Alien species water hyacinth realizes waste into treasure: The preparation of biomass sorbent to determine benzoylurea insecticides in tea products.

A fast and effective analytical method with biomass solid-phase microextraction sorbent combined with a high-performance liquid chromatography-ultraviolet detector was proposed for the determination of benzoylurea (BU) insecticides in tea products. The novel sorbent was prepared by activating and then carbonizing water hyacinth with a fast growth rate and low application value as raw material and showed a high specific surface area and multiple interactions with analytes, such as electrostatic action, hydrogen bonding, and π-π conjugation. After optimizing the three most important extraction parameters (pH [X1], sample loading rate [X2], and solution volume [X3]) by Box-Behnken design, the as-established analytical method showed good extraction performance: excellent recovery (80.13%-106.66%) and wide linear range (1-400 µg/L) with a determination coefficient of 0.9992-0.9999, a low limit of detection of 0.02-0.1 µg/L and the satisfactory practical application results in tea products. All these indicate that the water hyacinth-derived material has the potential as a solid-phase extraction sorbent for the detection and removal of BU insecticides from tea products, and at the same time, it can also achieve the effect of rational use of biological resources, maintaining ecological balance, turning waste into treasure, and achieving industrial production.

A developed and validated centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method for rapid quantification of unbound lenvatinib in human plasma.

In clinical practice, the determination of unbound drug concentration is very important for dose adjustment and toxicity prediction because only the unbound fraction can achieve a pharmacological effect. A fast, sensitive and accurate analytical method of centrifugal ultrafiltration coupled with high performance liquid chromatography-tandem mass spectrometry method was developed and applied to allow the quantification of unbound lenvatinib concentration. The application of linear regression analysis was used to examine the effects of centrifugal force, centrifugal time, and protein content on ultrafiltrate volume (Vu). The results indicated that the centrifugal force and centrifugal time have an influence on Vu that is significantly positive (P < 0.05). This developed method with good linearity (r2 = 0.9996), good accuracy (bias % ≤ 2.24 %), good precision (CV % ≤ 7.10 %), and good recovery (95.46 %-106.46 %) was suitable for routine clinical practice and studies. Particularly, the ultrafiltration membrane had no non-specific binding to lenvatinib. The unbound fractions can be separated in just 15 min. This method was applied to quantify clinical samples and to determine the plasma protein binding and unbound fraction of lenvatinib. This study provides a more effective and promising method for determination of unbound lenvatinib. It could be beneficial to measure the unbound concentration of lenvatinib in personalized medicine and therapeutic drug monitoring in routine clinical practice.

In situ formation of solidified supramolecular solvent based dispersive liquid-liquid microextraction for the enrichment of phenylurea herbicides in water, fruit juice, and milk.

A convenient, efficient, and green dispersive liquid-liquid microextraction based on the in situ formation of solidified supramolecular solvents combined with high performance liquid chromatography was developed for the determination of four phenylurea herbicides in liquid samples, including monuron, monolinuron, isoproturon, and chlortoluron. Herein, a novel supramolecular solvent was prepared by the in situ reaction of [P4448]Br and NH4PF6, which had the advantages of low melting point, high density, and good dispersibility. In addition, the microscopic morphology and physical properties of supramolecular solvent were characterized, and the extraction conditions were optimized. The results showed that the analytes had good linearity (R2 > 0.9998) within the linear range. The limits of detection and quantification for the four phenylurea herbicides were in the range of 0.13-0.19 µg L-1 and 0.45-0.65 µg L-1, respectively. The prepared supramolecular solvent is suitable for the efficient extraction of phenylurea herbicides in water, fruit juice, and milk.

Identification of a Phase I mechanism gene of rice (OsCYP1) in response to isoproturon.

