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Precisely detecting trace pesticides and their residues in food products is crucial for ensuring food safety. Herein, a high-performance electrochemical sensing platform was developed for the detection of carbendazim (CBZ) using Co,N co-doped hollow carbon nanocage@carbon nanotubes (Co,N-HC@CNTs) obtained from core-shell ZIF-8@ZIF-67 combined with a poly(3,4-ethylenedioxythiophene) (PEDOT) molecularly imprinted polymer (MIP). The Co,N-HC@CNTs exhibited excellent electrocatalytic performance, benefitting from the synergistic effect of CNTs that provide a large specific surface area and excellent electrical conductivity, Co,N co-doped carbon nanocages that offer high electrocatalytic activity and hollow nanocage structures that ensure rapid diffusion kinetics. The conductive PEDOT-MIP provided specific binding sites for CBZ detection and significantly amplified the detection signal. The sensor showed superior selectivity for CBZ with an extremely low detection limit of 1.67 pmol L -1 . Moreover, the method was successfully applied to detect CBZ in tomato, orange and apple samples, achieving satisfactory recovery and accuracy, thus demonstrating its practical feasibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Effective strategies are required to address food safety issues related to the illegal addition of antihypertensive drugs to food and claims of antihypertensive function. In this study, a novel ultra-high performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of three antihypertensive drugs (azilsartan, candesartan cilexetil, and lacidipine) in 12 food matrices (pressed candies, solid beverages, alternative teas, tea drinks, biscuits, jellies, mixed liquors, oral liquids, medicinal teas, tablets, hard capsules, and soft capsules). Initially, mass spectrometry parameters, such as the collision energies of the three antihypertensive drugs, were optimized. Subsequently, the response intensities and chromatographic separation conditions of the three drugs in different mobile phases were compared. In addition, to enhance the recoveries, various extraction solvents and purification methods, including solid-phase extraction (SPE) columns and the QuEChERS technique, were investigated. In the developed method, sample determination involved three steps. First, the sample was extracted using 0.2% (v/v) formic acid in acetonitrile and then filtered using high-speed centrifugation, in addition, the extracted solution of alternative tea and medicinal tea was purified using the QuEChERS technique. Second, the supernatant was diluted with water, and filtered through a 0.22 μm polytetrafluoroethylene (PTFE) membrane. Finally, the analytes were separated on an Agilent Eclipse Plus RRHD C 18 column (50 mm×2.1 mm, 1.8 μm) using a 5 mmol/L ammonium formate aqueous solution and acetonitrile as the mobile phases under gradient elution conditions and then detected using UHPLC-MS/MS with positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. Methodological validation showed good linear relationships for all three antihypertensive drugs in the investigated concentration ranges, with correlation coefficients ( r 2 ) greater than 0.996. The limit of detection (LOD) and limit of quantification (LOQ) of lacidipine were 0.02 mg/kg and 0.04 mg/kg, respectively, whereas those of the other two drugs were 0.01 mg/kg and 0.02 mg/kg, respectively. In the 12 food matrices, the average recoveries of the drugs ranged from 86.6% to 107.5% with relative standard deviations (RSDs) of 1.1%-10.9% ( n =6) at low, medium, and high spiked levels. Furthermore, this method was successfully applied to the analysis of real food samples. Overall, the newly developed method is simple, rapid, sensitive, accurate, and suitable for the qualitative and quantitative determination of antihypertensive drugs in different food matrices. This work could provide technical support for food safety agencies in implementing measures against the illegal addition of antihypertensive drugs to food.

The present work describes a developed analytical method based on a colorimetric assay using gold nanoparticles (AuNPs) along with chemometric techniques for the simultaneous estimation of sofosbuvir (SOF) and ledipasvir (LED) in their synthetic mixtures and tablet dosage form. The applied chemometric approaches were continuous wavelet transform (CWT) and least squares support vector machine (LS-SVM). Characterization of AuNPs and AuNPs in combination with the drug was performed by UV-vis spectrophotometer, transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared (FTIR) spectroscopy. In the CWT method, the zero amplitudes were determined at 427 nm with Daubechies wavelet family for SOF (zero crossing point of LED) and 440 nm with Symlet wavelet family for LED (zero crossing point of SOF) over the concentration range of 7.5-90.0 μg/L and 40.0-100.0 μg/L with coefficients of determination (R 2 ) of 0.9974 and 0.9907 for SOF and LED, respectively. The limit of detection (LOD) and limit of quantification (LOQ) of this method were found to be 7.92, 9.96 μg/L and 12.02, 30.2 μg/L for SOF and LED, respectively. In the LS-SVM model, the mean percentage recovery of SOF and LED in synthetic mixtures was 98.29 % and 99.25 % with root mean square error of 2.392 and 1.034, which were obtained by the optimization of regularization parameter (γ) and width of the function (σ) based on the cross-validation method. The proposed methods were also applied for the determination concentration of SOF and LED in the combined dosage form, recoveries were higher than 95 %, and relative standard deviation (RSD) values were lower than 0.4 %. The achieved results were statistically compared with those obtained from the high-performance liquid chromatography (HPLC) technique for the concurrent estimation of components through one-way analysis of variance (ANOVA), and no significant difference was found between the suggested approaches and the reference one. According to these results, simplicity, high speed, lack of time-consuming process, and cost savings are considerable benefits of colorimetry along with chemometrics methods compared to other ways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mizolastine is an antihistamine drug that is commonly used for treatment of chronic urticaria and allergic rhinitis. In this study, a facile, rapid, and sustainable fluorimetric method was established for the estimation of mizolastine in pharmaceutical and biological matrices for the first time. The approach methodology relied on the direct assessment of mizolastine's intrinsic fluorescence at 313 nm after excitation at 272 nm. This intrinsic fluorescence, stemming from the benzimidazole fluorophore moiety in mizolastine structure, serves as a distinctive marker for its precise quantification in the spiked human plasma and pharmaceutical formulations with high %recovery. The method exhibits reasonable sensitivity with lower limits of detection and quantification of 5.4 and 16.6 ng mL -1 , respectively, across a concentration range of 25.0-2000.0 and 50-1000 ng mL -1 for the standard mizolastine analysis and mizolastine assay in the plasma sample, respectively. Moreover, the established method was applied to assess tablet content uniformity and mizolastine assay in plasma samples with high recoveries (98.50%-100.20%). Such applications underscore the method's potential applicability within quality control laboratories, preventing the need for sample preparation or laborious extraction steps. Finally, the method's sustainability and practicality were confirmed by applying different greenness and whiteness metrics, yielding excellent results., (© 2024 John Wiley & Sons Ltd.)

