Drug Research Articles

Contextualising Experiences of Co-Occurring Mental Ill-Health and Substance Use Among Trans, Non-Binary, and Gender Diverse Young People: Implications for Tailored Harm Reduction Approaches.

Though significant research highlights higher rates of mental ill-health and substance use among trans, non-binary and gender diverse (henceforth 'trans') young people, little research has considered patterns, contextual characteristics, and correlates of co-occurring experiences of mental ill-health and substance use among trans young people. Using data from the Trans Pathways study, we used prevalence ratios and age- and gender-adjusted logistic regression models to examine prevalence and differences of co-occurring substance use (past six-month cigarette use, alcohol use, and other drug use) and contextual characteristics of substance use (past six-month solitary alcohol and/or drug use, substance use for coping) by mental ill-health (depression disorder, anxiety disorder, past 12-month self-harm thoughtsand behaviours,suicidal thoughts, planning, and attempt/s). Age- and gender-adjusted models assessed associations between co-occurring depressive and anxiety disorders and recent cigarette, alcohol, and other drug use (six co-occurring items total) and 18 interpersonal stressors. Significantly increased odds of smoking or recentuse of cannabis or sedatives was observed among trans young people reporting depressive disorder, anxiety disorder (aORs ranging 1.8-3.1). Trans young people who reported recent smoking or use of cannabis, inhalants, or sedatives, had 40% to 80% reduced odds of past 12-month self-harm thoughts, self-harm behaviours,suicidal thoughts, and suicide attempt/s (aORs ranging 0.2-0.6). On the other hand, solitary alcohol and/or other drug use and substance use for coping was significantly associated with increased odds of all mental ill-health outcomes. Issues with school, secure housing, and intimate partner abuse were themost robust correlates of co-occurring mental ill-health and substance use. Trans young people using substances, especially cigarettes, cannabis, and sedatives, often so do with co-occurring experiences of depression and anxiety though limited substance use in more 'social' contexts may confer benefits for preventingself-harm and suicide thoughts and behaviours. Continued research in partnership with trans young people is warranted to conceptualise more nuanced and precise conceptualparameters of trans-affirming substance useharm reduction approaches.

Understanding the mechanisms of food effect on omaveloxolone pharmacokinetics through physiologically based biopharmaceutics modeling.

Omaveloxolone is a nuclear factor (erythroid-derived 2)-like 2 activator approved in the United States and the European Union for the treatment of patients with Friedreich ataxia aged ≥16 years, with a recommended dosage of 150 mg orally once daily on an empty stomach. The effect of the US Food and Drug Administration (FDA) high-fat breakfast on the pharmacokinetic profile of omaveloxolone observed in study 408-C-1703 (NCT03664453) deviated from the usual linear correlation between fed/fasted maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) ratios reported for various oral drugs across 323 food effect studies. Here, physiologically based biopharmaceutics modeling (PBBM) was implemented to predict and explain the effect of the FDA high-fat breakfast on a 150-mg dose of omaveloxolone. The model was developed and validated based on dissolution and pharmacokinetic data available across dose-ranging, food effect, and drug-drug interaction clinical studies. PBBM predictions support clinical observations of the unique effect of a high-fat meal on omaveloxolone pharmacokinetic profile, in which the Cmax increased by 350% with only a 15% increase in the AUC. Key parameters influencing omaveloxolone pharmacokinetics in the fasted state based on a parameter sensitivity analysis included bile salt solubilization, CYP3A4 activity, drug substance particle size distribution, and permeability. Mechanistically, invivo omaveloxolone absorption was solubility and dissolution rate limited. However, in the fed state, higher bile salt solubilization led to more rapid dissolution with predominant absorption in the upper gastrointestinal tract, resulting in increased susceptibility to first-pass gut extraction; this accounts for the lack of correlation between Cmax and AUC for omaveloxolone.

International Workers' Day: Consumption Patterns of Morphine, Codeine, and Methamphetamine in Urban and Rural Areas Based on Wastewater-Based Epidemiology.