The long-term use of isoproturon may threaten food security and human health. Cytochrome P450 (CYP or P450) can catalyze the biosynthetic metabolism, and play a crucial role in the modification of plant secondary metabolites. Therefore, it is of great importance to explore the genetic resources for isoproturon degradation. This research focused on a phase I metabolism gene (OsCYP1) with significant differential expression in rice under isoproturon pressure. Specifically, the high-throughput sequencing results of rice seedling transcriptome in response to isoproturon stress were analyzed. The molecular information and tobacco subcellular localization of OsCYP1 were studied. The subcellular localization of OsCYP1 in tobacco was assessed, where it is located in the endoplasmic reticulum. To analyze the expression of OsCYP1 in rice, the wild-type rice was treated with 0-1 mg/L isoproturon for 2 and 6 days, and qRT-PCR assays were conducted to detect the transcription levels. Compared with the control group, the expression of OsCYP1 in shoots was progressively upregulated after exposure to isoproturon, with 6.2-12.7-fold and 2.8-7.9-fold increases in transcription levels, respectively. Moreover, treatment with isoproturon upregulated the expression of OsCYP1 in roots, but the upregulation of transcripts was not significant except for 0.5 and 1 mg/L isoproturon at day 2. To confirm the role of OsCYP1 in enhancing isoproturon degradation, the vectors overexpressing OsCYP1 were transformed into recombinant yeast cells. After exposure to isoproturon, the growth of OsCYP1-transformed cells was better than the control cells, especially at higher stress levels. Furthermore, the dissipation rates of isoproturon were increased by 2.1-, 2.1- and 1.9-fold at 24, 48 and 72 h, respectively. These results further verified that OsCYP1 could enhance the degradation and detoxification of isoproturon. Collectively, our findings imply that OsCYP1 plays vital role in isoproturon degradation. This study provides a fundamental basis for the detoxification and regulatory mechanisms of OsCYP1 in crops via enhancing the degradation and/or metabolism of herbicide residues.

Aryl ketones-derived porous organic polymer for enrichment and sensitive detection of phenylurea herbicides in water, tea drink and mushroom samples.

Three aryl ketones-derived porous organic polymers (ATP-POPM, ATP-POPP and ATP-POPO) were fabricated through the aldol condensation reaction of acetylated triphenylsilane precursor (ATP) with different aromatic aldehydes for the first time. The ATP-POPM exhibited superior extraction capacity toward phenylurea herbicides (PUHs). A sensitive method for the simultaneous determination of six PUHs in water, tea drink and mushroom samples was developed with ATP-POPM as solid phase extraction adsorbent prior to high performance liquid chromatography ultraviolet detection. Under the optimized conditions, the linear response of PUHs was 0.09-80.0 ng mL-1 for water, 0.18-100.0 ng mL-1 for tea drinks and 4.50-200.0 ng g -1 for mushroom samples. The detection limits (S/N=3) of the method were 0.03-0.10 ng mL-1, 0.06-0.18 ng mL-1, 1.50-4.50 ng g -1 for water, tea drink and mushroom, respectively. The method recoveries for spiked samples were in the range of 80.7%-116.0%, with relative standard deviations less than 10.3%. The results proved that the established method was sensitive and suitable to detect PUHs with acceptable accuracy and precision. This work provided a powerful tool to synthesize promising adsorbent by aldol condensation reaction for detecting six PUHs simultaneously in real samples.

Monoclonal Antibody-Based Immunosensor for the Electrochemical Detection of Chlortoluron Herbicide in Groundwaters.

Chlortoluron (3-(3-chloro-p-tolyl)-1,1-dimethyl urea) is an herbicide widely used in substitution to isoproturon to control grass weed in wheat and barley crops. Chlortoluron has been detected in groundwaters for more than 20 years; and dramatic increases in concentrations are observed after intense rain outbreaks. In this context; we developed an immunosensor for the determination of chlortoluron based on competitive binding of specific monoclonal antibodies on chlortoluron and immobilized biotinylated chlortoluron; followed by electrochemical detection on screen-printed carbon electrodes. The optimized immunosensor exhibited a logarithmic response in the range 0.01-10 µg·L-1; with a calculated detection limit (LOD) of 22.4 ng·L-1; which is below the maximum levels allowed by the legislation (0.1 µg·L-1). The immunosensor was used for the determination of chlortoluron in natural groundwaters, showing the absence of matrix effects.