High fluorescence intensity microspheres such as aggregation-induced emission fluorescence microspheres (AIEFM) have improved the sensitivity of lateral flow immunoassay (LFIA). The preparation of immune probes in LFIA usually adopts the chemical coupling strategy with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide for antibody coupling, which has the problems of low coupling efficiency, tedious coupling process, and poor repeatability. A biocompatible metal-phenolic network (MPN), which contains large amounts of phenols and galloyl groups, could easily, quickly, and stably couple with antibodies. Herein, we proposed a strategy based on MPN modification on ultrabright AIEFM surface as a novel label for the rapid detection of carbendazim. The limit of detection of AIEFM@MPN-LFIA was 0.019 ng/mL, which was 4.9 times lower than that of AIEFM-LFIA. In spiked samples, the average recoveries of AIEFM@MPN-LFIA ranged from 80% to 118% (coefficient of variation <13.45%). Therefore, AIEFM@MPN was a promising signal label that could improve the detection performance of LFIA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

For the first time the sensitive determination of carbendatim (CRB) is reported utilizing a well-designed sensing architecture based on vanadium diselenide-multiwalled carbon nanotube (VSMC). FTIR, XRD, FESEM, EDS, and EIS were employed to evaluate the sensor's structural integrity, and the results demonstrated the successful integration of nanomaterials, resulting in a robust and sensitive electrochemical sensor. Cyclic voltammetry (CV) and chronoamperometric (CA) investigations showed that the sensor best performed at pH 8.0 (BRB) with an excellent detection limit of 9.80 nM with a wide linear range of 0.1 to 10.0 µM. A more thermodynamically viable oxidation of CRB was observed at the VSMC/GCE, with a shift of 200 mV in peak potential towards the less positive side compared with the unmodified GCE. In addition, the sensor demonstrated facile heterogeneous electron transfer, favorable anti-fouling traits in the presence of a wide range of interferents, good stability, and reproducible analytical performance. Finally, the developed sensor was validated for real-time quantification of CRB from spiked water, food, and bio-samples, which depicted acceptable recoveries (98.6 to 101.5%) with RSD values between 0.35 and 2.23%. Further, to derive the possible sensing mechanism, the valence orbitals projected density of states (PDOS) for C, H, and N atoms of an isolated CRB molecule, VSe 2  + CNT and VSe 2  + CNT + CRB were calculated using density functional theory (DFT) calculations. The dominant charge transfer from the valence 2p-orbitals of the C and N atoms of CRB to CNT is responsible for the electrochemical sensing of CRB molecules., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

For the approval of a drug, the stability data must be submitted to regulatory authorities. Such analyses are often time-consuming and cost-intensive. Forced degradation studies are mainly carried out under harsh conditions in the dissolved state, often leading to extraneous degradation profiles for a solid drug. Oxidative mechanochemical degradation offers the possibility of generating realistic degradation profiles. In this study, a sustainable mechanochemical procedure is presented for the degradation of five active pharmaceutical ingredients (APIs) from the sartan family: losartan potassium, irbesartan, valsartan, olmesartan medoxomil, and telmisartan. High-resolution mass spectrometry enabled the detection of impurities already present in untreated APIs and allowed the elucidation of degradation products. Significant degradation profiles could already be obtained after 15-60 min of ball milling time. Many of the identified degradation products are described in the literature and pharmacopoeias, emphasizing the significance of our results and the applicability of this approach to predict degradation profiles for drugs in the solid state.

The emergence of 2-benzylbenzimidazole "nitazene" opioids is stirring up the recreational synthetic opioid market. Many nitazene analogues act as potent agonists at the µ‑opioid receptor (MOR), as demonstrated in various in vitro and in vivo studies. Severe intoxication and overdose deaths associated with nitazene analogues are increasingly being reported. Nitazene opioids are classified as a public health threat, stressing the need for close monitoring of new developments on the recreational drug market. This study reports on the detection of N-desethyl etonitazene in a sample handed in by a recreational drug user at a Swiss drug checking service in August 2023. The person bought the sample through an internet source where it was stated to contain isotonitazene. Chemical analyses were conducted to characterize the sample, i.e. nuclear magnetic resonance (NMR), capillary electrophoresis (CE), and high-resolution mass spectrometry (HRMS). The sample was additionally investigated using two different in vitro MOR activation assays. NMR and high-performance liquid chromatography (HPLC) coupled to HRMS confirmed the presence of N-desethyl etonitazene at a high purity and in the absence of isotonitazene and etonitazene. N-Desethyl nitazene analogues have been detected before as metabolites of isotonitazene and etonitazene. However, as first seen with N-desethyl isotonitazene, they are now emerging as standalone drugs. The applied bioassays demonstrated increased efficacy and approximately 6-9-fold higher potency of N-desethyl etonitazene at MOR compared to fentanyl. N-Desethyl etonitazene showed EC 50 values of 3.35 nM and 0.500 nM in the β-arrestin 2 recruitment and Aequoscreen® assays, respectively. The opioid activity present in the collected sample was additionally evaluated using the bioassays and showed good overlap with the reference standard, in line with the analytical purity assessment. This demonstrates the potential of these bioassays to provide a rapid opioid activity assessment of authentic samples. The emergence of other N-desethyl nitazene analogues must be considered during forensic and clinical toxicology casework, to avoid misclassification of intake of such analogues as metabolites. Finally, drug checking services enable the close monitoring of market developments and trends and are of great value for early warning and harm reduction purposes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

It is highly desirable to develop a low-cost and rapid detection method for trace levels of carbendazim fungicide residues, which would be beneficial for improving human health and mitigating environmental issues. Herein, isolated single tungsten atoms were implanted onto well-organized metal-organic framework (MOF)-derived N-doped carbons to form W-N-C single-site heterojunctions with ultrahigh electrocatalytic activity. The coupling of W-N-C with Cu 3 (HHTP) 2 , an electronically conductive MOF with a large surface area and porous structure, exhibited enhanced electrocatalytic performance for the oxidation of carbendazim (CBZ) when they were used for decorating graphene nanoplatelet flexible electrode arrays fabricated via template-assisted scalable filtration. A wide linear range (3.0 nM-50 μM) with an ultra-low detection limit of 0.97 nM and fast response was achieved for CBZ analysis. Moreover, the sensing platform has been utilised to monitor CBZ levels in vegetable samples with satisfactory recovery rates of 97.2-102% and a low relative standard deviation of 1.9%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rationale: With the development of matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry (MS) in spatial localisation omics research on small molecules, the detection sensitivity of the matrix must increase. However, the types of matrices suitable for detecting acidic small molecules in (-) MALDI-MS mode are very limited and are either not sensitive enough or difficult to obtain., Methods: More than 10 commercially available benzimidazole and benzothiazole derivatives were selected as MALDI matrices in negative ion mode. MALDI-MS analysis was performed on 38 acidic small molecules and mouse serum, and the matrix effects were compared with those of the common commercial matrices 9-aminoacridine (9AA), 1,5-naphthalenediamine (DAN) and 3-aminoquinoline (3AQ). Moreover, the proton affinity (PA) of the selected potential matrix was calculated, and the relationships among the compound structure, PA value and matrix effect were discussed., Results: In (-) MALDI-MS mode, a higher PA value generally indicates a better matrix effect. Amino-substituted 2-phenyl-1H-benzo[d]imidazole derivatives had well-defined matrix effects on all analytes and were generally superior to the commonly used matrices 9AA, DAN and 3AQ. Among them, 2-(4-(dimethylamino-phenyl)-1H-benzo[d]imidazole-5-amine (E-4) has the best sensitivity and versatility for detecting different analytes and has the best ability to detect fatty acids in mouse serum; moreover, the limit of detection (LOD) of some analytes can reach as low as ng/L., Conclusions: Compared to 9AA, DAN and 3AQ, matrix E-4 is more effective at detecting low-molecular-weight acidic compounds in (-) MALDI-MS mode, with higher sensitivity and better versatility. In addition, there is a clear correlation between compound structure, PA and matrix effects, which provides a basis for designing more efficient matrices., (© 2024 John Wiley & Sons Ltd.)