Wastewater-based epidemiology (WBE) is a reliable means to estimate drug consumption in a specific population. By measuring the concentration of drug residues or metabolites in wastewater, the consumption behavior pattern of a specific population can be deduced. Using the WBE method, the present study, for the first time, continuously monitored the differences in the consumption of morphine (MOR), codeine (CODE), and methamphetamine (METH) in three wastewater-treatment plants in a city and two surrounding villages in Xinjiang, China during International Workers' Day and the following week. The wastewater samples were pretreated by solid-phase extraction and then analyzed by high-performance liquid chromatography-tandem mass spectrometry. Methamphetamine was not detected in rural areas and was detected only on International Workers' Day in urban areas. According to the estimation of per capita consumption, the per capita consumption of MOR, CODE, and METH in urban inhabitants was 12.04 to 23.39, 10.44 to 16.39, and 1.31 mg/day/1000 inhabitants. The per capita consumption of MOR and CODE in rural areas was 5.19 to 8.35 and 2.56 to 3.52 mg/day/1000 inhabitants. The consumption of MOR in urban and rural areas was significantly higher than that of CODE and METH. During International Workers' Day, workdays, and weekends, the consumption of MOR and CODE in urban areas is significantly higher than that in rural areas. Compared with those on weekends, the consumption of urban MOR and CODE increased more during International Workers' Day. The consumption of MOR in urban areas showed a weekend effect. The present study can provide information for subsequent research and government departments. Environ Toxicol Chem 2024;00:1-9. © 2024 SETAC.

Impact of reduced sampling frequency of illicit drug wastewater monitoring in the Netherlands.

Drug consumption estimates are traditionally based on surveys or information from police seizures. Alternatively, residues of illicit drugs in untreated wastewater (influent) can be used to calculate mass loads and subsequently estimate drug consumption in the community throughout the week. For this purpose, wastewater is commonly sampled for seven consecutive days within the Sewage analysis CORe group Europe (SCORE), while other sampling schemes may be implemented in long-term studies outside this consortium. The current study demonstrates how sampling frequency of illicit drug residues in the influent of wastewater treatment plants (WWTPs) affects the derived weekly average. Thirty WWTPs were sampled over the course of 12 years and influents were analyzed for five drugs (metabolites): 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, amphetamine, benzoylecgonine (a metabolite of cocaine), and 11-nor-9-Carboxy tetrahydrocannabinol (THC-COOH). Subsequently, small and large WWTPs were grouped with a threshold of 100,000 inhabitants. After data curation, standardized loads were calculated (mg/d per 1000 inhabitants). Weekly averages of loads of the drug residues were calculated based on six scenarios (sampling one to six weekdays) and compared to the weekly average in the control situation (sampling seven weekdays) in a Monte Carlo simulation. Results indicate that drug residues with more dynamic loads over a week require more frequent sampling. The analysis illustrates that a decreased sampling frequency (4 or 5 days per week) still leads to a representative weekly average for all drugs tested when a deviation up to a factor of 1.25 is deemed acceptable. However, knowledge on typical levels is necessary to define outliers. We therefore recommend to study dynamics in drug residue loads for WWTPs before reducing sampling frequency in long term monitoring programs.

Sequencing of Phosphorodiamidate Morpholino Oligomers by Hydrophilic Interaction Chromatography Coupled to Tandem Mass Spectrometry.

Sequencing of phosphorodiamidate morpholino oligomers (PMOs) by hydrophilic interaction chromatography (HILIC) coupled to tandem mass spectrometry (MS/MS) is reported. The MS/MS analysis was performed using a quadrupole/time-of-flight (Q-ToF) mass analyzer and collision induced dissociation (CID) in negative ion mode. To improve MS sensitivity in negative ion mode, HILIC conditions, including the separation column, mobile phases, and MS parameters, were optimized. Using the developed HILIC-CID-MS/MS method, 100% sequence coverage was achieved for PMOs ranging from 18-mer to 25-mer. Additionally, the method was successfully applied to identifying positional isomers of n - 1 deletion impurities present in PMO drug substances.

An Overview of the Analytical Methods for Products based on Clindamycin and Eco-efficiency Perspectives.

