Degradation Products Research Articles

Development and validation of stability indicating HPTLC method for estimation of Daclatasvir Dihydrochloride in pharmaceutical dosage form

A high-performance thin-layer chromatographic method was developed and validated for estimation of Daclatasvir Dihydrochloride in pharmaceutical dosage form. The proposed method was applied successfully to the pharmaceutical analysis of the recently approved dosage form of Daclatasvir Dihydrochloride which is available in market as a brand name of ‘NALDAC 60’ tablets. The drugs were satisfactorily show peak with RF 0.38 for Daclatasvir Dihydrochloride. Method was validated according to the ICH guidelines. The calibration plot was linear between 50-300 ng per band for Daclatasvir Dihydrochloride. The LOD and LOQ for Daclatasvir Dihydrochloride were found to be 0.171 μg per band and 0.521 μg per band, respectively. Accuracy and precision of the proposed method was evaluated by recovery studies (% recovery for Daclatasvir Dihydrochloride was 99.88%) and intra-day and inter-day precision studies (standard deviation value for precision studies was found to be 0.453). In stability testing, Daclatasvir Dihydrochloride was found susceptible to acid hydrolysis and alkaline degradation. Because the method could effectively separate the drugs from their degradation products, it can be used as a stability indicating method. The proposed validated stability indicating assay for the sensitive determination of the mentioned drugs is suitable for Quality control laboratories as a simple fast economic method. Degradation product of Daclatasvir Dihydrochloride in alkaline condition was carried out.

Handheld point-of-care devices for snakebite coagulopathy: a scoping review.

Venom induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenaemia, bleeding, disability, and death. In remote tropical settings, where most snakebites occur, the 20-minute whole blood clotting test is used to diagnose VICC. Point-of-care (POC) coagulation devices could provide an accessible means of detecting VICC that is better standardised, quantifiable, and more accurate. In this scoping review, the mechanistic reasons that previously studied POC devices have failed in VICC are considered, and evidence-based recommendations are made to prioritise certain devices for clinical validation studies. Four small studies have evaluated a POC international normalised ratio (INR) device in patients with Australian Elapid, Daboia russelii and Echis carinatus envenoming. All of these studies used POC INR devices that rely on a thrombin substrate endpoint, which, unlike laboratory-based INR measurement, is known to underestimate INR in patients with hypofibrinogenaemia. Seventeen commercially available POC devices for measuring INR, activated clotting time (ACT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, and fibrin(ogen) degradation products (FDP) have been reviewed. POC INR devices that detect fibrin clot formation, as well as a novel POC device that quantifies fibrinogen were identified, that show promise for use in patients with VICC. These devices could support more accurate allocation of antivenom, reduce the time to antivenom administration, and provide improved clinical trial outcome measurement instruments. There is an urgent need for these promising POC coagulation devices to be validated in prospective clinical snakebite studies.

Infection, inflammation and hepatic encephalopathy from a clinical perspective.

Hepatic encephalopathy (HE) is a syndrome that is associated with both acute and chronic liver injury. It manifests as a wide spectrum of neuropsychological abnormalities, ranging from subtle impairments in executive higher functions observed in cirrhosis, through to coma in acute liver failure. In acute liver failure, the central role of ammonia in the development of brain oedema has remained undisputed for 130 years. It latterly became apparent that infection and inflammation were profound determinants for the development of severe hepatic encephalopathy, associated with the development of cerebral oedema and intracranial hypertension. The relationship of the development of hepatic encephalopathy with blood ammonia levels in cirrhosis is less clear cut and the synergistic interplay of inflammation and infection with ammonia has been identified as being fundamental in the development and progression of hepatic encephalopathy. A perturbed gut microbiome and the presence of an impaired gut epithelial barrier that facilitates translocation of bacteria and bacterial degradation products into the systemic circulation, inducing systemic inflammation and innate and adaptive immune dysfunction, has now become the focus of therapies that treat hepatic encephalopathy in cirrhosis, and may explain why the prebiotic lactulose and rifaximin are efficacious. This review summarises the current clinical perspective on the roles of inflammation and infection in hepatic encephalopathy and presents the evidence base for existing therapies and those in development in the setting of acute and chronic liver failure.

