Reliable identification of contaminants in complex matrices remains hampered by low-abundance signals, complex spectra, and coeluting isobars in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analyses with data-independent acquisitions. Moreover, wide-scope target screening workflows covering hundreds to thousands of known compounds from reference standards analyses often fail to fully exploit the acquired data, leading to false positives and false negatives. Herein, trapped ion mobility spectrometry (TIMS) was integrated into LC-HRMS, and an enriched database and an analyte-specific framework were introduced for enhanced identification confidence. The database including 1948 contaminants incorporated all MS and MS/MS qualifier ions together with their CCS values and mobility filtering windows, alongside the principal ion. Specific qualifiers were designated as mandatory for the first time by evaluating their relative intensity compared to the principal ion (≥50%), with the established identification points systems being refined accordingly to increase confidence. Regarding TIMS data, ∼2500 CCS values were determined, exhibiting high repeatability (RSD ≤ 0.70%) and interinstrument reproducibility (|ΔCCS|≤ 2%). Comparison with literature data across different IMS-HRMS platforms showed CCS accuracy within 2% for 89% of the ions. In matrix spiking experiments (raptor's eggs, human urine, wastewater), the cleaner mobility-filtered spectra resulted in improved selectivity for several contaminants' qualifiers, which improved detection at low concentrations, minimizing false negatives. Additionally, both differentiation based on CCS values (e.g., atenolol-practolol) and mandatory detection of predefined qualifiers (e.g., prometryn-terbutryn) decreased false positives. By incorporating the TIMS dimension and mandatory qualifiers as additional identification information, this work provides a robust framework for high-throughput environmental monitoring and human exposure assessment.

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.

Coronavirus Disease2019 (COVID-19) can increase sympathetic nervous system activity by inducing systemic inflammation and a cytokine storm. This can result in elevated blood pressure, increased heart rate, and vasoconstriction. A 67-year-old Black male was admitted to the emergency department with a chief complaint of shortness of breath for 2 days. On examination, he exhibited edema and symmetric palpable pulses in his lower limbs. His electrocardiogram revealed left axis deviation, sinus tachycardia, and ST-segment elevation. Reverse transcription-polymerase chain reaction confirmed COVID-19. Hydralazine (5 mg) was administered intravenously immediately. The patient was re-evaluated after 20 min during his stay in the emergency department. After two 5 mg doses of hydralazine, he developed reflex tachycardia. To control heart rate, IV hydralazine was replaced with oral atenolol (50 mg once daily), a β1-blocker that reduces cardiac output. Subcutaneous enoxaparin 80 mg daily was given to prevent thrombotic complications in hospitalized COVID-19 patients. Acute hypertension and COVID-19-induced hypertensive emergencies in patients with preexisting hypertension are typically associated with a worse prognosis.

Understanding the stability of biomarkers during sewer transport is one of the crucial steps when applying wastewater-based epidemiology (WBE) for assessing consumption or exposure to chemicals. Their stability could be impacted by chemical dosing, a common method used to control the generation of hydrogen sulfide in urban sewer networks. Nano zero valent iron (nZVI) has recently attracted attention due to its effectiveness on sulfide and methane removal. However, the impact of dosing nZVI on the transformation of biomarkers in sewers and the consequent influence on WBE estimation remains unknown. This study investigated the impact of nZVI dosage on adsorption and biotransformation processes of 20 pharmaceutical biomarkers in lab-scale sewer reactors. Dosing nZVI (50 mg Fe/L) effectively inhibited the production of sulfide and changed microbial communities in sewer biofilms. There was no adsorption observed when biomarkers interacted with nZVI only, indicating that adsorption to nZVI dosing was not the main mechanism for biomarker transformation. Meanwhile, the duration and amount of dosing nZVI had no impact on stable biomarkers with less 15% loss (e.g. cotinine, OH-cotinine, benzoylecgonine and acesulfame). In contrast, nZVI dosing affected the transformation of inherently moderately stable biomarkers like methamphetamine, 3,4-methylenedioxymethamphetamine, methylone, carbamazepine, ketamine and atenolol. These findings revealed the complex impacts of nZVI on mediating sewer conditions, biological compositions and in-sewer stability of biomarkers. An evaluation framework was applied to jointly consider the impact of nZVI dosing and hydraulic retention time on biomarker stability, which provides new knowledge for WBE's application in dynamic sewer systems.