Clindamycin (CLIN), an antibiotic sold in the form of capsules, injectable solution, gel, and lotion, is easily soluble in water and ethanol. However, it lacks eco-efficient methods for evaluating pharmaceutical products. The objective of this review is to provide an overview of the analytical methods present both in the literature and in official compendia for evaluating pharmaceutical matrices based on CLIN in the context of Green Analytical Chemistry (GAC). Firstly, microbiological methods for evaluating the potency of CLIN final products were not found, which already shows the need to develop new methods. Among the methods found, which are all physicalchemical, the most used method is HPLC (71%) followed by UV-Vis (14%). Among the targets of the methods, capsules and raw materials were the most studied (33% each). Among the choices of analytical conditions for the methods, acetonitrile is the preferred solvent (27.7%), even though CLIN is easily soluble in ethanol. Thus, the gap in eco-friendly and sustainable analytical methods is a reality and an opportunity for analytical development centers to provide means for evaluating the quality of CLIN-based products.

Development of a Stable Lyophilized Cyclophosphamide Monohydrate Formulation Using Non-Aqueous Solvents.

To ensure product stability, it is critical to maintain the monohydrate state of cyclophosphamide following lyophilization, as this is the most stable solid form of the Cyclophosphamide. On the other hand, because of their limited aqueous solubility and stability, non-aqueous solvents are preferred for determining the composition and stability of bulk solutions. Hence, the purpose of this study was to use non-aqueous solvents for determining the composition and stability of bulk solutions, and to shorten the lyophilization process by retaining the cyclophosphamide monohydrate. Furthermore, prior to selecting the solvent for the bulk solution consisting of 90:10 tertiary butyl alcohol (TBA) and acetonitrile (ACN), various factors were taken into account, including the freezing point, vapor pressure of solvents, solubility, and stability of cyclophosphamide monohydrate. The concentration of the bulk solution was adjusted to 200mg/mL in order to optimize the fill volume, enhance sublimation rates at lower temperatures during primary drying, and eliminate the need for secondary drying. The differential scanning calorimetry (DSC) measurements of bulk solution were used to improve the lyophilization cycle. The lyophilization cycle opted was freezing at a temperature of -55°C with annealing step at -22°C by which the reconstitution time was significantly reduced. The drying was performed at below - 25°C while maintaining a chamber pressure of 300 mTorr. The complete removal of non-aqueous solvents was achieved by retaining water within the system. The presence of cyclophosphamide monohydrate was confirmed using X-ray diffraction (XRD). The reduction of lyophilization process time was established by conducting mass transfer tests and evaluating the physicochemical properties of the pharmaceutical product. Using non-aqueous solvents for freeze-drying cyclophosphamide is a viable option, and this study provides significant knowledge for the advancement of future generic pharmaceuticals.

Buccal lidocaine mucoadhesive patches for pediatrics’ teething pain: overcoming possible hazards of oral gels

Objectives The utilization of pharmaceutical products in pediatric medicine, while established for use in adults, often presents uncertainties due to differences in application for children. The FDA discourages the use of local anesthetic gels, notably lidocaine, for teething pain in pediatrics due to concerns regarding potential adverse effects if inadvertently swallowed excessively. Therefore, significant attention is being directed towards modifying available marketed products to make them suitable for pediatric use. Here, we introduce mucoadhesive patches that not only have an adjusted dose of lidocaine but also feature a controlled release profile to manage teething pain with prolonged effect. This design helps to prevent issues related to gel liquefaction and swallowing, thereby reducing the potential hazardous side effects of lidocaine in the pediatric population. Methods The study involved the development of controlled-release lidocaine HCl-loaded pellets forming a matrix for inclusion in mucoadhesive patches. Characterization was performed to ensure prolonged drug release, particularly during overnight use, aiming to improve pediatric patient compliance and enable precise dosing. Key findings The mucoadhesive patches exhibited sustained lidocaine release lasting 24 h, potentially offering overnight relief suitable for pediatric application. The analysis of lidocaine content revealed that the developed patches maintained stable levels compared to doses obtained from commercially available oral gels. This finding implies effective pain control without the need for frequent reapplications, alongside controlled doses that decrease the likelihood of side effects. Conclusion The formulated medicated patches demonstrated consistent lidocaine content, effectively controlled drug release, and consequently, reduced the likelihood of undesired side effects when compared to oral gel administration.