Electrochemistry-coupled to liquid chromatography-mass spectrometry-density functional theory as a new tool to mimic the environmental degradation of selected phenylurea herbicides.

In vitro and in vivo experimental models, mainly based on cell cultures, animals, healthy humans and clinical trials, are useful approaches for identifying the main metabolic pathways. However, time, cost, and matrix complexity often hinder the success of these methods. In this study, we propose an alternative non-enzymatic method, using electrochemistry (EC) coupled to liquid chromatography (LC) - high resolution mass spectrometry (HRMS) - DFT theoretical calculations (EC/LC-MS/DFT) for the mimicry/simulation of the environmental degradation of phenylurea herbicides, and for the mechanism elucidation of this class of herbicides. Fenuron, monuron, isoproturon, linuron, monolinuron, metoxuron and chlortoluron were selected as relevant model compounds. The intended compounds are oxidized by EC, separated by LC and detected using electrospray ionization HRMS. The main oxidation products were hydroxylated compounds obtained by substitution and addition reactions. Unstable quinone imines/methines, rarely observed by conventional methods, have been identified during the oxidative degradation of phenylurea herbicides for the first time in this study. Some were directly observed and the others were trapped by glutathione GSH. Reactions such as hydrolytic substitutions (-Cl/+OH and -C3H7/+OH and -CH3/+OH and -OCH3/+OH), aromatic hydroxylation, alkyl carbon hydroxylation, dehydrochlorination/dehydromethylation/dehydromethoxylation and conjugation have been successfully mimicked. The obtained results, supported by theoretical calculations, are useful for simulating/understanding and predicting the oxidative degradation pathways of pesticides in the environment.

Fabrication of a Magnetic Fluorinated Covalent Organic Framework for the Selective Capture of Benzoylurea Insecticide Residue in Beverages.

Efficient capture of benzoylurea insecticide (BU) residue in food is a vital procedure for food safe monitoring. Herein, a core-shell structured magnetic fluorinated covalent organic framework with good magnetic responsiveness and abundant fluorine affinity sites was successfully synthesized, suitable for magnetic solid-phase extraction (MSPE) of BUs. Using a room-temperature synthesis strategy, the magnetic fluorinated covalent organic framework was fabricated by in situ polymerization of 1,3,5-tris(4-aminophenyl) triazine (TAPT) and 2,3,5,6-tetrafluoroterephthaldehyde (TFTA) on the surface of carboxylated Fe3O4 nanoparticles. The competitive adsorption experiment and molecular simulation verified that this magnetic fluorinated covalent organic framework possesses favorable adsorption affinity for BUs. This magnetic fluorinated covalent organic framework could be easily regenerated and reused at least eight times with no reduction of enrichment performance. Combining this magnetic fluorinated covalent organic framework-based MSPE with high-performance liquid chromatography-tandem mass spectrometry, a novel sensitive method for the analysis of BUs was developed. In yellow wine and fruit juice samples, good linear correlations were obtained for BUs in the range of 10-2000 and 20-4000 ng·L-1, respectively. The limit of quantitation of the BUs ranged from 1.4 to 13.3 ng·L-1 in the two beverage matrices. Desirable precision was achieved, with intraday and interday relative standard deviations lower than 11%.

LC-MS/MS method for the quantification of the anti-cancer agent infigratinib: Application for estimation of metabolic stability in human liver microsomes.

