, roxithromycin degradation increased from 0.5% to 58.2% with ZnO-HRP, and for cimetidine, TiO2-HRP improved degradation from 0.3% to 60.1% without HOBT and from 9.0% to 66.7% with HOBT. Molecular docking with the catalytic heme cofactor retained further suggested that degradation trends were not explained by docking score alone, but were influenced by ligand access to the distal heme pocket, molecular planarity, and contact topology near catalytic residues. Finally, an integrated HRP enzyme and chemical oxidation remediation strategy was applied to degrade two pollutants, trimethoprim and DEET. For trimethoprim, TiO2-HRP combined with H2O2 and UV achieved approximately 30% degradation, while for DEET, both TiO2-HRP + H2O2 + UV and ZnO-HRP + H2O2 + UV resulted in around 40% degradation, thereby highlighting a novel application for these hybrid peroxidase-photocatalysts.

The global burden of hypertension and its severe form, resistant hypertension, affecting up to 20% of 1.4 billion adults worldwide, drives mass consumption of multiple drugs. Consequently, antihypertensive agents from different classes enter aquatic environments, yet simultaneous extraction of such chemically diverse drugs remains challenging. This work developed a green analytical method for the simultaneous determination of three model antihypertensive agents from distinct classes, namely, furosemide, atenolol, and lisinopril, in water samples. The method employed dispersive liquid-liquid microextraction using a thymol-based natural deep eutectic solvent selected for its superior hydrophobicity and tunability across varying analyte polarities and acid-base characteristics. Extraction was optimized via Box-Behnken design, followed by HPLC-UV analysis on a phenyl column with gradient elution (detection at 220 nm). The validated method showed good linearity (furosemide: 2-100 µg L[-1], lisinopril: 5-100 µg L[-1], and atenolol: 0.1-50 µg L[-1]) with LODs of 0.18, 0.66, and 0.031 µg L[-1], respectively. The practical applicability of the developed method was evaluated by analyzing real water samples collected from multiple sites across Egypt. The results revealed detectable concentrations of the target pharmaceuticals in several samples, confirming the presence of these contaminants in Egyptian water systems. Specifically, furosemide was detected at 4.72 µg L[-1], atenolol at 0.43 µg L[-1], and lisinopril at 7.21 µg L[-1] in samples collected from Giza. A comprehensive greenness assessment using the GAPI, AGREE, BAGI, and EVG tools confirmed strong alignment with sustainable chemistry principles. By enabling multi-class extraction of antihypertensive drugs with a low-ecological-footprint NADES-based protocol, this method addresses a critical gap as no prior NADES-based method exists for these three therapeutic classes together, supporting environmental monitoring and clean water objectives.

This study presents a sustainable chemometric-assisted UV spectrophotometric strategy for the simultaneous determination of candesartan cilexetil (CAN), chlorthalidone (CTL) and amlodipine (AML) in laboratory-prepared mixtures and commercial pharmaceutical formulations. Owing to the extensive spectral overlap of the three drugs in the UV region, conventional spectrophotometric methods are inadequate for their direct simultaneous analysis. To address this challenge, multivariate calibration models based on principal component regression (PCR), partial least squares (PLS) and genetic algorithm-optimized partial least squares (GA-PLS) were developed, enabling accurate quantification without prior separation or complex sample preparation. A design of experiments (DoE) approach was employed to construct the calibration set, while an independent validation set was generated using orthogonal array-based Latin hypercube sampling (OALHS) to ensure robust external validation across the concentration domain. The GA-PLS model enhanced predictive performance through effective wavelength selection, reducing spectral redundancy and improving model robustness. Furthermore, variable importance in projection (VIP) analysis was employed to identify the most influential spectral variables and provide insight into the spectral regions contributing to analyte quantification. The developed models exhibited excellent analytical performance, characterized by low calibration errors (root mean square error of calibration [RMSEC] < 0.30), strong predictive ability and satisfactory external validation results (RMSEP = 0.2278-0.4419; RRMSEP = 0.1558-0.3978), with recoveries ranging from 99.0% to 100.0%. The sustainability of the proposed methodology was assessed using the multi-colour assessment (MA) tool according to white analytical chemistry principles, yielding a high whiteness score and demonstrating superior environmental performance compared with conventional chromatographic methods. In addition, the graphical layout tool for analytical chemistry evaluation (GLANCE) visualization framework provided a comprehensive graphical assessment of analytical performance and sustainability metrics. The proposed chemometric strategy offers a rapid, reliable, cost-effective and environmentally friendly alternative for routine quality control of multicomponent pharmaceutical formulations.