Biopharmaceutical studies of a novel sedative sublingual lozenge based on glycine and tryptophan: A rationale for mucoadhesive agent selection

Effective sedative drugs are in great demand due to increasing incidence of nervous disorders. The present work was aimed to develop a novel sublingual sedative drug based on glycine and L-tryptophan amino acids. Carbopol and different hydroxypropyl methylcellulose species were alternatively tested as mucoadhesive agents intended to prolong tryptophan sublingual release time. A model lipid medium of fully hydrated L-α-dimyristoylphosphatidylcholine was used for optimal mucoadhesive agents selection. Simultaneous processes of drug release and diffusion in lipid medium were first investigated involving both experimental and theoretical approaches. Individual substances, their selected combinations as well as different drug formulations were consecutively examined. Application of kinetic differential scanning calorimetry method allowed us to reveal a number of specific drug-excipient effects. Lactose was found to essentially facilitate tryptophan release and provide its ability to get into the bloodstream simultaneously with glycine, which is necessary to achieve glycine-tryptophan synergism. Introduction of a mucoadhesive agent into the formulation was shown to change kinetics of drug-membrane interactions variously depending on viscosity grade. Among the mucoadhesive agents, hydroxypropyl methylcellulose species K4M and E4M were shown to further accelerate drug release, therefore they were selected as optimal. Thus, effectiveness of the novel sedative drug was provided by including some excipients, such as lactose and the selected mucoadhesive agent species. A dynamic mathematical model was developed properly describing release and diffusion in lipid medium of various drug substances. Our study clearly showed applicability of a lipid medium to meet challenges such as drug-excipient interactions and optimization of drug formulations.

Automated particle inspection of continuously freeze-dried products using computer vision

The pharmaceutical industry is progressing towards more continuous manufacturing techniques. To dry biopharmaceuticals, continuous freeze drying has several advantages on manufacturing and process analytical control compared to batch freeze-drying, including better visual inspection potential. Visual inspection of every freeze-dried product is a key quality assessment after the lyophilization process to ensure that freeze-dried products are free from foreign particles and defects. This quality assessment is labor-intensive for operators who need to assess thousands of samples for an extensive amount of time leading to certain drawbacks. Applying Artificial Intelligence, specifically computer vision, on high-resolution images from every freeze-dried product can quantitatively and qualitatively outperform human visual inspection. For this study, continuously freeze-dried samples were prepared based on a real-world pharmaceutical product using manually induced particles of different sizes and subsequently imaged using a tailor-made setup to develop an image dataset (with particle sizes from 50μm to 1 mm) used to train multiple object detection models. You Only Look Once version 7 (YOLOv7) outperforms human inspection by a large margin, obtaining particle detection precision of up to 88.9% while controlling the recall at 81.2%, thus detecting most of the object present in the images, with an inference time of less than 1 s per vial.

Detection of drug residues in bean sprouts by hyperspectral imaging combined with 1DCNN with channel attention mechanism

As a crucial vegetable food in Asia, bean sprouts are widely cultivated. However, the common practice of using plant growth hormones and other drugs to boost yield and prolong storage poses health risks if not handled properly, so we introduce a novel approach for the non-destructive detection of drug residues in bean sprout cotyledons. In this paper, four experimental groups treated with different drugs and one drug-free control group are tested using hyperspectral imaging (400–1000 nm). A binarization mask is created using the maximum interclass variance approach for the region of interest (ROI) extraction. Preprocessing involves Savitzky-Golay (SG) smoothing and standard normalized variate (SNV). Additionally, three feature extraction methods are used to extract spectral features and reduce the redundancy of the data. The processed data are fed into several traditional machine learning models and latest models, as well as one-dimensional convolutional neural network (1DCNN). The overall accuracy of each model shows the two traditional machine learning models, PSO-SVM and ELM, achieve only 92.3 % and 92.6 % respectively. The 1DCNN model, on the other hand, exhibits an accuracy of 95.5 %, which increased to 96.3 % after applying the channel attention mechanism module. Moreover, in comparison with two state-of-the-art models with accuracies of 95.4 % and 96.5 %, respectively, the proposed model demonstrates competitive performance. The results demonstrate that the 1DCNN model significantly outperforms the two reference machine learning models in this hyperspectral classification task, and the integration of a channel attention mechanism further improves the accuracy, highlighting its potential for application in this field.