Infigratinib (INF) is a novel small molecule, administered orally, which acts as a human fibroblast growth factor receptors (FGFRs) inhibitor. FGFRs are a family of receptor tyrosine kinases (RTK) reported to be upregulated in various tumor cell types. In 1 December 2020, BridgeBio Pharma Inc. announced FDA approval of INF as a New Drug Application, granting it Priority Review for the treatment of cholangiocarcinoma (CCA). Thus, the current study aimed to establish a validated LC-MS/MS method to estimate the INF concentration in the HLM matrix. In silico prediction of INF metabolism was done using the StarDrop® WhichP450™ module to verify its metabolic stability. An accurate and efficient LC-MS/MS analytical method was developed for INF metabolic stability evaluation. INF and duvelisib (DVB) (internal standard; IS) were eluted using an isocratic mobile phase with a C18 column as a stationary reversed phase. The established LC-MS/MS method showed a linear range over 5-500 ng/mL (r2 ≥ 0.9998) in human liver microsomes (HLMs). The sensitivity of the method was confirmed at its limit of quantification (4.71 ng/mL), and reproducibility was indicated by inter- and intra-day accuracy and precision (within 7.3%). The evaluation of INF metabolic stability was assessed, which reflected an intrinsic clearance of 23.6 µL/min/mg and in vitro half-life of 29.4 min. The developed approach in the current study is the first LC-MS/MS method for INF metabolic stability assessment. Application of the developed method in HLM in vitro studies suggests that INF has a moderate extraction ratio, indicating relatively good predicted oral bioavailability.

A core-shell structured magnetic covalent organic framework as a magnetic solid-phase extraction adsorbent for phenylurea herbicides.

In this work, a core-shell structured magnetic covalent organic framework named as M-TpDAB was constructed with 3,3'-diaminobenzidine (DAB) and 1,3,5-triformylphloroglucinol (Tp) as building units. M-TpDAB was characterized by infrared spectroscopy, nitrogen adsorption-desorption isotherms, powder X-ray diffraction, scanning electron microscopy and transmission electron microscopy. Using the M-TpDAB as adsorbent, a simple and highly effective method was proposed for preconcentrating phenylurea herbicides before high performance liquid-phase chromatography analysis. In the optimized conditions, a good linearity was achieved within the range of 0.15-100 ng mL-1 for water sample, 1.0-100.0 ng mL-1 for tea drink samples. The limits of detection for the analytes were 0.05-0.15 ng mL-1 for water sample and 0.30-0.50 ng mL-1 for drink samples. Satisfactory recoveries of spiked target compounds were in the range of 84.6%-105% for water sample and 80.3%-102% for tea drink samples. Finally, the M-TpDAB based method was successfully used to determine phenylurea herbicides in tea drinks and water samples, demonstrating a good alternative for analyzing trace level of phenylurea herbicides in water samples.

In-syringe temperature-controlled liquid-liquid microextraction based on solidified floating ionic liquid for the simultaneous determination of triazine and phenylurea pesticide in vegetable protein drinks.

A novel in-syringe temperature-controlled liquid-liquid microextraction based on solidified floating ionic liquid (in-syringe TC-LLME-SFIL) combined with high performance liquid chromatography was developed for the simultaneous determination of monuron, chlorotoluron, atrazine, monolinuron, propazine and prometryn in commercial vegetable protein drinks. The samples were deproteinized by trichloroacetic acid and further cleaned up by solid phase extraction column. The ionic liquid tributyldodecylphosphonium tetrafluoroborate ([P4 4 4 12]BF4) was used as extraction solvent and dispersed into the depurated sample solution to form fine droplets with the assistance of heating and vortex. With the help of an ice bath, the ionic liquid phase solidified and floated on the surface of aqueous phase. After separation from the aqueous phase, the solidified ionic liquids were dissolved with acetonitrile and the resulting solution was analyzed by high performance liquid chromatography. Some extraction parameters, including type and amount of adsorbent, type and amount of ionic liquids, amount of NaCl, melting temperature and time of ionic liquid, vortex time, pH of sample solution, ice bath temperature and time, were investigated and optimized by single-factor experiment, Plackett-Burman design and Box-Behnken design. The results showed that good linearities (r ≥ 0.9994) were obtained in the concentration range of 7.8-1000.0 µg/L. The limits of detection and quantification were in the range of 0.25-2.59 µg/L and 0.82-8.63 µg/L, respectively. The spiked recoveries were 81.26-118.42% with the relative standard deviation (RSD, n = 3) lower than 8.17%. The present method was successfully applied to the simultaneous determination of triazine and phenylurea herbicides in vegetable protein drinks.

Rapid analysis of forchlorfenuron in fruits using molecular complex-based dispersive liquid-liquid microextraction.