The solar/chlorine system degradation of iopamidol: Roles of reactive species, degradation pathway, and toxicity

The study systematically examined the changing trends of the percentage contributions of reactive species to the degradation of Iopamidol (IPM) under various conditions in the solar/chlorine system. Results showed that compared with chlorine alone and solar radiation system, the solar/chlorine system had an obvious effect on the degradation of IPM under control experiment conditions. HO• and reactive chlorine species played major roles in the apparent pseudo-first-order rate constants of IPM degradation (kobs). The increase of oxidant dosage significantly promoted the steady-state concentration of RCS and the contributions of those to kobs. The concentrations of various radicals at pH 9 were lower than those of at pH 5, while only the percentage contribution of ClO• on kobs was increased. The presence of Cl- could increase the steady-state concentration of Cl•, which further promoted the kobs. NOM would significantly reduce the steady-state concentration of ClO• and Cl•, which leads to a significant increase in the percentage contribution of Cl2−• to kobs, indicating the important role of Cl2−• on organic removal in real water. HCO3-/CO32- had almost no effect on kobs. The degradation products of IPM were identified through HPLC-MS, and the Fukui function was employed to ascertain the sites of degradation, which were formulated by deiodination reactions and the production of organic radicals. According to structure Activity Relationships Program v.2.2 and acute toxicological tests, byproducts did not exhibit significant toxicity. The findings illustrate that the solar/chlorine system is effective in decomposing IPM into non-toxic and non-hazardous small molecules, with potential applications.

Towards Reducing Food Wastage: Analysis of Degradation Products Formed during Meat Spoilage under Different Conditions

Foodstuffs, particularly perishable ones such as meat, are frequently discarded once the best-before date has been reached, despite the possibility of their continued suitability for human consumption. The implementation of intelligent packaging has the potential to contribute to a reduction in food wastage by enabling the monitoring of meat freshness during storage time independently of the best-before date. The process of meat spoilage is associated with the formation of specific degradation products, some of which can be potentially utilized as spoilage indicators in intelligent packaging. The aim of the review is to identify degradation products whose concentration correlates with meat shelf life and to evaluate their potential use as spoilage indicators in intelligent packaging. To this end, a comprehensive literature research was conducted to identify the factors influencing meat spoilage and the eight key degradation products (carboxylic acids, biogenic amines, total volatile basic nitrogen, aldehydes, alcohols, ketones, sulfur compounds, and esters) associated with this process. These degradation products were analyzed for their correlation with meat shelf life at different temperatures, atmospheres, and meat types and for their applicability in intelligent packaging. The review provides an overview of these degradation products, comparing their potential to indicate spoilage across different meat types and storage conditions. The findings suggest that while no single degradation product universally indicates spoilage across all meat types and conditions, compounds like carboxylic acids, biogenic amines, and volatile basic nitrogen warrant further investigation. The review elucidates the intricacies inherent in identifying a singular spoilage indicator but underscores the potential of combining specific degradation products to expand the scope of applications in intelligent packaging. Further research (e.g., storage tests in which the concentrations of these substances are specifically examined or research on which indicator substance responds to these degradation products) is recommended to explore these combinations with a view to broadening their applicability.

Fungal Enzyme-Responsive Hydrogel Drug Delivery Platform for Triggered Antifungal Release.

Fungal infections can lead to debilitating consequences if they are not treated effectively. Antifungal drugs used to treat these infections can be toxic and overuse contributes to growing antifungal resistance. Candida spp., particularly C. albicans, are implicated in a majority of these infections. Virulent C. albicans produce secreted aspartic proteases (Saps) that aid in pathogen tissue invasion and proliferation at an infected site. Here, fungi-responsive hydrogels are developed that degrade in the presence of Saps to provide a triggered release of encapsulated liposomal antifungals. The hydrogel backbone incorporates a Sap-cleavable peptide sequence enabling Sap-responsive degradation. Hydrogels are found to effectively degrade in the presence of Saps extracted from C. albicans. Encapsulated liposomal antifungals show similar release kinetics as hydrogel degradation products in the presence of Saps, supporting a degradation-dependent release mechanism. Antifungal liposome-loaded responsive hydrogels exhibit successful eradication of C. albicans cultures and remain stable in sterile murine wound fluid. Finally, no significant cytotoxicity is observed for murine fibroblast cells and red blood cells exposed to hydrogel degradation products. These fungi-responsive hydrogels have the potential to be used for local, on-demand delivery of antifungal drugs, for effective treatment of fungal infections while helping to limit unnecessary exposure to thesetherapeutics.