An LC-MS/MS method coupled with central composite design (CCD)-optimized dispersive liquid-liquid microextraction (DLLME) was developed and validated for sotalol quantification in human plasma according to ICH M10 guidelines. CCD with response surface methodology systematically evaluated four DLLME parameters - disperser solvent volume, extraction solvent volume, sample pH, and centrifugation time - identifying extraction solvent volume, pH, and disperser volume as dominant factors governing extraction efficiency. Optimal conditions of disperser volume 1200 µL, extraction solvent 300 µL, pH 10.0, and centrifugation time 3 min yielded predicted recovery of 95.29%, experimentally confirmed at 99-103%, with organic solvent consumption of 1.5 mL per sample representing a reduction compared to conventional SPE and LLE approaches. Chromatographic separation was achieved on a Poroshell 120 EC-C18 column (100 × 2.1 mm, 2.7 μm) with 4-min isocratic elution, and quantification employed MRM transitions m/z 273.1→255.1 for sotalol and m/z 267.2→145.1 for atenolol internal standard in positive ESI mode. The method demonstrated excellent linearity (1-1200 ng/mL, r² = 0.9994), sensitivity (LLOQ 1 ng/mL), acceptable accuracy and precision, and comprehensive stability under multiple storage conditions, in full compliance with ICH M10 acceptance criteria. Preliminary pharmacokinetic application in healthy volunteers following single oral 80 mg sotalol administration yielded Cmax 701 ± 53.8 ng/mL, t½ 10.1 ± 1.0 h, and AUC0→∞ 11,713 ± 1,345 ng·h/mL, broadly consistent with published literature values, supporting method applicability for therapeutic drug monitoring. Multi-metric sustainability assessment encompassing AGSA-prep (64/100), AGSA (65.28/100), CaFRI (69/100), BAGI (75.0/100), CACI (69/100), AMRI (71/100), and WECA (81%) demonstrated improved environmental performance relative to conventional extraction approaches, providing comprehensive sustainability characterization of the developed method.

Micelle-based drug delivery systems offer a promising strategy for enhancing the solubility and bioavailability of poorly water-soluble therapeutics. Among these, nonionic surfactants such as Triton X-100 are particularly attractive due to their biocompatibility and capacity to encapsulate structurally diverse small molecules. In this work, all-atom molecular dynamics simulations were employed to investigate the encapsulation of three drugs (aspirin, atenolol, and felodipine) within Triton X-100 micelles. The selected molecules span a broad range of hydrophobicities and hydrogen-bonding capabilities, enabling a systematic comparison of how physicochemical properties influence solubilisation behaviour and micelle morphology. The simulations reveal that drug-micelle interactions are dominated by the hydrophilic ethylene-oxide headgroups, with limited penetration into the hydrophobic core. Hydrophobicity correlates positively with total drug loading; however, deviations from this trend highlight the competing roles of polarity and conformational flexibility. Atenolol, the most polar compound, penetrates deepest into the micelle core and induces the greatest deformation, whereas felodipine's extended aromatic surface stabilises more spherical aggregates. Overall, this work demonstrates that Triton X-100 micelles adapt dynamically to chemically diverse guest molecules. The results establish quantitative structure-property relationships linking molecular features, including hydrophobicity, polarity and topology, to encapsulation efficiency and micelle shape. These insights provide molecular-level understanding of the physicochemical principles governing solubilisation in nonionic micellar systems and support the broader application of molecular simulation as a predictive tool for micelle-based drug delivery formulations.

Pharmaceutical residues are persistent contaminants that resist conventional wastewater treatment and can disrupt ecosystems; however, microorganisms provide a promising biobased solution to transform or mineralize these complex xenobiotics. Whether pollutant-adapted communities maintain their degradative capacity under realistic environmental conditions remains a long-standing debate in environmental biotechnology. Here, microbial consortia enriched in six membrane bioreactors under high pharmaceutical concentration (100 mg/L) retained full biodegradation capacity across a 5000-fold concentration range. After prolonged exposure to six model compounds (atenolol, caffeine, diclofenac, enalapril, ibuprofen, and paracetamol) complete removal occurred for all except diclofenac. Degradation remained efficient even at lower and environmentally relevant concentrations (1 mg/L-20 µg/L) and recovered rapidly upon re-exposure to higher loads (100 mg/L). Metagenomic profiling revealed enrichment of oxygenase-mediated catabolic pathways supporting this resilience. When transferred to a 7 liters bioreactor treating real wastewater, the adapted community removed targeted and untargeted pharmaceuticals, demonstrating robustness, scalability, and strong potential for sustainable micropollutant remediation.