2-Benzylbenzimidazoles, or "nitazenes", are a class of novel synthetic opioids (NSOs) that are increasingly being detected alongside fentanyl analogs and other opioids in drug overdose cases. Nitazenes can be 20× more potent than fentanyl but are not routinely tested for during postmortem or clinical toxicology drug screens; thus, their prevalence in drug overdose cases may be under-reported. Traditional analytical workflows utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) often require additional confirmation with authentic reference standards to identify a novel nitazene. However, additional analytical measurements with ion mobility spectrometry (IMS) may provide a path toward reference-free identification, which would greatly accelerate NSO identification rates in toxicology laboratories. Presented here are the first IMS and collision cross section (CCS) measurements on a set of fourteen nitazene analogs using a structures for lossless ion manipulations (SLIM)-orbitrap MS. All nitazenes exhibited two high intensity baseline-separated IMS distributions, which fentanyls and other drug and druglike compounds also exhibit. Incorporating water into the electrospray ionization (ESI) solution caused the intensities of the higher mobility IMS distributions to increase and the intensities of the lower mobility IMS distributions to decrease. Nitazenes lacking a nitro group at the R1 position exhibited the greatest shifts in signal intensities due to water. Furthermore, IMS-MS/MS experiments showed that the higher mobility IMS distributions of all nitazenes possessing a triethylamine group produced fragment ions with m / z 72, 100, and other low intensity fragments while the lower mobility IMS distributions only produced fragment ions with m / z 72 and 100. The IMS, solvent, and fragmentation studies provide experimental evidence that nitazenes potentially exhibit three gas-phase protomers. The cyclic IMS capability of SLIM was also employed to partially resolve four sets of structurally similar nitazene isomers (e.g., protonitazene/isotonitazene, butonitazene/isobutonitazene/secbutonitazene), showcasing the potential of using high-resolution IMS separations in MS-based workflows for reference-free identification of emerging nitazenes and other NSOs.

Agricultural products are vitally important for sustaining life on earth and their production has notably grown over the years worldwide in general and in Brazil particularly. Elevating agricultural practices consequently leads to a proportionate increase in the usage of pesticides that are crucially important for enhanced crop yield and protection. These compounds have been employed excessively in alarming concentrations, causing the contamination of soil, water, and air. Additionally, they pose serious threats to human health. The current study introduces an innovative tool for producing appropriate materials coupled with an electrochemical sensor designed to measure carbendazim levels. The sensor is developed using a molecularly imprinted polymer (MIP) mounted on a glassy carbon electrode. This electrode is equipped with multi-walled carbon nanotubes (MWCNTs) for improved performance. The combined system demonstrates promising potential for accurately quantifying carbendazim. The morphological characteristics of the synthesized materials were investigated using field emission scanning electron microscopy (FESEM) and the Fourier-transform infrared (FTIR) technique. The analytical curve was drawn using the electrochemical method in the range of 2 to 20 ppm while for HPLC 2-12 ppm; the results are presented as the maximum adsorption capacity of the MIP (82.4%) when compared with NIP (41%) using the HPLC method. The analysis conducted using differential pulse voltammetry (DPV) yielded a limit of detection (LOD) of 1.0 ppm and a repeatability of 5.08% ( n = 10). The results obtained from the analysis of selectivity demonstrated that the proposed electrochemical sensor is remarkably efficient for the quantitative assessment of carbendazim, even in the presence of another interferent. The sensor was successfully tested for river water samples for carbendazim detection, and recovery rates ranging from 94 to 101% were obtained for HPLC and 94 to 104% for the electrochemical method. The results obtained show that the proposed electrochemical technique is viable for the application and quantitative determination of carbendazim in any medium.

Pesticides are considered one of the main sources of contamination of surface waters, especially in rural areas highly influenced by traditional agricultural practices. The objective of this work was to evaluate the impact caused by pesticides and their transformation products (TPs) related to olive groves in surface waters with strong agricultural pressure. 11 streams were monitored during four sampling campaigns over 2 years. A solid-phase extraction, followed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) analysis was used in the quantitative target approach, with more than 70 validated compounds. Target method was combined with a suspect screening strategy involving more than 500 pesticides and TPs, using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) to identify additional pesticides and TPs out of the scope of analysis. A total of 43 different compounds were detected with the target method. The herbicide MCPA was present in all samples and at the highest concentration (1260 ng L -1 ), followed by the fungicide carbendazim (1110 ng L -1 ), and the herbicide chlorotoluron (706 ng L -1 ). The suspect screening strategy revealed the presence of 7 compounds out of the target analysis (1 pesticide and 6 TPs). 6 analytes were confirmed with the analytical standards. Semi-quantification results revealed that TPs exhibited higher concentrations than their corresponding parent compounds, indicating higher persistency. Some small streams showed a comparable number of pesticides and concentrations to the most polluted large river. The determined pesticide and TPs concentrations represented an estimated environmental hazard in almost all sampling sites under study. This work underscores the importance of including pesticide TPs and small streams impacted by extensive agricultural activities in water quality monitoring programs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study, surface-enhanced Raman spectroscopy (SERS) combined with chemometric methods were developed for qualitative and quantitative analysis of four benzimidazole (BMZs) residues in corn. Sulfhydryl functionalized Fe 3 O 4 @SiO 2 @Ag-SH magnetic SERS substrates were prepared to obtain the SERS spectra of four BMZs for chemometric analysis. The partial least squares regression discrimination analysis (PLS-DA) model performed best, with a recall rate upwards 99.17%, and could successfully distinguish four BMZs. Under the support vector machine regression (SVR) model, the detection limits of carbendazim, benomyl, thiophanate-methyl and thiabendazole were 0.055 mg/L, 0.056 mg/L, 0.067 mg/L and 0.093 mg/L, respectively; the average recovery was in the range of 85.6%-107.5%. Furthermore, the method verified by HPLC, and the results showed that there was no significant difference between two methods (p > 0.05). Therefore, the strategy based on SERS coupling chemometrics can be served as a promising tool for rapid determination of BMZs residues in food., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this work, a four-way multivariate calibration method for the simultaneous determination of four pesticides - carbendazim (CBZ), thiabendazole (TBZ), pirimiphos-methyl (PMM), and clothianidin (CLT) - in lemon juice is presented. Third-order data were acquired by registering the photoinduced fluorescence of the analytes as excitation-emission matrices at different times of UV-light irradiation, in the presence of organized media (direct micelles) as fluorescence enhancers. The optimal experimental conditions (pH 11.5 and 32 mmol L -1 hexadecyltrimethylammonium chloride surfactant) were determined through a central composite design using the response surface methodology. The analytes were individually calibrated, except for TBZ and CBZ due to the inner filter effect of TBZ on CBZ. Test samples containing all analytes and imidacloprid (as potential interference) were analysed. PARAFAC was utilized to evaluate both the trilinearity and quadrilinearity of the third-order data and four-way arrays, respectively. PMM was successfully determined with quadrilinear PARAFAC decomposition, whereas CLT, TBZ, and CBZ were satisfactorily modelled using U-PLS/RTL due to the loss of quadrilinearity caused by different phenomena. The profitable applicability of the analytical method in the CBZ, TBZ, PMM, and CLT determination in lemon juice samples was demonstrated, achieving limits of detection below the maximum residue levels reported by the European Commission, and mean recoveries at 90 ± 5%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Carbendazim is a broad-spectrum systemic fungicide that is used to control various fungal diseases in agriculture, horticulture, and forestry. Carbendazim is also used in post-harvest applications to prevent fungal growth on fruits and vegetables during storage and transportation. Carbendazim is regulated in many countries and banned in others, thus, there is a need for the sensing of carbendazim to ensure that high levels are avoided which can result in potential health risks. One approach is the use of electroanalytical sensors which present a rapid, but highly selective and sensitive output, whilst being economical and providing portable sensing platforms to support on-site analysis. In this minireview, we report on the electroanalytical sensing of carbendazim overviewing recent advances, helping to elucidate the electrochemical mechanism and provide conclusions and future perspectives of this field.