An Advanced Solvent for the Caustic-Side Solvent Extraction of Cesium from Nuclear Waste: Comparing Lipophilic Guanidines for Improved Hydrolytic Stability

ABSTRACT An advanced solvent has been developed for application in the extraction of cesium from alkaline nuclear waste. Four lipophilic guanidines have been compared to arrive at a more hydrolysis-resistant suppressor component of the solvent. Plans call for deployment of the Next-Generation Caustic Side-Solvent Extraction (NG-CSSX) process at industrial scale for separation of radioactive Cs-137 from the legacy salt waste stored at the US Department of Energy Savannah River Site (SRS). In the solvent used in NG-CSSX, an alkyl guanidine “suppressor” component facilitates efficient stripping of the loaded cesium from the solvent. However, as typical of guanidine compounds, the suppressor previously used in the NG-CSSX solvent, N,N‘,N’’-tri(3,7-dimethyloctyl)guanidine (TiDG), suffers from hydrolytic degradation under process conditions. Recently, the sterically hindered alkyl guanidine N,N’-dicyclohexyl-N’’-(10-nonadecyl)guanidine (DCNDG) has been found to offer 8 to 44 times greater hydrolysis resistance than TiDG. Here, the process performance characteristics of the NG-CSSX solvent incorporating DCNDG are determined in comparison with TiDG and two other guanidine suppressors. The solvent has been adjusted in density to accommodate use in the SRS Salt Waste Processing Facility and tested under aggressive bench-scale conditions intended to increase plant throughput. Experiments include the effect of ageing at normal and off-normal temperatures of the distribution of Cs+ through the NG-CSSX process, the fate and effects of guanidine degradation products, suppressor capacity, coalescence times for aqueous-solvent dispersions, tendency for emulsification, third-phase formation, and degree of protonation of the guanidine in stripping. While the chosen structures of the four compared guanidines mainly effect differences in stability, subtle differences in other system properties such as emulsion formation and suppressor capacity provide insight into the function of this important solvent component. In comparison with TiDG and two other guanidines, DCNDG provides greatly increased stability while not compromising the excellent functional properties of the NG-CSSX solvent.

Breaking the Perfluorooctane Sulfonate Chain: Piezocatalytic Decomposition of PFOS Using BaTiO3 Nanoparticles

Per‐ and polyfluoroalkyl substances (PFAS) pose significant environmental and health risks due to their ubiquitous presence and persistence in water systems. Herein, the efficacy of piezocatalysis using barium titanate nanoparticles under ultrasound irradiation for the degradation and defluorination of perfluorooctane sulfonate (PFOS) in water is investigated. The research demonstrates a substantial 90.5% degradation and 29% defluorination of PFOS after 6 h of treatment, highlighting the potential of piezocatalysis as a promising approach for PFAS degradation. Additionally, the quantification of degradation products elucidates the transformation pathways of PFOS, suggesting a stepwise chain‐shortening mechanism. The findings underscore the importance of continued research in optimizing piezocatalytic processes and exploring synergistic approaches with other advanced oxidation methods to effectively address PFAS contamination challenges. These efforts are essential for advancing sustainable water treatment strategies and mitigating the environmental and health hazards associated with PFAS contamination.

Thevetia thevetioides Cardenolide and Related Cardiac Glycoside Profile in Mature and Immature Seeds by High-Resolution Thin-Layer Chromatography (HPTLC) and Quadrupole Time of Flight–Tandem Mass Spectrometry (Q-TOF MS/MS) Reveals Insights of the Cardenolide Biosynthetic Pathway

Thevetia thevetioides is a species within the Apocynaceae family known for containing cardenolide-glycosides, commonly referred to as cardiac glycosides, which are characteristic of this genus. The seeds of the Thevetia species are frequently used as a model source for studying cardiac steroids, as these glycosides can be more readily extracted from the oil-rich seeds than from the plant’s green tissues. In this work, the cardenolide profile of ripe and immature seeds was determined and compared to establish the main differences. Ripe seeds contain six related cardenolides and triosides, with thevetin B being the predominant component. In contrast, immature seeds exhibit a total of thirteen cardiac glycosides, including monoglycosides such as neriifolin and peruvosides A, B, and C, as well as diglycosides like thevebiosides A, B, and C. Some of these compounds have previously been identified as degradation products of more complex cardiac glycosides; however, their presence in immature seeds, as described in this study, suggests that they may serve as biosynthetic precursors to the triosides observed in mature seeds. The glycoside patterns observed via HPTLC are associated with specific chemical structures characteristic of this genus, typically featuring thevetose or acetyl-thevetose at the first position, followed by glucose or gentibiose in di- or trisaccharides, independent of the trioside aglycones identified: digitoxigenin, cannogenin, or yccotligenin. Ripe seeds predominantly contain triosides, including thevetin B, C, and A, the latter of which has not been previously reported.