Whey protein dietary supplements (WPDS) are widely used by athletes at all levels to improve recovery between training sessions and competitions. The increasing number of reported cases of athletes who consumed these products and subsequently tested positive in antidoping tests has raised concerns that such products may contain undeclared substances. Diuretics are among the most common adulterants found in dietary supplements, and the presence of any amount of these substances in urine or blood samples is classified as doping. This study aimed to develop a reliable method using high-performance liquid chromatography with UV detection (HPLC-UV) to simultaneously detect the presence of the diuretics chlorothiazide, hydrochlorothiazide, furosemide, amiloride, and chlorthalidone in WPDS. A simple, selective, precise, and accurate method was validated according to ANVISA, FDA, and forensic toxicology guidelines using a C8 column, a 100 mM ammonium acetate buffer, and an acetonitrile mobile phase in a gradient system, with UV detection at 276 nm. The method was applied to the analysis of 21 commercial WPDS samples, and 42.9% tested positive for at least one of the investigated diuretics. Furosemide was the most frequently detected diuretic found in 28.8% (0.20-1.82 mg/g of WPDS) of all analyzed samples, followed by hydrochlorothiazide, detected in 19.0% (0.25-1.40 mg/g of WPDS). These results highlight the importance of screening for adulterants in WPDS before consumption to ensure proper quality control, protect consumer safety, and prevent unintentional doping cases.

The safety of pharmaceutical products is critically influenced by the presence of impurities and degradation products. Aniline (ANN) is a very toxic degradation product of atorvastatin (ATN), which can cause life-threatening diseases such as methemoglobinemia. For the first time, a comprehensive artificial intelligence study using molecular docking was applied to assess the ANN-induced methemoglobinemia by simulating different binding energies in different pockets of cytochrome P450 (CYP 1A2), revealing the most suitable position leading to toxicity. Moreover, environmental concerns have become increasingly important due to the toxic effects of the excessive use of organic solvents in chromatographic separation systems. Accordingly, greener surfactant systems comprising sodium dodecyl sulfate (SDS) and polyoxyethylene-23-lauryl ether (Brij-35) were employed as safer alternatives were used for the quantitation of ANN in the presence of salicylic acid as an aspirin impurity alongside four widely used cardiovascular drugs of aspirin (APN), atenolol (AEN), atorvastatin calcium (ATN), and losartan potassium (LSN) in pure form and pharmaceuticals. The method validation was done according to the International Conference for Harmonisation (ICH) guidelines with linearity ranges of (10-200), (5-140), (5-100), (5-130), (0.5-40), and (0.5-30) µg mL-1 for APN, AEN, ATN, LSN, SAA, and ANN, respectively, and the results obtained were highly accurate. The greenness of the proposed method was ascertained using the green analytical procedure index: score (0.80), blue applicability grade index: score (0.85), and the Analytical GREEnness calculator. A statistical comparison between the results of our study and the reported method showed no significant difference in precision or accuracy.

In the title mol-ecule, C8H9NO2, which is an isomer of acetamino-phen [N-(4-hy-droxy-phen-yl)acetamide], the acetamide group plane subtends a dihedral angle of 89.95 (5)° with respect to the phenyl ring plane with the -NH2 group directed outward, in contrast to an in vacuo DFT geometry optimization in which the -NH2 group is directed inward. In the extended structure, N-H⋯O hydrogen bonds organize mol-ecules into stacks propagating along [100], with additional hydrogen bonding linking neighboring parallel stacks. A survey of known structures indicates that the structures of 2-phenyl-acetamide mol-ecules with any substitution at the 4-position on the phenyl ring can demonstrate different orientations for the acetamide group ranging from the -NH2 group directed almost completely outward to the -NH2 group directed almost completely inward.