Background: Flibanserin (FLB) was first synthesized as an antidepressant drug; however, due to its enhancing effects on sexual activity, it was approved for treatment of hypoactive sexual desire disorder in women in 2015., Objective: The aim of this study was to develop a new and fully validated HPLC method for analysis of FLB in pharmaceutical formulations besides its degradation products, and identification of possible formation mechanisms by using HPLC-DAD-ESI-IT-TOF-MSn., Method: The HPLC separation was achieved in a Supelco Ascentis® Express series phenyl hexyl column (100 × 4.6 mm, ID 2.7 µm). The mobile phase was acetonitrile-ammonium acetate solution (50:50, v/v, 10 mM, pH 5.4) mixture, which was pumped at the rate of 0.5 mL/min. Chromatography, detection, and structural identification was performed by using a LCMS-IT-TOF instrument (Shimadzu, Japan)., Results: 1-(2-(4-(3-hydroxy-5-(trifluoromethyl)phenyl)piperazine-1-yl)ethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one is proposed as a novel degradation product, with a mass of 407.1695 and a formula of C20H21F3N4O2 with a margin of error about 0.001 ppm. The developed method is applicable with 98% accuracy within the 2.5-50.0 µg/mL range. The LOD and LOQ were about 500 ng/mL and 1.50 µg/mL, respectively. The transferability and variation between laboratories were tested by inter-laboratory comparison and evaluated with one-way analysis of variance., Conclusions: A novel FLB degradation product, which was produced under oxidative forced degradation conditions was observed and identified for the first time; in addition, the formation kinetics of the degradation product besides decomposition of FLB was studied. Furthermore, an inter-laboratory comparison was carried out, and application of the proposed method on a pseudo Addyi® (Sprout Pharmaceuticals, Inc.) sample was tested using both instrument configurations., Highlights: A novel stability-indicating assay method was developed and fully validated according to the International Council on Harmonization (Q2) R1 for the analysis of FLB in the pharmaceutical preparations. A new degradation product was identified in the oxidative forced degradation condition and characterized using HPLC-DAD-ESI-IT-TOF-MS3. Moreover, the possible mechanism and the formation kinetic of the degradation product were revealed. In addition, the developed method was transferred to another LC-PDA instrument for inter-laboratory comparison. Finally, the current method was applied to a pseudo formulation of Addy in both instruments, and ANOVA was applied for evaluation., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Dielectric barrier discharge (DBD) cold plasma, as a new nonthermal technology, has attracted increasing attention in pesticide degradation. In this study, DBD plasma was used to degrade carbendazim (MBC) in aqueous solution. Under the optimal conditions (160 kv, 50 Hz), MBC solution (0.5 μg/mL) was degraded by 89.04% after plasma treatment for 10 min. Four MBC degradation products were identified, one of which was a common oxidative degradation product (5-hydroxycarbendazim, m/z 208.07); the others were identified (m/z 118.06, m/z 132.08 and m/z 104.05) to have formed by the cleavage of the benzimidazole heterocyclic ring. The degradation pathways were obtained by analysis of degradation products at different treatment times. The toxicity of the degradation products was estimated based on the survival rate of yeast, indicating much lower toxicity levels compared to that of MBC. This study provides a theoretical basis for the application of DBD plasma in the degradation of benzimidazole pesticides in foods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Natural products continue to be a valuable source of active metabolites; however, researchers of natural products are mostly focused on the biological effects, and their chemical utility has been less explored. Furthermore, low throughput is a bottleneck for classical natural product research. In this work, a new offline HPLC/CC/SCD (high performance liquid chromatography followed by co-crystallization and single crystal diffraction) workflow was developed that greatly expedites the discovery of active compounds from crude natural product extracts. The photoactive total alkaloids of the herbal medicine Coptidis rhizome were firstly separated by HPLC, and the individual peaks were collected. A suitable coformer was screened by adding it to the individual peak solution and observing the precipitation, which was then redissolved and used for co-crystallization. Seven new co-crystals were obtained, and all the single crystals were subjected to X-ray diffraction analysis. The molecular structures of seven alkaloids from milligrams of crude extract were resolved within three days. NDS greatly decreases the required crystallization amounts of alkaloids to the nanoscale and enables rapid stoichiometric inclusion of all the major alkaloids with full occupancy, typically without disorder, affording well-refined structures. It is noteworthy that anomalous scattering by the coformer sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. Moreover, the identified alkaloids were firstly found to be photocatalysts for the green synthesis of benzimidazoles. This study demonstrates a new and green phytochemical workflow that can greatly accelerate natural product discovery from complex samples.

A quantitative multi-class multi-residue analytical method was developed for the determination of veterinary drugs in milk by high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). A total of 132 veterinary drugs investigated belonged to almost 15 classes including sulfonamides, β-lactams, tetracyclines, quinolones, macrolides, nitrofurans, nitroimidazoles, phenicols, lincosamides, pleuromutilins, macrocyclic lactones, quinoxaline antibiotics, benzimidazoles, anthelmintics, coccidiostats and some others. A magnetic solid-phase extraction procedure was developed using magnetic hypercrosslinked polystyrene (HCP/Fe 3 O 4 ) for the sample preparation prior to HPLC-MS/MS without deproteinization step. The results indicated recoveries of 85-107% for 14 sulfonamides, 85-120% for 13 β-lactams, 89-115% for 4 tetracyclines, 82-119% for 14 quinolones, 82-115% for 8 macrolides, 97-109% for 4 nitrofurans, 84-115% for 10 nitroimidazoles, 89-114% for 3 phenicols, 86-111% for 3 lincosamides, 97-102% for 2 pleuromutilins, 72-88% for 4 macrocyclic lactones, 87-104% for 4 quinoxaline antibiotics, 76-119% for 21 benzimidazoles, 79-115% for 12 anthelmintics, 81-118% for 12 coccidiostats and 75-119 % for 5 unclassified drugs, with relative standard deviations (RSDs) of less than 20%, and the LOQs ranged from 0.05 to 1 μg kg -1 . This methodology was then applied to field-collected real milk samples and trace levels of some veterinary drugs were detected., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, a platinum-doped nickel cobaltite nanograss (Pt-doped NiCo 2 O 4 NG) with its own unique structural features was initially synthesized, utilizing a simple hydrothermal method and then applied as a novel platform for the detection of carbendazim (C 9 H 9 N 3 O 2 ; CBZ). To this end, the CBZ electrochemical signals were evaluated by means of differential pulse voltammetry (DPV), demonstrating the acceptable catalytic effect of the Pt-doped NiCo 2 O 4 NG/screen-printed electrode (SPE) on the CBZ oxidation signal. Under the optimized conditions, CBZ was subsequently quantified by the Pt-doped NiCo 2 O 4 NG/SPE with a wide linear range (0.03-140 μM) and a low limit of detection (LOD) value (0.005 μM). The proposed sensor was thus characterized by good anti-interference ability, selectivity, and stability. The analysis of the real samples, viz. tomato and lettuce, also confirmed that the given sensor had good recoveries and relative standard deviation (RSD). Ultimately, a comparison between liquid chromatography-mass spectrometry (LC-MS) and this method established no significant difference in the results., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The current detection method of carbendazim suffers from the disadvantages of complicated preprocessing and long cycle time. In order to solve the problem of rapid quantitative screening of finite contaminants, this article proposed a qualitative method based on characteristic peaks and a semi-quantitative method based on threshold to detect carbendazim in apple, and finally the method is evaluated by a validation system based on binary output. The results showed that the detection limit for carbendazim was 0.5 mg/kg, and the detection probability was 100% when the concentration was no less than 1 mg/kg. The semi-quantitative analysis method had a false positive rate of 0% and 5% at 0.5 mg/kg and 2.5 mg/kg, respectively. The results of method evaluation showed that when the added concentration was greater than 2.5 mg/kg, the qualitative detection method was consistent with the reference method. When the concentration was no less than 5 mg/kg, the semi-quantitative method is consistent between different labs. The semi-quantitative method proposed in this study can achieve the screening of finite contaminants in blind samples and simplify the test validation process through the detection probability model, which can meet the needs of rapid on-site detection and has a good application prospect.