Green synthesis of Bio-CuS quantum dots by sulfate reducing bacteria for solid-phase photocatalytic degradation of polyethylene film

In this study, CuS quantum dots (QDs) synthesized through biological method were used as photocatalysts for the photocatalytic degradation of polyethylene (PE) plastics. Bio-CuS QDs were synthesized through a green process using sulfate reducing bacteria, while Che-CuS QDs were prepared by chemical precipitation for comparison. The crystal structure, surface morphology, microstructure and optical properties of the samples were detected by XRD, SEM, TEM and UV–Vis DRS. The green synthesis mechanism of Bio-CuS was inferred by analyzing changes in amino acid concentration and the three-dimensional fluorescence spectra of extracellular polymeric substances before and after synthesis. The photocatalytic degradation of PE films by Che-CuS and Bio-CuS was investigated. The weight loss rates of PE+Che-CuS and PE+Bio-CuS were 9.1 % and 12.8 % after 14 d irradiation, respectively, while pure PE was only 1.7 %. Furthermore, SEM, UV–Vis DRS, contact angle, TGA, GPC and FTIR were adopted to characterize the PE film. The results revealed that PE+Che-CuS and PE+Bio-CuS underwent major changes in morphology, transparency, hydrophilicity, thermal stability, molecular weight and functional groups compared with PE, with more pronounced changes observed for PE+Bio-CuS. The quenching experiments of active species showed that h+ and·OH were critical to the PE degradation. The intermediate products of PE degradation were analyzed by GC–MS, and a possible degradation pathway was proposed. In addition, the possible mechanism of photocatalytic degradation of PE films by CuS QDs was proposed. This work provides a green remediation approach to addressing the growing plastic pollution in the environment.

Design, development and characterization of a chimeric protein with disulfide reductase and protease domain showing keratinase activity

Keratin is one of the major components of solid waste, and the degradation products have extensive applications in various commercial industries. Due to the complexity of the structure of keratin, especially the disulfide bonds between keratin polypeptides, keratinolytic activity is efficient with a mixture of proteins with proteases, peptidases, and oxidoreductase activity. The present work aimed to create an engineered chimeric protein with a disulfide reductase domain and a protease domain connected with a flexible linker. The structure, stability, and substrate interaction were analyzed using the protein modeling tools and codon-optimized synthetic gene cloned, expressed, and purified using Ni2+-NTA chromatography. The keratinolytic activity of the protein was at its maximum at 70 °C. The suitable pH for the enzyme activity was pH 8. While Ni2+, Mg2+, and Na+ inhibited the keratinolytic activity, Cu2+, Ca2+, and Mn2+ enhanced it significantly. Biochemical characterization of the protease domain indicated significant keratinolytic activity at 70 °C at pH 10.0 but was less efficient than the chimeric protein. Experiments using feathers as the substrate showed a clear degradation pattern in the SEM analysis. The samples collected from the degradation experiments indicated the release of proteins (2-fold) and amino acids (8.4-fold) in a time-dependent manner. Thus, the protease with an added disulfide reductase domain showed excellent keratin degradation activity and has the potential to be utilized in the commercial industries.

Waste control by waste: A new approach for antibiotic removal and metal reuse from livestock wastewater using ascorbic acid-enhanced CaO2/Cu(II) system