Mass Balance in Pharmaceutical Stress Testing: A Review of Principles and Practical Applications.

Stress testing (also known as forced degradation) of pharmaceutical drug substances and products is a critical part of the drug development process, providing insight into the degradation pathways of drug substances and drug products. This information is used to support the development of stability-indicating methods (SIMs) capable of detecting pharmaceutically relevant degradation products that might potentially be observed during manufacturing, long-term storage, distribution, and use. Assessing mass balance of stressed samples is a key aspect of developing SIMs and is a regulatory expectation. However, the approaches to measure, calculate, and interpret mass balance can vary among different pharmaceutical companies. Such disparities also pose difficulties for health authorities when reviewing mass balance assessments, which may result in the potential delay of drug application approvals. The authors have gathered input from 10 pharma companies to map out apractical review of science-based approaches and technical details to assess and interpret mass balance results. Key concepts of mass balance are introduced, various mass balance calculations are demonstrated, and recommendations on how to investigate poor mass balance results are presented using real-world case studies. Herein we provide a single source reference on the topic of mass balance in pharmaceutical forced degradation for small molecule drug substances and drug products in support of regulatory submissions with the goal of facilitating a shared understanding among pharmaceutical scientists and health authorities.

Screen-printed electrodes decorated with low content Pt–Ni microstructures for sensitive detection of Zn(II), ascorbic acid and paracetamol in pharmaceutical products and human blood samples

In this study, we report for the first time, a method for simultaneous detection of paracetamol (PA) and its toxic impurities, 4-aminophenol (4-AP), as well as commonly co-formulated drugs, ascorbic acid and zinc (AA and Zn(II)), using screen-printed electrodes (SPEs) as a sensing platform. To improve the electrochemical performance of the SPEs, these are decorated with platinum and nickel microstructures (Pt–Ni), using a simple electrodeposition technique. The structures and morphologies of the synthesized Pt–Ni/SPE electrode were confirmed by FE–SEM, TEM, EDX, XRD and AFM measurements. Furthermore, electrochemical characterization of the as-prepared sensor was investigated using cyclic voltammetry and electrochemical impedance spectroscopy methods. Under optimum conditions, the content of 4-AP, PA, AA and Zn(II) was quantified using cyclic voltammetry, differential pulse voltammetry and square-wave voltammetry techniques. The designed sensor exploits a dual effect, leveraging the efficiency of Pt for Zn(II) detection and Pt–Ni for the detection of 4-AP, AA, and PA. On one hand the as-prepared Pt–Ni/SPE sensor exhibits a linear response towards 4-AP and PA, ranging from 0.5 to 200 μM for both, with detection limits of 0.33 µM and 0.23 µM (S/N = 3) for 4-AP and PA, respectively. On the other hand, it demonstrates a linear response towards PA, AA, and Zn(II), ranging from 0.01 to 0.8 μM for Zn(II), 10 to 1800 μM for AA, and 0.5 to 200 μM for PA, with detection limits of 0.004 µM, 9.0 µM, and 0.15 µM for Zn(II), AA, and PA, respectively. Crucially, the as-fabricated sensor, with its remarkable reproducibility, recovery, long-term stability, and anti-interference capabilities, effectively quantified 4-AP, PA, Zn(II) and AA in both pharmaceutical formulations and human plasma samples.

Dietary Exposure to Pesticide and Veterinary Drug Residues and Their Effects on Human Fertility and Embryo Development: A Global Overview.