The main sample preparation method for analysis of pesticide residues in fruits is QuEChERS. In this study, a novel sample preparation method using molecular complex-based dispersive liquid-liquid microextraction is introduced with detection of forchlorfenuron by high-performance liquid chromatography coupled with diode array and mass spectrometric detection. Sample treatment involves initial extraction of a 5 g sample with 3 mL acetonitrile, and then the selective concentration of the analyte is performed using 150 µL tributyl phosphate by forming intermolecular hydrogen bonds with the analyte. The extraction mechanism was proved using ATR-FTIR. Under the optimised conditions, recovery rates varied between 88% and 107% for various sample matrices spiked at three levels in the range 0.01-0.1 mg kg-1. Intra-day and inter-day repeatabilities were in the ranges of 2.2-8.0% and 1.6-9.5%, respectively. Detection limit and quantitation limit were 0.33 µg kg-1 and 1.09 µg kg-1 for diode-array detection; 0.01 µg kg-1 and 0.04 µg kg-1 for tandem mass spectrometry detection. This method was successfully applied for the analysis of 149 various fruits. The analyte was found in 4 of the 149 samples and the contents were not over the specific maximum residue limit established by domestic and international regulations.

Fabrication of carboxyl functionalized microporous organic network coated stir bar for efficient extraction and analysis of phenylurea herbicides in food and water samples.

Fabrication of novel coatings continues to be an area of great interest and significance in the development and application of stir bar sorptive extraction (SBSE). In this work, a carboxyl-enriched microporous organic network (MON-2COOH) coated stir bar was designed and fabricated as a novel adsorbent for efficient extraction of four phenylurea herbicides (PUHs) before their determination by high-performance liquid chromatography coupled with photodiode array detector (HPLC-PDA). The MON-2COOH was represented as an effective adsorbent for PUHs due to its large surface area, rigid porous structure, aromatic pore walls and the desired hydrogen bonding sites of introduced carboxyl groups. Variables affecting the SBSE of target analytes were optimized in detail. Under the optimal extraction conditions, favorable correlation coefficients (R2 > 0.996) in the linear range 0.10-250 µg L-1, low limits of detection (LODs, S/N = 3) of 0.025-0.070 µg L-1 and good enrichment factors (46-49) were obtained. Besides, the proposed SBSE-HPLC-PDA method was successfully applied to determine trace PUHs in food and environmental water samples with recoveries in the range of 80.0-104.8% and the precisions (relative standard deviations, RSDs) lower than 9.9% (n = 3). This work revealed the potential of MONs in SBSE of trace contaminants from environmental samples.

Phosphonium-based deep eutectic solvent coupled with vortex-assisted liquid-liquid microextraction for the determination of benzoylurea insecticides in olive oil.

In this study, a novel method using a phosphonium-based deep eutectic solvent coupled with vortex-assisted liquid-liquid microextraction was investigated for the enrichment and separation of five benzoylurea insecticides in olive oil. The experimental factors affecting the extraction efficiency, including the extractant type, deep eutectic solvent volume, extraction time, and extraction mode, were optimized. Under optimal conditions, good linearity was observed for all target analytes, with correlation coefficients (r) ranging from 0.9971 to 0.9998; the limits of detection were in the range of 1.5 to 7.5 µg/L, and the recoveries of analytes using the proposed method ranged between 66.9 and 111.0%. The simple, rapid, and effective method was successfully applied for detecting target analytes in olive oil sample.

Room-temperature synthesis of magnetic covalent organic frameworks for analyzing trace benzoylurea insecticide residue in tea beverages.

A novel magnetic covalent organic framework (NH2-Fe3O4@COF) was prepared using a simple room-temperature synthesis in this study. These magnetic particles exhibited high adsorption performance with short adsorption time (10 min) for six benzoylurea insecticides (BUs) as magnetic solid-phase extraction (MSPE) adsorbents. Quantum chemistry calculation demonstrated that adsorption mechanism was primarily attributed to strong halogen bonds between electronegative O atoms of COF and electropositive F atoms of BUs as well as potential hydrophobic effect. Wide linearities (10-1000 ng·L-1) and low limits of detection (0.06-1.65 ng·L-1) for six analytes were obtained via liquid chromatography-tandem mass spectrometry. Applicability of the proposed method was further evaluated by analyzing four kinds of original tea beverages. Recoveries of six BUs in spiked samples ranged from 80.1% to 108.4%.