Aiming at the coexistence of antibiotics and Cu(II) in livestock wastewater, a novelty strategy for the simultaneous removal of antibiotics and Cu ions by in-situ utilization of Cu(II) (i.e., CP/Cu(II) and CP/Cu(II)/ascorbic acid (AA) systems) was proposed. The removal rate of florfenicol (FF) in the CP/Cu(II)/AA system was 6.9 times higher than that of the CP/Cu(II) system. CP/Cu(II)/AA system was also effective in removing antibiotics from real livestock tailwater. Simultaneously, the removal of Cu ions in CP/Cu(II) and CP/Cu(II)/AA systems could reach 54.5 % and 15.7 %, respectively. The added AA could significantly enhance the antibiotics degradation but inhibit the Cu ions removal. HO•, O2•-, Cu(III), and •C-R were detected in the CP/Cu(II)/AA system, in which HO• was confirmed as the predominant contributor for FF degradation, and Cu(III) and •C-R also participated in FF elimination. The role of AA could accelerate HO• production and Cu(I)/Cu(II)/Cu(III) cycle, and form •C-R. The degradation products and pathways of FF in the CP/Cu(II)/AA system were proposed and the toxicity of the degradation products was evaluated by the toxicity analysis software (T.E.S.T). The results of this work suggest that without introducing complex catalysts, the feasibility of in-situ utilization of Cu(II) inherently or artificially introduced in livestock wastewater activating CP for antibiotic degradation and Cu ions removal was verified.

TiO2/Ti3C2Tx gel microsphere for efficient photocatalytic degradation of organic pollutant with excellent recycling stability

Enhancing the recycling stability of photocatalysts is crucial for practical applications. The significant loss of powder catalyst materials during the recycling process hampers its degradation rate and results in a low reuse rate. Herein, the in-situ prepared TiO2/Ti3C2Tx (TOTC) heterojunction is embedded in gel microsphere (GMS) as a recyclable photocatalyst TOTC@GMS for efficient photocatalytic degradation of Congo red (CR). The experimental results show that the removal rate can reach 99 % in 120 min without any co-catalysts or sacrificial reagents. The GMS can be recycled after rinsing in deionized water for only 2 min, and the removal rate still maintains over 90 % after 25 cycles. Additionally, under natural sunlight exposure, TOTC@GMS achieves a removal rate of 90 % for CR in real water samples. The degradation mechanism is elucidated through hydroxyl radicals (OH) and superoxide radicals (O2−) as the main reactive species, as confirmed by free radical scavenging and electron paramagnetic resonance (EPR) experiments. The degradation products are further analyzed using high-performance liquid chromatography-mass spectrometry (LC-MS), allowing for the deduction of degradation pathways of CR. Furthermore, a phytotoxicity test confirms the non-toxicity of the organic micromolecules generated after degradation. This study presents a practical strategy to improve the recycling stability of photocatalysts, thereby effectively reducing the cost of wastewater treatment.

Effect of chemical structures and environmental factors on the thermal degradation mechanism of polyimide: Experiments and molecular dynamics simulations

The impact of chemical structure and environment on the thermal stability of polyimide (PI) was examined, and the degradation mechanism was determined using a combination of experiments and molecular simulations. Changes in mechanical properties and thermogravimetric analysis (TGA) were used to characterize the thermal stability of PI. Pyrolysis gas chromatography mass spectrometry (Py-GCMS) and thermogravimetric-infrared spectroscopy (TG-IR) were used to analyze the degradation products both qualitatively and quantitatively. Molecular simulation was employed to analyze the primary bond breakage and thermal degradation pathways of PI, as well as to investigate the effects of the chemical structure, atmosphere, and temperature on degradation properties. The findings indicated that p-benzene-structured 3,3′,4,4′-biphenyltetracarboxylic dianhydride (BPDA)/p-phenylenediamine (PDA) has the best thermal stability, whereas weak bonds like C–O–C in 4,4′-oxydianiline (ODA) and C–N in the 2-(4-aminophenyl)-1H-benzimidazol-5-amine (BIA) imidazole group decrease thermal stability. The formation path of low molecular weight products (CO2, CO, HCN, and NH3) and the potential degradation mechanism of PI were proposed. The process of PI thermal degradation accelerated by oxygen and high temperature was observed at the atomic level. Taken together, this work offers the possibility of monitoring the structural evolution of PI degradation process in real-time.

Metabolism of isodecyl diphenyl phosphate in rice and microbiome system: Differential metabolic pathways and underlying mechanisms