Antihypertensive drugs are more potent when administered in combinations of two or three different classes of drugs. The objective of this study was to evaluate the pharmacokinetic interaction among amlodipine, losartan, and chlorthalidone. A randomized, open-label, four-sequence, four-period, four-treatment, single-dose study was conducted in healthy Korean male subjects, with oral administrations of two tablets of amlodipine 5 mg, one tablet of losartan 100 mg, one tablet of chlorthalidone 25 mg, or co-administration of all three investigational products. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Twenty-six subjects completed the study. The geometric mean ratios and 90% confidence intervals of Cmax and AUClast, respectively, were 1.0928 (1.0412-1.1469) and 1.0360 (0.9958-1.0778) for amlodipine; 1.1016 (0.9136-1.3284) and 1.1606 (1.0885-1.2375) for losartan; 1.0720 (1.0119-1.1356) and 1.0902 (1.0350-1.1148) for EXP3174 (active metabolite of losartan); and 0.9462 (0.8626-1.0379) and 1.0266 (0.9752-1.0807) for chlorthalidone. All the treatments were well tolerated overall. Besides the slight increase in losartan Cmax, the combination therapy did not show clinically significant pharmacokinetic interactions in terms of systemic drug exposure.

This study constructed generalized molecular models for diverse dissolved organic matter (DOM) components (lipids, peptides, carbohydrates, lignin, tannins, low-molecular-weight aromatics/aliphatics) and trace organic contaminants (TrOCs with positive, neutral, and negative charges). Large-scale molecular dynamics (MD) simulations (100 ns, 39 substances) were performed to elucidate cluster structures, surface properties, and aggregation dynamics, with and without an electric field. Four scenarios (Sce) were designed: (i) Sce-1 including atenolol (ATL) and DOM; (ii) Sce-2 including ATL, sulfamethoxazole (SMZ), carbamazepine (CBZ) and DOM; (iii) Sce-3 with the same composition as Sce-1 under an electric field; and (iv) Sce-4 excluding tannic acid (TAN) and humic acid (HA). Results showed that Ca2+, HA, and TAN act as bridging agents for stabilization, with π-π interactions, van der Waals forces, and hydrogen bonding as key drivers. Average radii of gyration were 4.01, 3.95, 4.25, and 4.22 nm in Sce-1 to Sce-4, respectively, while mean hydrogen bond numbers were 2.16, 0.79, 0.04, and 0.27, indicating more dispersed clusters in Sce-3 and Sce-4. In Sce-1 and Sce-2, short-range Coulombic (Coul-SR, -35,000 kJ/mol) and Lennard-Jones (LJ-SR, -1500 kJ/mol) energies yielded negative total non-bonded energies, forming compact aggregates. Experimental validation using river water confirmed simulation results. Adsorption with MIEX® resin (8 mg/L), followed by persulfate oxidation (0.3 g/L) catalyzed by Fe-Cu-Metal-Organic Framework (0.2 g/L), achieved complete ATL removal (20 mg/L) under an electric field. Fluorescence analysis showed 25.8 % peak intensity reduction. Electric fields disrupt clusters and enhance oxidant-mediated TrOC removal, while pre-removing of bridging molecules reduces cluster size for efficient elimination.

Induced RiverBank Filtration (IRBF) systems may provide reliable and safe drinking water, but at the same time the presence of pharmaceutical active compounds (PhACs) residues in surface- and ground-water raises concerns over their potential health and environmental impacts. We present here the first field-based dataset on PhACs in an IRBF system during low-flow conditions, highlighting the fate of these compounds in a highly conductive, organic-matter poor aquifer. Data were gathered in four samplings run over a one month time. Surface water PhACs concentrations remained low and stable (generally lower than 10 ng/L), yet groundwater showed significant variability (from few to one hundred ng/L), with Ibuprofen, Clarithromycin and Diclofenac reaching levels up to 100 times higher, likely due to retardation processes. While Atenolol, Naproxen, and Metformin were rapidly removed, Ibuprofen, Carbamazepine, and Sulfamethoxazole remained detectable at the drinking water well (at about 1 ng/L concentration), likely due to low microbial uptake at low concentrations. All PhACs showed removal rates above 75 %, but Sulfamethoxazole, supporting the effectiveness of IRBF systems, even in advective-dominant aquifers. Increasing travel distances to target wells for improving attenuation may not be a reliable solution, as other sources of contamination may be introduced in the system. Calculated degradation rates were generally higher than in laboratory studies, reinforcing the need for in-situ data, capturing the complexity of aquifer conditions, including subsurface heterogeneities, groundwater flow patterns, and geochemical variability. High-resolution monitoring is essential: monthly sampling risks missing critical processes such as sorption/desorption. The Serchio River IRBF system proved effective at reducing PhACs presence in drinking water well below 0.1 μg/L, highlighting its value as an energy-efficient treatment method. To ensure safe use of IRBF, future research must integrate geochemical, and metabolite tracking information, along with a proactive approach to designing degradable PhACs, hence, reducing the need on downstream treatment systems.