Drug residues that contaminate food and water represent a serious concern for human health. The major concerns regard the possible irrational use of these contaminants, since this might increase the amplitude of exposure. Multiple sources contribute to the overall exposure to contaminants, including agriculture, domestic use, personal, public and veterinary healthcare, increasing the possible origin of contamination. In this review, we focus on crop pesticides and veterinary drug residues because of their extensive use in modern agriculture and farming, which ensures food production and security for the ever-growing population around the world. We discuss crop pesticides and veterinary drug residues with respect to their worldwide distribution and impacts, with special attention on their harmful effects on human reproduction and embryo development, as well as their link to epigenetic alterations, leading to intergenerational and transgenerational diseases. Among the contaminants, the most commonly implicated in causing such disorders are organophosphates, glyphosate and antibiotics, with tetracyclines being the most frequently reported. This review highlights the importance of finding new management strategies for pesticides and veterinary drugs. Moreover, due to the still limited knowledge on inter- and transgenerational effects of these contaminants, we underlie the need to strengthen research in this field, so as to better clarify the specific effects of each contaminant and their long-term impact.

Industry's perspective on challenges assessing the in vivo impact of removing titanium dioxide (TiO2) from drug products

The European Commission (EC) has tasked the European Medicines Agency (EMA) to provide a recommendation towards the acceptability of titanium dioxide (TiO2) in pharmaceutical products by early 2024 to inform on final decision in early 2025[1]. Unlike the already implemented ban of TiO2 in foods, removing this excipient from pharmaceutical products will likely have significant impact on the pharmaceutical industry, regulatory agencies, and patients. This commentary explores the challenges facing the pharmaceutical industry tasked with supporting the development and registration of TiO2 free (TF) drug products. Specifically, justification of formulation changes and potential impact to in vitro and in vivo performance, as well as differences in global regulatory comparative dissolution requirements to justify changing to TF drug product are discussed. Particularly, the uncertainties around how a formulation change such as removal of TiO2 from immediate release solid oral dosage forms will be viewed in Europe compared to other regions is discussed. To respond to these challenges and avoid disruption to the medicines supply chain in case in vitro data such as dissolution is either too challenging or insufficient to justify changing to TF product, pharmaceutical companies may have to decide if the level of risk is worth the effort needed to reformulate, develop, and register a new TF product.

Preparation of silver-based metal-organic framework and chitosan hybrid material for removing drug and dye

Pharmaceuticals and personal care products and dyes have low biodegradability and high toxicity, seriously threaten the human health and ecological environment. Therefore, seeking effective removal methods has become the focus of research. In this study, silver-based metal-organic framework (Ag-MOF) and chitosan (CS) hybrid adsorbent (Ag-MOF-CS) was synthesized via solvothermal one-pot synthesis to remove diclofenac sodium (DCF) and acid Red 1 (AR1) from water for the first time. The morphology and structure of Ag-MOF-CS were confirmed by various characterizations. The effect on adsorption was investigated by changing the adsorbent dosage, pH and other conditions. The adsorption kinetics, adsorption isotherms and thermodynamics were analyzed. Ag-MOF-CS showed a high adsorption capacity. And the maximum adsorption capacity of Ag-MOF-CS for DCF and AR1 was 351.75 mg/g and 678.83 mg/g, respectively. The adsorbent bound to DCF and AR1 may via electrostatic forces, π-π interactions, hydrogen bonding. Even after four cycles of Ag-MOF-CS, the DCF removal can still be higher than 80 %. The eco-friendly Ag-MOF-CS demonstrated significant potential for utilization in treating wastewater.

Barriers to blockchain-enabled drug recycling: A TISM-MICMAC approach

Pharmaceutical and personal care products have been recognized as contaminants of emerging concern, and many compounds are entering the environment through non-source points like households. Integrating circular economy principles into the supply chain has been proposed as a sustainable waste minimization strategy. Drug recycling programs facilitate the return of end-of-use medicine from consumers, quality checks, screening for reusability, and redistribution to people in need. In this study, we conceptualize a blockchain-enabled drug recycling (BCT-DR) process and identify the barriers to implementing BCT-DR. The contextual relationships between the barriers are examined using Total interpretive structural modeling(TISM) and classified using the Cross-Impact Matrix Multiplication Applied to Classification (MICMAC) approach. Among the factors considered for the study, inadequate regulatory policies, technological complexity, and data risks are found to be the key barriers to the adoption of BCT-DR. The estimation of the contextual relationships of the barriers to BCT-DR has implications for managers, policymakers, researchers, and health system actors in designing effective interventional strategies to address the barriers to BCT-DR.