Isodecyl diphenyl phosphate (IDDP) is among the emerging aromatic organophosphate esters (aryl-OPEs) that pose risks to both human beings and other organisms. This study aims to investigate the translocation and biotransformation behavior of IDDP in rice and the rhizosphere microbiome through hydroponic exposure (the duration of hydroponic exposure was 10 days). The rhizosphere microbiome 9-FY was found to efficiently eliminate IDDP, thereby reducing its uptake in rice tissues and mitigating the negative impact of IDDP on rice growth. Furthermore, this study proposed the first-ever transformation pathways of IDDP, identifying hydrolysis, hydroxylation, methylation, methoxylation, carboxylation, and glucuronidation products. Notably, the methylation and glycosylation pathways were exclusively observed in rice, indicating that the transformation of IDDP in rice may be more complex than in microbiome 9-FY. Additionally, the presence of the product COOH-IDDP in rice suggested that there might be an exchange of degradation products between rice and rhizobacteria, implying their potential interaction. This finding highlights the significance of rhizobacteria's role which cannot be overlooked in the accumulation and transformation of organic pollutants in grain crops. The study revealed active members in 9-FY during IDDP degradation, and metagenomic analysis indicated that most of the active populations contained IDDP-degrading genes. Moreover, transcriptome sequencing showed that cytochrome P450, acid phosphatase, glucosyltransferase, and methyltransferases genes in rice were up-regulated, which was further confirmed by RT-qPCR. This provides insight into the intermediate products identified in rice, such as hydrolysis, hydroxylated, glycosylated, and methylated products. These results significantly contribute to our understanding of the translocation and transformation of organophosphate esters (OPEs) in plants and the rhizosphere microbiome, and reveal the fate of OPEs in rice and microbiome system to ensure the paddy yield and rice safety.

Occurrence and distribution of phytic acid and its degradation products in soybeans in China: Analytical challenges

Phytic acid (IP6) and its degradation products lower myo-inositol phosphates exert different impacts on nutrient bioavailability and product quality characteristics. However, information regarding the occurrence of IP6 and its degradation products is scarce. In this work, simultaneous determination of IP6 and its degradation products in soybeans was developed, with emphasis on analysis by UPLC-MS/MS and a BEH Amide column both with hybrid surface technology. The retention and analyte/metal surface interactions issues were effectively addressed without ion-pairing reagents addition or derivatization. This method was applied to analyze soybeans from China. Total contents were 0.44–13.2 mg/g, and IP6 and its degradation product myo-inositol pentakisphosphate (IP5) were the predominant analytes, accounting for over 99%. Accession type significantly affected IP5 content, and landraces had significantly higher IP5 than cultivars. Geographically, the lowest IP6 was concentrated in the Huanghuaihai region. Significant correlations existed between IP6 and longitude, altitude, and annual cumulative sunshine hours. This study provides comprehensive insights into the IP6 and its degradation product profile in soybeans, which will benefit breeding soybeans based on specific requirements.

Comprehensive Evaluation of Cocaine and its Hydroxy Metabolites in Seized Cocaine and a Large Cohort of Hair Samples.

As cocaine is not only incorporated into hair via blood following ingestion but also by external contamination, hair samples are commonly tested for cocaine metabolites to prove ingestion. However, cocaine metabolites can also be present as degradation products in typical street cocaine samples. The present study investigates minor hydroxycocaine metabolites para- and meta-hydroxycocaine together with para- and meta-hydroxybenzoylecgonine in seized cocaine (n=200) and hair samples from routine casework (n=2,389). Analytical results of hair samples were interpreted using an established decision model for the differentiation between actual use and external contamination using metabolic ratios (metabolite to cocaine). They were further examined concerning background of request, hair color, body site of sample collection, sex, and metabolic ratios of the main metabolites (benzoylecgonine, norcocaine, and cocaethylene). All seized cocaine samples were positive for para- and meta-hydroxycocaine with a maximum percentage of 0.025 and 0.052 %, respectively; para- and meta-hydroxybenzoylecgonine were detected in 55 and 56 % of samples with a maximum percentage of 0.044 and 0.024 %, respectively. Analytical results of 424 hair samples (17.7 %) were interpreted as being predominantly from contamination; the majority of these samples were from traffic medicine cases (83.7 %). Metabolic ratios of minor hydroxycocaine metabolites were significantly higher in hair samples interpreted as originating from use than in samples interpreted as caused by contamination. Metabolic ratios for hydroxycocaines were significantly higher in forensic cases compared to abstinence controls and also in black hair compared to blond/gray hair. However, this was not the case for hydroxybenzoylecgonine metabolic ratios. No statistical difference was observed with regard to the donor's sex. Hydroxycocaine metabolic ratios increased significantly with increasing ratios of norcocaine and cocaethylene to cocaine, respectively. The study demonstrates that hydroxycocaine metabolites (including thresholds for their metabolic ratios) must be used for a reliable interpretation of positive cocaine results in hair samples.