Dissipation kinetics and consumer risk assessment of novaluron + lambda-cyhalothrin co-formulation in cabbage.

Cabbage, one of the most popular vegetables in the world is infested by several insect-pests and diseases. Novaluron, a chitin synthesis inhibitor and lambda-cyhalothrin, a synthetic pyrethroid group insecticide are used to manage insect-pests on cabbage. The dissipation kinetics and risk assessment of combination formulation (novaluron 9.45% + lambda-cyhalothrin 1.9%) with different modes of action has not yet been investigated in cabbage. Multi-location supervised field trials were therefore, conducted in different agro-climatic regions of India for safety evaluation of the combination product. The co-formulation at the recommended (novaluron 750 g a.i. ha-1 + lambda-cyhalothrin 750 g a.i. ha-1) and double the recommended (novaluron 1500 g a.i. ha-1 + lambda-cyhalothrin 1500 g a.i. ha-1) dose was sprayed on the cabbage crop. The samples were extracted and cleaned up using a modified QuEChERS method, and the residues analyzed by GC-ECD and GC-MS. The half-life (t1/2) varied between 1.77 and 2.51 and 2.00-3.38 days for novaluron and 1.36-2.24 and 1.69-3.82 days for lambda-cyhalothrin in cabbage at respective doses. The Food Safety and Standards Authority of India (FSSAI) has set the MRL of 0.7 mg kg-1 for novaluron at PHI of 5 days, and no MRL is set for lambda-cyhalothrin in cabbage. On the basis of OECD MRL calculator, the MRLs of 0.6 and 1.5 mg kg-1 for novaluron and lambda-cyhalothrin, respectively were calculated at the respective doses at PHI of 3 days. Hazard quotient (HQ) <1, theoretical maximum daily intake (TMDI) < acceptable daily intake (ADI) and < maximum permissible intake (MPI), percent acute hazard index (% aHI) <1, and percent chronic hazard index (% cHI) <1 for both novaluron and lambda-cyhalothrin suggested that the combination formulation is safe and will not pose any dietary risk to the consumers. The study will be helpful to conduct risk assessment of other pesticides/combination pesticides on food crops on which their MRLs have not yet been fixed.

Facile construction of magnetic azobenzene-based framework materials for enrichment and sensitive determination of phenylurea herbicides.

Exploring new material as adsorbent for the efficient enrichment of pollutants is always of great significance in analytical chemistry. In this work, a magnetic azobenzene framework (labeled as MAzo) was constructed as a magnetic solid phase extraction (MSPE) adsorbent by a simple and environmentally benign strategy. The MAzo exhibited the attractive features of strong magnetism, outstanding adsorption performance, as well as good reusability. Combining MAzo-based MSPE with high performance liquid-phase chromatography, a simple and effective method was developed for simultaneous determination of four phenylurea herbicides in pear juice and apple juice samples. Under optimized experimental conditions, the method offered low limits of detection of 0.05-0.15 ng mL-1, high recoveries of 86.7-109.2% with RSD less than 7%. Density functional theory calculation indicated that the good adsorption performance of MAzo for PUHs can be ascribed to the strong H-bonding forces and weak π-π interactions. The facile, green, low-cost synthesis method together with the excellent adsorption performance endows the MAzo great application prospect in sample preparation.

Sensitive simultaneous voltammetric determination of the herbicides diuron and isoproturon at a platinum/chitosan bio-based sensing platform.