Carbendazim (CBZ) has been widely used in agricultural production to control fruits and vegetables diseases, but it can also destroy the human endocrine system. Therefore, sensitive detection of CBZ has attracted increasing attention worldwide. In this study, Pd nanoparticles (Pd NPs) decorated on CdS microsphere (Pd NPs/CdS) was prepared by the in-situ photoreduced method, and based on the surface plasmon resonance (SPR) effect of noble metal and Schottky junction between Pd nanoparticles (Pd NPs) and CdS microsphere, the photocurrent after introducing Pd NPs is 7.7 times higher than that of bare CdS microsphere. In view of the outstanding photoelectrochemical (PEC) performance of Pd NPs/CdS and the high specificity of the aptamer, the as-fabricated PEC aptasensor for CBZ detection possesses the excellent detection performance including a broad linear ranging from 1.0 × 10 -12 to 1.0 × 10 -6  mol/L as a low detection limit of 3.3 × 10 -13  mol/L (S/N = 3). Furthermore, the PEC aptasensor was used for determination of lettuce samples from actual agricultural products with satisfactory results., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A rapid, selective, and sensitive method was developed for the detection of carbendazim and thiabendazole in edible vegetable oil. Two benzimidazole analytes were pre-concentrated by magnetic solid phase extraction (MSPE) using flowerlike Ni-NiO composite as sorbents and followed by LC-MS/MS analysis. The flowerlike Ni-NiO composite sorbent displayed a high affinity towards benzimidazole analytes due to the reversible coordination interaction between the Ni(Ⅱ) ion and the electron-donating imidazole group. In comparison to the previous methods, this procedure is less time-consuming and simpler during sample preparation. The parameters affecting the extraction efficiency were optimized in detail. The method was validated according to SANTE/12682/2019. The limits of detection were in the range of 0.001-0.003 mg•kg -1 . The recoveries ranged from 89.3% to 110.7% with inter-day and inter-day precision less than 10.9%. The results indicate that flowerlike Ni-NiO composite might be a promising alternative for MSPE of benzimidazole compounds in foods., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A specific and sensitive thin layer chromatographic method coupled with fluorescence detection for determination of flibanserin (FLN) that treats woman hypoactive sexual desire disorder was developed. The proposed method depends on the enhancement of FLN native fluorescence intensity via the exposure of the developed TLC plate to concentrated hydrochloric acid vapors. Herein, an evaporation setup needed for HCl vapors exposure step was designed for the first time to ensure a uniform distribution of the vapors throughout the developed bands on the plate. Chloroform: methanol (9.5: 0.5, v/v) was the optimum mobile phase that gave a compact band (R f = 0.44 ± 0.02) using TLC aluminium plates precoated with silica gel G 60F 254 as a stationary phase. After exposure of the developed TLC plate to HCl vapors, the FLN bands emission intensities were measured after excitation at 275 nm. Conferring ICH guidelines, the linearity range was 20.0 - 1500.0 ng/band with a good linear relationship (r= 0.9998). Detection and quantitation limits were 5.12 and 15.50 ng/band, respectively. Also, the method was validated for accuracy, precision, robustness, specificity and selectivity. Statistical analysis verified the suitability of the proposed method for estimation of FLN in tablets and in human plasma with acceptable recoveries (98.07-101.45%)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Helminth infections in animals to be consumed by humans are an important medical and public health problem. Pharmaceutical research has focused on developing new anthelmintic drugs for parasite control in these animals. However, the incorrect use of anthelmintics can leave residues in animal products intended for human consumption. Their determination is therefore crucial in terms of food safety., Results: In this work, a simple and sensitive method has been developed for the analysis of anthelmintic drugs in milk. The method involves extraction of the analytes using a QuEChERS (quick, easy, cheap, effective, rugged, and safe) method, and separation and determination by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The use of a core-shell column significantly reduced the analysis time compared with conventional columns. The method was validated and applied to the analysis of different commercial milk samples: whole, semi-skimmed and skimmed cows' milk, and goats' milk. None of the benzimidazoles studied was found in the samples analyzed, so these were spiked with the analytes at three concentration levels (10, 50, and 100 μg kg -1 )., Conclusions: The proposed method provided high sensitivity compared with other methods for the determination of anthelmintics in milk samples, at concentration levels well below the established maximum residue limit (MRLs) values. The proposed method is simple, easy, precise, accurate, and leads to good recovery levels. It can be used successfully for the routine analysis. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

A new method involving matrix solid-phase dispersion (MSPD) and dispersive liquid-liquid microextraction (DLLME) was optimized with the aid of stoichiometry and applied to the extraction, purification, and determination of benzimidazole residues in vegetables. Carbendazim, thiabendazole, and thiophanate-methyl were selectively extracted from vegetables using cucurbit[7]uril as the MSPD extractant and transferred to an aqueous solution, then further enriched using DLLME with acetonitrile and chloroform as dispersive and extraction solvents, respectively. The optimal extraction conditions of MSPD and DLLME were selected by two-level full-factorial design and central-composite design (CCD). The developed method (MSPD-DLLME-HPLC-UV) showed good linearity in the range of 0.025-5 μg/g, with R 2 > 0.9984. Intra- and interday precisions were 5.3-10.9% and 10.6-12.4%, respectively, and the limit of detection was between 0.004 and 0.007 μg/g of fresh weight. This method was applied to the analysis of four different types of vegetables, and the recoveries ranged from 65.4% to 124.0%. The method was environmentally friendly, easy to operate, and sensitive., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this paper, a novel ratiometric electrochemical sensor for carbendazim (CBZ) detection was constructed by a composite of MXene@Ag nanoclusters and amino-functionalized multi-walled carbon nanotubes (MXene@AgNCs/NH 2 -MWCNTs). The Ag nanoclusters (AgNCs) embedded in the MXene not only could inhibit the aggregation of MXene flakes and enhance the electrocatalytic ability, but also serve as an internal reference probe for the ratiometric electrochemical detection. Moreover, the introduction of NH 2 -MWCNTs can further improve the electrochemical signals of CBZ and Ag, resulting in the enhanced signal amplification and higher sensitivity. Based on these characteristics of the MXene@AgNCs/NH 2 -MWCNTs composite, the proposed sensor exhibits a favorable linear relationship between I CBZ /I AgNCs and the concentration of CBZ ranging from 0.3 nM to 10 μM and a low limit of detection of 0.1 nM. Moreover, the proposed ratiometric electrochemical sensing platform also demonstrates high selectivity, good reproducibility, secular stability, and satisfactory applicability in vegetable samples., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Traditionally in Korea, Protaetia brevitarsis seulensis (white-spotted flower chafer) has been used as a medicine, and recently has attracted increased attention due to its antithrombotic efficacy. Some of spent mushroom compost or fermented oak sawdust, a feedstock for P. brevitarsis, were contaminated with three fungicides, carbendazim, dimethomorph, and fenoxanil, which could be transferred to the insect. This study was aimed to optimize a simple extraction method combined with liquid chromatography tandem mass spectrometry and apply it to the real samples. After the pulverized samples (5 g) were extracted with acetonitrile (10 mL) and formic acid (100 μL), fat and lipids in the samples were slowly precipitated at -20°C for 24 hours. After eight different clean-up methods were investigated, the mixture of 150 mg MgSO4/25 mg PSA/25 mg C18 was selected due to optimal recovery of the target compounds. Recovery (77.9%‒80.8% for carbendazim, 111.2%‒116.7% for dimethomorph, and 111.9%‒112.5% for fenoxanil) was achieved with reasonable relative standard deviation (<5.5%) The analytical method developed in this study was used to analyze three compounds in the 24 insect samples donated by the insect farm owners but no target compounds were detected. These results can provide important data for establishing the pesticide safety standards for P. brevitarsis before the medical applications., Competing Interests: The authors have declared that no competing interests exist.