Concentrations of basic drugs are often overpredicted by physiologically based pharmacokinetic models at very early time points after intravenous dosing. An empirical shallow compartment in our recently published permeability- and perfusion-limited PermQ model improved the prediction of this observed early distribution. This study aimed to determine the impact of glycocalyx, a glycoprotein and glycolipid covering on membranes of red blood cells (RBCs) and endothelium, on the partitioning and distribution of basic drugs. Hyaluronidase (50 μg/mL), heparinase (5 U/mL), and neuraminidase (0.1 U/mL) were used to remove the glycocalyx from rat or human RBCs. Confocal microscopy was used to confirm glycocalyx disruption. RBC partitioning experiments were conducted to obtain partition coefficients (Kp) in RBCs and PBS buffer in the presence or absence of glycocalyx. Experimental Kp for metoprolol and atenolol were scaled with glycocalyx dimensions. The human PermQ model was used to simulate the concentration-time profiles, and results were compared with simulations with empirical Kp values. Confocal microscopy confirmed RBC glycocalyx modification via sialic acid removal. Significant differences were observed for metoprolol and atenolol Kp on human RBC glycocalyx disruption. Modeling suggests that experimental Kp scaled with glycocalyx dimensions, while underestimating empirical Kp estimates, required a similar scalar for both drugs. This underestimation may be due to various reasons, such as incomplete RBC glycocalyx disruption or the RBC glycocalyx being an inadequate surrogate for the endothelial glycocalyx. Our results support the hypothesis that glycocalyx partitioning may partially explain the early distribution of the basic drugs metoprolol and atenolol. SIGNIFICANCE STATEMENT: We explored whether basic drugs can partition into glycocalyx, as this partitioning may explain the observed early time point distribution profile of basic drugs. Erythrocyte glycocalyx was tested as a possible in vitro model for the endothelial cell glycocalyx. Results indicate that glycocalyx partitioning partially explains the observed data for atenolol and metoprolol in humans.

POCIS (Polar Organic Chemical Integrative Samplers) and DGT (Diffusive Gradients in Thin Films) are increasingly used for monitoring trace organic contaminants in aquatic environments. However, the influence of dissolved organic matter (DOM) on these samplers has remained poorly explored. This study investigates the potential influence of humic acids (HA) on the DGT and POCIS sampling performance for selected pharmaceuticals with different physicochemical properties. The sampling of six pharmaceuticals - atenolol (ATE), sulfadiazine (SDZ), trimethoprim (TMP), sulfamethoxazole (SMZ), carbamazepine (CBZ) and diclofenac (DCF) - was compared in the presence and the absence of humic acids at 5, 20 and 50 mgC.L[-1] under controlled laboratory conditions. For SMZ and SDZ, HA had no impact on POCIS and DGT sampling. In contrast, sampling of TMP was significantly influenced by the presence of HA, with a concentration-dependent impact in both POCIS and DGT experiments, and a sampling rate decrease of up to 92%. Finally, the sampling of ATE and CBZ was affected only at the highest HA concentration and just for DGT experiments. These findings highlight the importance of accounting for DOM effects when interpreting passive sampler data.

Bawei Chenxiang Powder (BWCP) is a Tibetan medicine formulation used to treat cardiovascular diseases, has demonstrated clinical efficacy though its material basis remains unclear. In clinical trial, β1-adrenergic receptor (β1-AR) has been recognized as a key therapeutic target in cardiovascular disease treatment. So, in this work, we engineered a fusion protein by linking the kinase domain of epidermal growth factor receptor (EGFR) to the C-terminus of β1-AR, which was subsequently immobilized onto the ibrutinib-modified silica gels. Following column preparation by packing the β1-AR immobilized silica into a stainless-steel column, the specificity and stability of β1-AR column were evaluated through the retention behavior analysis of atenolol, esmolol, and metoprolol for characterization. Then, using the β1-AR column combined with MS/MS, eight BWCP constituents targeting β1-AR were screened and identified: 6-hydroxy-2-(2-phenylethyl) chromone, taxifolin, myristicin, costunolide, dehydrocostus lactone, gallic acid, 3,4-dihydroxybenzoic acid (DHBA), and catechin. The association constants of above screened compounds with immobilized β1-AR were (6.75 ± 0.05) × 10[4], (13.2 ± 0.60) × 10[4], (3.82 ± 0.18) × 10[4], (145.13 ± 1.50) × 10[4], (199.77 ± 0.30) × 10[4], (13.8 ± 0.04) × 10[4], (9.30 ± 0.14) × 10[4], (31.4 ± 0.76) × 10[4] M[-1], respectively. Molecular docking results indicated that the compound-β1-AR complexes stabilization primarily involves hydrogen bonding, van der Waals interactions, Pi-alkyl, and Pi-Pi stacking. A survey of DrugBank showed that catechin have well defined effects against cardiovascular diseases. DHBA and taxifolin are potential drug leads under experimental. These confirmed the reliability of the screened compounds by the immobilized β1-AR. To our knowledge, this work establishes the first systematic identification of BWCP's bioactive components targeting β1-AR, providing a pharmacological foundation for developing novel cardiovascular therapeutics derived from this traditional formulation.