Phenylurea herbicides are persistent contaminants, which leads their transport to the surface and ground waters, affecting human and aquatic organisms. Different analytical methods have been reported for the detection of phenylureas; however, several of them are expensive, time-consuming, and require complex pretreatment steps. Here, we show a simple method for the simultaneous electrochemical determination of two phenylurea herbicides by differential pulse adsorptive stripping voltammetry (DPAdSV) using a modified platinum/chitosan electrode. The one-step synthesized platinum/chitosan PtNPs/CS was successfully characterized by TEM, XRPD, and FT-IR, and applied through the sensing platform designated as PtNPs/CS/GCE. This bio-based modified electrode is proposed for the first time for the individual and/or simultaneous electrochemical detection of the phenylurea herbicides diuron and isoproturon compounds extensively used worldwide that present a very similar chemical structure. Electrochemical and interfacial characteristics of the modified electrode were evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). It was found that the oxidation mechanism of diuron and isoproturon occurs in two different pathways, with a peak-to-peak definition of ca. 0.15 V. Under differential pulse adsorptive stripping voltammetry (DPAdSV) optimized conditions, the limit of detection (LOD) was estimated as 7 µg L-1 for isoproturon and 20 µg L-1 for diuron (Ed = +0.8 V; td = 100 s). The proposed method was successfully applied to the determination of both analytes in river water samples, at three different levels, with a recovery range of 90-110%. The employment of the bio-based sensing platform PtNPs/CS/GCE allows a novel and easy analytical method to the multi-component phenylurea herbicides detection.

A LC-MS/MS method for therapeutic drug monitoring of sorafenib, regorafenib and their active metabolites in patients with hepatocellular carcinoma.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of sorafenib (SORA), its N-oxide active metabolite and of regorafenib (REGO) and its two active metabolites regorafenib N-oxide and N-desmethyl regorafenib N-oxide in hepatocellular carcinoma patients' plasma. A proper analytes' separation was obtained with Synergi Fusion RP column (4 µm, 80 Å, 50 × 2.0 mm) using a gradient elution of 10 mM ammonium acetate with 0.1% formic acid (mobile phase A) and methanol:isopropanol (90:10, v/v, mobile phase B) containing 0.1% formic acid. The analysis was then performed by electrospray ionization in negative mode coupled with a triple quadrupole mass spectrometry, API 4000QT, monitoring two transitions for each analyte, one for the quantification and the other for confirmation. The method could be easily applied to the clinical practice thanks to the short run (7 min), the low amount of patient plasma necessary for the analysis (5 µL) and the fast sample processing based on protein precipitation. The method was therefore fully validated according to FDA and EMA guidelines. The linearity was assessed (R2≥0.998) over the concentration ranges of 50-8000 ng/mL for SORA and REGO, and 30-4000 ng/mL for their metabolites, that appropriately cover the therapeutic plasma concentrations. The presented method also showed adequate results in terms of intra- and inter-day accuracy and precision (CV ≤ 7.2% and accuracy between 89.4% and 108.8%), recovery (≥85.5%), sensitivity, analytes stability under various conditions and the absence of the matrix effect. Once the validation was successfully completed, the method was applied to perform the Cmin quantification of SORA, REGO and their metabolites in 54 plasma samples collected from patients enrolled in a clinical study ongoing at the National Cancer Institute of Aviano.

Extraction of benzoylurea pesticides from tea and fruit juices using deep eutectic solvents.

In this study, low-density deep eutectic solvent combined with dispersive liquid-liquid microextraction was applied to the extraction of five benzoylurea insecticides (BUs, including diflubenzuron, triflumuron, hexaflumuron, flufenoxuron, and chlorfluazuron) from beverages. Then the extracted and concentrated samples were analyzed and detected using the high-performance liquid chromatography combined with an ultraviolet detector. The DESs were synthesized by [P14,6,6,6]Cl as hydrogen bond acceptor and tetradecyl alcohol as hydrogen bond donor, and then characterized by Fourier transform infrared spectroscopy. In the experiment, the key factors affecting the extraction efficiency were screened by Plackett-Burman design and optimized with the central composite design. The extraction recovery rates were 85.91-95.12%. The limits of detection and correlation coefficients of the method were 0.30-0.60 µg L-1 and 0.9992-0.9997. Finally, the method was applied to determine the BUs in four beverage samples, and satisfactory recoveries, within the range of 76.87-101.19% were achieved. The present method has the potential to be applied to the detection of BUs in aqueous samples.