Background: Thiophanate-methyl and its metabolite carbendazim are broad-spectrum fungicides used on many crops. The residues of these chemicals could result in potential environmental and human health problems. Therefore, investigations of the dissipation and residue behaviors of thiophanate-methyl and its metabolite carbendazim on cowpeas and associated dietary risk assessments are essential for the safety of agricultural products., Results: A simple analytical approach using liquid chromatography with tandem mass spectrometry was developed and validated for the determination of thiophanate-methyl and carbendazim concentrations in cowpeas. Good linearity (R 2  > 0.998) was obtained, and the recoveries and relative standard deviations were 80.0-104.7% and 1.4-5.2%, respectively. The dissipation rates of thiophanate-methyl, carbendazim and total carbendazim were high (half-lives of 1.61-2.46 days) and varied in the field cowpea samples because of the different weather conditions and planting patterns. Based on the definition of thiophanate-methyl, the terminal residues of total carbendazim in cowpea samples were below the maximum residue limits set by Japan for other legumes. The acute and chronic risk quotients of three analytes were 0.0-27.6% in cowpea samples gathered from all terminal residue treatments, which were below 100%., Conclusion: An optimized approach for detecting thiophanate-methyl and carbendazim in cowpeas was applied for the investigation of field-trial samples. The potential acute and chronic dietary risks of thiophanate-methyl, carbendazim and total carbendazim to the health of Chinese consumers were low. These results could guide the safe and proper use of thiophanate-methyl in cowpeas and offer data for the dietary risk assessment of thiophanate-methyl in cowpeas. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Hepatitis C virus (HCV) is an infectious disease that has become a global clinical issue because of its significant morbidity and mortality. Novel anti-hepatitis C drugs are continuously developed to decrease the pervasiveness of the infection globally. A synthetic ravidasvir, benzimidazole-naphthylene-imidazole derivatives, has been used as an anti-HCV drug. This study determined the metabolites of ravidasvir and its pharmacokinetics in rats using information-dependent acquisition and multiple reaction monitoring scanning modes in linear ion trap LC-MS/MS instrument, respectively. Two time-programming linear-gradient chromatographic methods were employed using a Kinetex C 18 column (50 × 3 mm, 2.6 μm) and a Luna HILIC column (100 × 4.6 mm, 3 μm) for the qualitative and quantitative determination of ravidasvir and its metabolites, respectively. In silico prediction where sites in a molecule are susceptible to metabolism by cytochrome P 450 was implemented, which helped in proposing the metabolic pathway of ravidasvir. The most dominant metabolite in rat liver microsomal samples was oxidative ravidasvir, where one O-demethylated metabolite and eight isomers of the oxidative ravidasvir metabolites were identified. The study provides essential data for proposing the metabolic pathway and successfully applied it to determine the pharmacokinetics of ravidasvir in rat plasma., (© 2021 John Wiley & Sons, Ltd.)

This paper reports on the identification and full chemical characterization of the substance colloquially called "etonitazepyne" or "N-pyrrolidino etonitazene" (2-(4-ethoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzo[d]imidazole), a potent NPS opioid of the 5-nitrobenzimidazole class. Identification of etonitazepyne was performed, on a sample purchased during routine monitoring of the drug market, using GC-MS, HRAM LC-MS/MS, 1 H NMR, and FTIR. The chromatographic data, together with the FTIR data, indicated the presence of a highly pure compound and already indicated a benzimidazole structure. The specific benzimidazole regio-isomer was confirmed using 1 H NMR spectroscopy, resulting in the unambiguous identification of etonitazepyne., (© 2021 John Wiley & Sons, Ltd.)