Rifampicin and its derivatives: stability, disposition, and affinity towards pregnane X receptor employing 2D and 3D primary human hepatocytes

Rifampicin is a model ligand of the pregnane X receptor (PXR), the nuclear receptor involved in the regulation of cytochrome P450 3A4 (CYP3A4). Rifampicin forms several degradation products and metabolites of which 25-desacetylrifampicin is the most abundant in vivo. Here, we aimed to study both the stability and metabolism of rifampicin in media and 2D and 3D primary human hepatocytes (PHHs). Additionally, we analyzed interactions of rifampicin derivatives with PXR. We described that rifampicin gradually degrades by more than 50 % in the medium partly into quinone over 72 h. We observed 25-desacetylrifampicin in 2D PHHs but not in 3D PHHs. Contrary, rifampicin was converted into quinone in a one-direction process in media of 3D PHHs. The potency of rifampicin and its derivatives to activate human PXR was arranged as follows: 3-formylrifamycin SV > rifampicin quinone > rifampicin > rifampicin N-oxide > 25-desacetylrifampicin, respectively, but none activates mouse and rat PXR. The binding differences between rifampicin and 25-desacetylrifampicin were modeled in silico. Finally, we showed that overexpressed uptake organic anion transporting polypeptide 1B1 (OATP1B1) potentiated activation of PXR by rifampicin and rifampicin quinone, but overexpressed efflux multidrug resistance protein 1 (MDR1) decreased PXR activation by all derivatives.

Construction of multi-functional S-Vacancy-Zn3In2S6/Bi-MOF S-scheme heterojunction containing interfacial chemical bonds for the efficient photocatalytic production of H2O2 and excellent photocatalytic degradation of OTC and TC

Designing outstanding S-scheme heterojunction photocatalysts for eliminating pharmaceutical pollution and energy dilemmas is an effective strategy for tackling the issue of global environmental pollution. Herein, the Zn3In2S6/Bi-MOF S-scheme heterojunction was prepared through a facile in-situ hydrothermal method. The Bi-S bonds were introduced into the interface of an S-vacancy-containing Zn3In2S6/Bi-MOF S-scheme heterojunction, which profoundly boosts migration and separation of photogenerated carriers as the highway for electron transfer. The practical significance of Zn3In2S6/Bi-MOF composites for environmental pollution control was assessed using oxytetracycline (OTC) and tetracycline (TC) as representative pharmaceutical pollutants. Simultaneously, the production performance of H2O2 as a new energy carrier was also evaluated to determine the multi-functionality of the Zn3In2S6/Bi-MOF composite. The H2O2 production rate of optimal proportion photocatalyst reaches 3689.94 μmol/g/h without using the sacrificial agent. In addition, it exhibited a photocatalytic degradation of OTC and TC efficiency of 88.1 % and 65.2 % within 60 min, respectively. The Zn3In2S6/Bi-MOF photocatalytic not only exhibits excellent cyclic stability but also has exceptional anti-interference properties-systematic elucidation of the effects of catalyst dosage, pH, and co-existing substances. The efficient photocatalytic production of H2O2 and the degradation of OTC/TC through Bi-S bonds and VS-modificatory S-scheme charge transfer offer valuable new perspectives for designing photocatalysts.

Impact of Cu content on the activity of TiO2-based catalysts for toluene oxidation

Toluene is one of the most toxic contaminants in industrial waste gases, it can enter the body through the respiratory system and skin. Long-term exposure to it can lead to skin inflammation and neurasthenia, and even cause lesions in organs. Over the years, catalytic oxidation technology has been extensively employed to the remove of toluene, and oxides, especially copper oxide, is considered to be an effective catalyst technology and has been extensively studied. In this work, we introduced CuO as an active species to investigate the impact of Cu content in TiO2@CuO (TC-x, x=1, 2, 3, and 5) catalyst on the activity, reusability, and stability of toluene oxidation. The result demonstrated that the addition of Cu species, facilitating the generation of active oxygen obviously reduced the complete oxidation temperature of toluene. Among them, TC-3 catalyst exhibited the highest activity (T50 = 234 ℃, T90 = 289 ℃, and T100 = 310 ℃, with Ctoluene=1000 ppm, WHSV=20,000 mL/ (g h)), great reusability, and stability for toluene degradation. According to the in-situ DRIFTS, the ultimate degradation products of toluene were CO2 and H2O, which were clean and free of secondary pollution.