Toxic Features and Metabolomic Intervention of Glabrene, an Impurity Found in the Pharmaceutical Product of Glabridin.

Glabridin is a widely used product in the cosmetics and pharmaceutical industry, which is generally isolated and purified from Licorice (Glycyrrhiza glabra) extract in industrial production. It has wide clinical applications, but significant toxicity has also been reported. The purity of glabridin raw material is generally between 90% and 98%. We have identified a toxic impurity, glabrene, in the industrial product glabridin. Our investigation using an AB wild-type zebrafish toxicity test showed that glabrene has a significant lethal effect with an LC10 of 2.8 μM. Glabrene induced obvious malformation and disrupted cartilage development in zebrafish larvae. Furthermore, the compound significantly reduced larval mobility and caused damage to brain neural tissues. Metabolic pathway analysis and neurotransmitter quantification via ELISA indicated abnormal activation of the phenylalanine metabolic pathway, resulting in elevated dopamine and acetylcholine levels in vivo. These findings provide insights into the potential risks of glabrene contamination and offer a new reference point for enhancing safety measures and quality controls in licorice-derived products.

Effect of Early Ciprofloxacin Administration on Growth Performance, Meat Quality, Food Safety, and Metabolomic Profiles in Xueshan Chickens.

To investigate the effects of early administration of ciprofloxacin (CIP) on Xueshan chickens, in this study Xueshan chickens were measured for growth performance, tested for drug residues, evaluated for meat quality, and muscle metabolism changes were explored using a non-target metabolomics approach. Experimental findings revealed that early CIP use did not significantly impact the overall growth rate of Xueshan chickens (p > 0.05). However, notable alterations in meat quality were observed: the CIP-treated group exhibited a significant decrease in muscle pH (pH1 and pH24) and a marked increase in drip loss and moisture content (p > 0.05). No CIP residues were detected in muscle tissue. Untargeted metabolomics analyses unveiled significant alterations in the metabolic profile of market-age chickens following CIP treatment. Both functional enrichment and metabolic network analyses indicated significant effects on the ko01120 (microbial metabolism in diverse environments) and ko00350 (tyrosine metabolism) pathways, implying that CIP treatment may influence chicken meat quality by modulating microbial communities and amino acid metabolism. This study provides a crucial foundation for understanding the impact of antibiotics on meat quality and metabolism in poultry production, offering scientific insights for optimizing antibiotic-use strategies and safeguarding poultry product quality.

Analytical Methods for the Determination of Pharmaceuticals and Personal Care Products in Solid and Liquid Environmental Matrices: A Review.

Among the various compounds regarded as emerging contaminants (ECs), pharmaceuticals and personal care products (PPCPs) are of particular concern. Their continuous release into the environment has a negative global impact on human life. This review summarizes the sources, occurrence, persistence, consequences of exposure, and toxicity of PPCPs, and evaluates the various analytical methods used in the identification and quantification of PPCPs in a variety of solid and liquid environmental matrices. The current techniques of choice for the analysis of PPCPs are state-of-the-art liquid chromatography coupled to mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS2). However, the complexity of the environmental matrices and the trace levels of micropollutants necessitate the use of advanced sample treatments before these instrumental analyses. Solid-phase extraction (SPE) with different sorbents is now the predominant method used for the extraction of PPCPs from environmental samples. This review also addresses the ongoing analytical method challenges, including sample clean-up and matrix effects, focusing on the occurrence, sample preparation, and analytical methods presently available for the determination of environmental residues of PPCPs. Continuous development of innovative analytical methods is essential for overcoming existing limitations and ensuring the consistency and diversity of analytical methods used in investigations of environmental multi-class compounds.