A method for simultaneous determination of carbendazim and tebuconazole residues in cabbage was developed and validated in LC-MS/MS. Samples were extracted and purified following the modified QuEChERS procedure, which enabled the elution of carbendazim and tebuconazole at 0.96 and 5.31 min, respectively. LOD and LOQ were 0.0005 and 0.0015 mg kg -1 , respectively. Mean recovery was in the range of 78.94 to 104.89% for carbendazim and 76.07 to 98.62% for tebuconazole. The field samples recorded residues of 0.274 and 0.481 mg kg -1 ; and 0.194 and 0.392 mg kg -1 at single and double dose for carbendazim and tebuconazole, respectively. Half-life values were 2.17 and 2.99 for carbendazim and 2.74 and 2.81 for tebuconazole at single and double dose, respectively. Decontamination with saltwater wash followed by cooking and lemon water wash found superior in the removal of residues more than 90%., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The dissipation behaviors and exposure risks of individual and joint application of procymidone and carbendazim in greenhouse strawberries were studied. The initial concentrations were similar after individual or joint applications, while the dissipation half-lives and finial concentrations were significantly different. After joint application, the dissipation half-lives of procymidone and carbendazim were 12.9 and 16.0 days, respectively, which were about 1.8 times higher than those after individual application. Furthermore, the final residues under joint application condition were 1.8-3.5 times higher than those under individual application condition. The joint application decreased the dissipation rates of procymidone or carbendazim in strawberries, and increased the final residue concentrations. The dietary intake risks of procymidone and carbendazim (whether applied individually or jointly) were no higher than 0.12, which were acceptable for human health. This work would shed a light for the guidance of the joint application and risk assessment of the typical fungicides in strawberry., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An aptasensor for electrochemical detection of carbendazim is reported with mulberry fruit-like gold nanocrystal (MF-Au)/multiple graphene aerogel (MGA) and DNA cycle amplification. HAuCl 4 was reduced by ascorbic acid in a CTAC solution containing KBr and KI and formed trioctahedron gold nanocrystal. The gold nanocrystal underwent structural evolution under enantioselective direction of L-cysteine. The resulting MF-Au shows a mulberry fruit-like nanostructure composed of gold nanocrystals of about 200 nm as the core and many irregular gold nanoparticles of about 30 nm as the shell. The exposure of high-index facets improves the catalytic activity of MF-Au. MF-Au/MGA was used for the construction of an aptasensor for electrochemical detection of carbendazim. The aptamer hybridizes with assistant strand DNA to form duplex DNA. Carbendazim binds with the formed duplex DNA to release assistant strand DNA, triggering one three-cascade DNA cycle. The utilization of a DNA cycle allows one carbendazim molecule to bring many methylene blue-labeled DNA fragments to the electrode surface. This promotes significant signal amplification due to the redox reaction of methylene blue. The detection signal is further enhanced by the catalysis of MF-Au and MGA towards the redox of methylene blue. A differential pulse voltammetric signal, best measured at - 0.32 V vs. Ag/AgCl, increases linearly with the carbendazim concentration ranging from 1.0 × 10 -16 to 1.0 × 10 -11  M with a detection limit of 4.4 × 10 -17  M. The method provides ultrahigh sensitivity and selectivity and was successfully applied to the electrochemical detection of carbendazim in cucumber. This study reports on an ultrasensitive aptasensor for electrochemical detection of carbendazim in cucumber based on mulberry fruit-like gold nanocrystal-multiple graphene aerogel and DNA cycle double amplification., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The detection of carbendazim (CBZ) is important for food safety and human health. However, most current analytical methods require large instruments and highly trained operators. In order to solve this problem, herein, an innovative portable and quantitative photothermal assay platform relying on a thermometer readout for the detection of CBZ has been developed. Gold nanoparticles (AuNPs), which exhibit a strong distance-dependent photothermal effect under specific laser irradiation, were utilized as indicators. The CBZ aptamer was introduced to protect AuNPs from salt-mediated aggregation. When CBZ is present, the binding event between CBZ and aptamer leads to the loss of the aptamer protective effect on AuNPs, and AuNP aggregation occurs. Under 650-nm laser irradiation, the increase in temperature associated with an AuNP-dependent photothermal effect is highly related to the CBZ concentration. Having the advantages of user-friendliness, low cost, quick response, and portability, this method has great potential for on-site applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The highly selective and sensitive electrochemical detection of highly toxic fungicide carbendazim (CBZ) by the iron (Fe)-doped copper vanadate (CuVO 4 ; CuV) is discussed. The Fe-doped copper vanadate (Fe-CuV) is prepared by the simple co-precipitation method followed by an annealing process which produced high crystallinity. The material properties of Fe-CuV are characterized by XRD, Raman spectrometry, XPS analysis, HRTEM, and SAED pattern. The electrochemical characterization of Fe-CuV towards CBZ detection are done by CV and DPV techniques. The Fe-CuV/GCE exhibits good electroanalytical activity towards the electro-oxidation of CBZ at the potential of 0.81 V vs Ag/AgCl. The developed sensor electrode revealed a linear range of 0.01 to 83.1 μM and a limit of detection of about 5 nM. In addition, Fe-CuV/GCE reveals good storage stability (RSD = 2.63%) and reproducibility (RSD = 2.85%) for the electro-oxidation of CBZ. The electrode material was applied to the detection of CBZ in apple juice and soy milk samples, and the results were discussed. Thus, our projected Fe-CuV/GCE can be employed as electrode material in a rapid onsite sensor for the detection and determination of noxious pollutants., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Carbendazim (CBZ) pesticide residues in food products have become a growing concern in recent years. Herein, a sensitive biosensor for detecting CBZ was developed based on luminescent resonance energy transfer (LRET) from aptamer labeled upconversion nanoparticles (UCNPs, donor) to manganese dioxide (MnO 2 , acceptor) nanosheets. The strong overlap between the absorption spectrum of MnO 2 and the UCNPs fluorescence emission allowed the luminescence quenching. With the addition of CBZ, it tended to bind with specific aptamers, which culminated in the UCNPs-aptamer dropping off MnO 2 nanosheets and restoring the fluorescence. A linear calibration plot between logarithmic CBZ concentration and fluorescence intensity was acquired in the range of 0.1-5000 ng·mL -1 , with a limit of detection 0.05 ng·mL -1 , indicating that the UCNPs- MnO 2 aptasensor is a rapid, sensitive and specific quantitative detection platform for CBZ. Furthermore, the precision and accuracy of the developed LRET biosensor was validated by HPLC method with no significant differences., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An innovative thin-layer chromatography method coupled with the fluorescence detection was developed for a specific estimation of ledipasvir. The separation was achieved on plates of silica gel 60 F254 using ethylacetate: hexane: acetonitrile: triethylamine; (6: 3.5: 1.5: 0.5, $\mathrm{v}/\mathrm{v}/\mathrm{v}/\mathrm{v}$) as a mobile phase system. The method involved the exposure of the developed thin-layer chromatography plate of ledipasvir to strong ultraviolet irradiation, resulting in a great enhancement in the fluorescence properties of ledipasvir. The irradiated plates were scanned after the excitation at 315 $\mathrm{nm}$. The method provided a sufficient separation of ledipasvir from sofosbuvir with ${R}&#95;F$values of 0.28 and 0.36 for ledipasvir and sofosbuvir, respectively. The developed procedures were validated based on guidelines from the International Conference on Harmonization and Food and Drug Administration guidelines. The calibration curve was linear over the range of 5-50 $\mathrm{ng}/\mathrm{band}$. The excellent analytical features of the proposed method allow to the specific determination of ledipasvir in pharmaceutical tablets without interference from sofosbuvir or excipients. As the main elimination route for ledipasvir is via the fecal excretion (86%), the method was applied for the estimation of ledipasvir in fecal specimens with adequate recovery. In addition, the proposed method was applied for testing the content uniformity of ledipasvir in the pharmaceutical tablets., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In recent years, many studies have reported the frequent detection of antihypertensive agents such as sartans (olmesartan, valsartan, irbesartan and candesartan) in the influents and effluents of wastewater treatment plants (WWTPs) and in the superficial waters of rivers and lakes in both Europe and North America. In this paper, the degradation pathway for candesartan (CAN) was investigated by simulating the chlorination process that is normally used to reduce microbial contamination in a WWTP. Twelve isolated degradation byproducts (DPs), four of which were isolated for the first time, were separated on a C-18 column by employing a gradient HPLC method, and their structures were identified by combining nuclear magnetic resonance and mass spectrometry and comparing the results with commercial standards. On the basis of these results, a mechanism of formation starting from the parent drug is proposed. The ecotoxicity of CAN and its DPs was studied by conducting a battery of ecotoxicity tests; bioassays were performed using Aliivibrio fischeri (bacterium), Daphnia magna (planktonic crustacean) and Raphidocelis subcapitata (alga). The ecotoxicity results shed new light on the increased toxicity of DPs compared with the parent compound.

In this study, for the first time, we propose a sensitive colloidal gold-based lateral flow immunoassay (LFIA) that can be used to detect carbendazim residues in functional foods. The adoption of inline cleanup LFIA strips effectively improved background interference to reduce misjudgment of results. First, the hapten 2-(methylamino)-1H-benzo[d]imidazole-5-carboxylic acid was used to establish the carbendazim immunoassay method. Subsequently, colloidal gold-mAb preparation and LFIA detection conditions were systematically optimized. For root and fruit samples (ginseng, ginger, jujube, and Chinese wolfberry), the designed strips had a cutoff value of 8 ng/mL. For flower and seed samples (chrysanthemum, coix seed, and malt), the cutoff value was 12 ng/mL. Even in a complex matrix, the established LFIA method demonstrates satisfactory sensitivity and anti-interference ability. This method was successfully applied in detection of carbendazim residues in complex functional foods, and the assay results are consistent with those obtained via liquid chromatography-tandem mass spectrometry. In short, the proposed method is fast and sensitive and has strong anti-interference ability. Furthermore, it provides a new technical method highly relevant to the on-site rapid detection of carbendazim residues in complex sample matrix.

A ratiometric fluorescent sensor was facilely fabricated using innate fluorescence of carbendazim (MBC) and fluorescent UiO-67 to sensitively and selectively detect MBC in food matrixes. The innate fluorescence of MBC provided a signal at 311 nm (F 311 ), and the fluorescent UiO-67 at 408 nm (F 408 ) could recognize MBC through π-π stacking inducing fluorescent quenching relied on photoelectron transfer (PET). The ratio (F 311 /F 408 ) of the fluorescence enhancement of MBC and the quenching of UiO-67 linearly responded to the MBC concentrations of 0-47.6 μmol/L with a low limit of detection (LOD) of 3.0 × 10 -3 μmol/L. The reverse response signals of the sensor enhanced the sensitivity toward MBC and presented remarkable anti-interference capability in complex matrices. The as-prepared sensor was applied to detect MBC residues in apple, cucumber and cabbage, obtaining satisfactory accuracy and precision with the recovery of 90.82-103.45% and RSDs of lower than 3.03%., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Carbendazim is a systemic benzimidazole-type fungicide with broad-spectrum activity against fungi that undermine food products safety and quality. Despite its effectiveness, carbendazim constitutes a major environmental pollutant, being hazardous to both humans and animals. Therefore, fast and reliable determination of carbendazim levels in water, soil, and food samples is of high importance for both food industry and public health. Herein, an optical biosensor based on white light reflectance spectroscopy (WLRS) for fast and sensitive determination of carbendazim in fruit juices is presented. The transducer is a Si/SiO 2 chip functionalized with a benzimidazole conjugate, and determination is based on a competitive immunoassay format. Thus, for the assay, a mixture of an in-house developed rabbit polyclonal anti-carbendazim antibody with the standards or samples is pumped over the chip, followed by biotinylated secondary antibody and streptavidin. The WLRS platform allows for real-time monitoring of biomolecular interactions carried out onto the Si/SiO 2 chip by transforming the shift in the reflected interference spectrum caused by the immunoreaction to effective biomolecular adlayer thickness. The sensor is able to detect 20 ng/mL of carbendazim in fruit juices with high accuracy and precision (intra- and inter-assay CVs ≤ 6.9% and ≤9.4%, respectively) in less than 30 min, applying a simple sample treatment that alleviates any "matrix-effect" on the assay results and a 60 min preincubation step for improving assay sensitivity. Excellent analytical characteristics and short analysis time along with its small size render the proposed WLRS immunosensor ideal for future on-the-spot determination of carbendazim in food and environmental samples.

Benzimidazoles, commonly used as pesticides and veterinary drugs, have posed a threat to human health and the environment due to unreasonable use and lack of valid regulation. Therefore, an up-to-date and comprehensive summary of the pretreatment and analytical approaches in different substrates is urgently needed. The present review consequently updates and covers various newly developed pretreatment methods (e.g., cationic micellar precipitation, magnetic-solid phase extraction, hollow fiber liquid phase microextraction, disperse liquid-liquid microextraction-solidified floating organic drop, stir cake sorptive extraction, solid phase microextraction method, QuEChERS, and molecular imprinted polymer-based methods) since 2005. The review also elaborates and discusses different determination methods (e.g., newly developed HPLC and related methods, improved spectrofluorimetry methods, capillary electrophoresis, and the electrochemical sensor). Furthermore, some critical points and prospects are highlighted, to describe the trends in this area., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The concurrent use of oral encorafenib (Braftovi, ENF) and binimetinib (Mektovi, BNB) is a combination anticancer therapy approved by the United States Food and Drug Administration (USFDA) for patients with BRAFV600E/V600K mutations suffering from metastatic or unresectable melanoma. Metabolism is considered one of the main pathways of drug elimination from the body (responsible for elimination of about 75% of known drugs), it is important to understand and study drug metabolic stability. Metabolically unstable compounds are not good as they required repetitive dosages during therapy, while very stable drugs may result in increasing the risk of adverse drug reactions. Metabolic stability of compounds could be examined using in vitro or in silico experiments. First, in silico metabolic vulnerability for ENF and BNB was investigated using the StarDrop WhichP450 module to confirm the lability of the drugs under study to liver metabolism. Second, we established an LC-MS/MS method for the simultaneous quantification of ENF and BNB applied to metabolic stability assessment. Third, in silico toxicity assessment of ENF and BNB was performed using the StarDrop DEREK module. Chromatographic separation of ENF, BNB, and avitinib (an internal standard) was achieved using an isocratic mobile phase on a Hypersil BDS C 18 column. The linear range for ENF and BNB in the human liver microsome (HLM) matrix was 5-500 ng/mL ( R 2 ≥ 0.999). The metabolic stabilities were calculated using intrinsic clearance and in vitro half-life. Furthermore, ENF and BNB did not significantly influence each other's metabolic stability or metabolic disposition when used concurrently. These results indicate that ENF and BNB will slowly bioaccumulate after multiple doses.

Aim: Bioanalytical methods undergo many revisions and modifications throughout drug development to meet the objectives of the study and development program. Results: Validated LC-MS/MS methodology used to quantify abemaciclib and four metabolites in human plasma is described. The method, initially validated to support the first-in-human study, was successfully modified to include additional metabolites as in vitro and in vivo information about the activity and abundance of human metabolites became available. Consistent performance of the method over time was demonstrated by an incurred sample reanalysis passing rate exceeding 95%, across clinical studies. An overview of the numerous methods involved during the development of abemaciclib, including the quantification of drugs evaluated as combination regimens and used as substrates during drug-drug interaction studies, is presented. Conclusion: Robust bioanalytical methods need to be designed with the flexibility required to support the evolving study objectives associated with registration and post-registration trials.

Molecular spectroscopy has been widely used to identify pesticides. The main limitation of this approach is the difficulty of identifying pesticides with similar molecular structures. When these pesticide residues are in trace and mixed states in plants, it poses great challenges for practical identification. This study proposed a state-of-the-art method for the rapid identification of trace (10 mg·L -1 ) and multiple similar benzimidazole pesticide residues on the surface of Toona sinensis leaves, mainly including benzoyl (BNL), carbendazim (BCM), thiabendazole (TBZ), and their mixtures. The new method combines high-throughput terahertz (THz) imaging technology with a deep learning framework. To further improve the model reliability beyond the THz fingerprint peaks (BNL: 0.70, 1.07, 2.20 THz; BCM: 1.16, 1.35, 2.32 THz; TBZ: 0.92, 1.24, 1.66, 1.95, 2.58 THz), we extracted the absorption spectra in frequencies of 0.2-2.2 THz from images as the input to the deep convolution neural network (DCNN). Compared with fuzzy Sammon clustering and four back-propagation neural network (BPNN) models (TrainCGB, TrainCGF, TrainCGP, and TrainRP), DCNN achieved the highest prediction accuracies of 100%, 94.51%, 96.26%, 94.64%, 98.81%, 94.90%, 96.17%, and 96.99% for the control check group, BNL, BCM, TBZ, BNL + BCM, BNL + TBZ, BCM + TBZ, and BNL + BCM + TBZ, respectively. Taking advantage of THz imaging and DCNN, the image visualization of pesticide distribution and residue types on leaves was realized simultaneously. The results demonstrated that THz imaging and deep learning can be potentially adopted for rapid-sensing detection of trace multi-residues on leaf surfaces, which is of great significance for agriculture and food safety.

Due to the excessive use of fungicides, pesticide residues have become a growing concern in recent years. Herein, we demonstrated an easy-prepared and low-cost surface enhanced Raman Scattering (SERS) chip composed of 3D silver microspheres (AgMSs) pattern for the quantitative testing of carbendazim in Chinese tea. Compared with the common monolayer SERS substrate, the 3D patterns formed by self-assembly AgMSs with fine nanostructure can offer much more aggregation-induced hotspots and generate strong 3D synergetic effects. Furthermore, when the thickness of the 3D pattern exceeded 6 μm, we replaced the conductive supporting coatings using the glass slides to reduce the cost without any impact on SERS properties. The prepared 3D chips achieved the determination of carbendazim within the linear range of 0.1-10 mg/L and the detection limit of 0.01 mg/L. It is simple and sensitive enough for the detection of most pesticide residues or other harmful organic molecules in our food or environment., (Copyright © 2020. Published by Elsevier Ltd.)