γ-ray radiolysis of dihydroxyurea in nitric acid and its radiolytic products

Journal of Radioanalytical and Nuclear Chemistry - Dihydroxyurea (DHU) is a new salt-free reducing agent applied for the separation of Pu and Np from U in spent fuel reprocessing. This paper...     

Rapid screening and quantification of sulfonate derivatives in white peony root by UHPLC–MS–MS

A rapid ultra-high-performance liquid chromatographic–tandem mass spectrometric (UHPLC–MS–MS) method has been developed for rapid screening and quantitative analysis of sulfonate derivatives (SDs) in commercial white peony root. Separation was performed on an Agilent Zorbax Eclipse Plus-C18 column by gradient elution with acetonitrile–0.1% (v/v) formic acid as the mobile phase. In-source fragmentation was used to generate the characteristic fragment ion at m/z 259 and to screen for nine SDs. Detection of these SDs was further performed in multiple reaction monitoring (MRM) mode to improve sensitivity and to quantify the two SDs paeoniflorin sulfonate and benzoylpaeoniflorin sulfonate. The method was validated for specificity, linearity, limits of detection and quantification, precision, accuracy, and matrix effects. Nine commercial white peony root samples were examined by use of this method, which revealed great variety in the paeoniflorin sulfonate and benzoylpaeoniflorin sulfonate content.     

A UHPLC–MS/MS method for the simultaneous determination of vancomycin,norvancomycin, meropenem,and moxalactam in human plasma and its clinical application

We developed an ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method to determine four antibacterial drugs in human plasma for clinical usage. Samples were prepared using protein precipitation with methanol. Chromatographic separation was accomplished in 4.5 min on a BEH C18 column (2.1 × 50 mm, 1.7 μm) using a gradient elution of methanol and water (containing 7.71 g/L concentrated ammonium acetate, adjusted to pH 6.5 with acetic acid) at a flow rate of 0.4 mL/min. Positive electrospray was used for ionization. The method was linear in the concentration range 1–100 μg/mL for vancomycin, norvoncomycin, and meropenem; and 0.5–50 μg/mL for R-isomer of moxalactam and S-isomer of moxalactam. For all analytes, the intra- and inter-day accuracies and precisions were −8.47%–10.13% and less than 12%, respectively. The internal standard normalized recoveries and matrix effect were 62.72%–105.78% and 96.67%–114.20%, respectively. All analytes were stable at six storage conditions, with variations of less than 15.0%. The method was applied in three patients with central nervous system infection. The validated method might be useful for routine therapeutic drug monitoring and pharmacokinetic study.     

UHPLC–MS/MS method for the determination of bisphenol A and its chlorinated derivatives,bisphenol S,parabens, and benzophenones in human urine samples

In the present work, a new method based on a sample treatment by dispersive liquid–liquid microextraction (DLLME) for the extraction of six bisphenols (bisphenol A, bisphenol S, and monochloro-, dichloro-, trichloro-, and tetrachlorobisphenol A), four parabens (methyl-, ethyl-, propyl-, and butylparaben), and six benzophenones (benzophenone-1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8, and 4-hydroxybenzophenone) in human urine samples, followed by ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) analysis, is validated. An enzymatic treatment allows determining the total content of the target EDCs. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-¹³C₆, benzophenone-d₁₀, and bisphenol A-d₁₆ were used as surrogates. Limits of quantification ranging from 0.1 to 0.6 ng mL^?1 and interday variabilities (evaluated as relative standard deviations) from 2.0 to 13.8 % were obtained. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 94 to 106 %. A good linearity, for concentrations up to 300 ng mL^?1 for parabens and 40 ng mL^?1 for benzophenones and bisphenols, was also obtained. The method was satisfactorily applied for the determination of target compounds in human urine samples from 20 randomly selected individuals.     

Determination of lesinurad in rat plasma by a UHPLC–MS/MS assay

Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has been approved by the US Food and Drug Administration for combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with refractory gout. In the present study, a sensitive and specific ultra high-performance liquid chromatography with tandem mass spectrometry assay was established and verified for the determination of lesinurad in rat plasma and was described in details for the first time. Chromatographic separation of lesinurad and diazepam (internal standard, IS) was performed on a Rapid Resolution HT C18 column (3.0 × 100 mm, 1.8 µm) using methanol–water (70:30, v/v) as the mobile phase at a flow rate of 0.3 mL/min. Lesinurad and IS were extracted from plasma by liquid–liquid extraction using ethyl acetate. The mass spectrometric detection was carried out using an electrospray ionization source in positive mode. Multiple reaction monitoring was used for quantification of the precursor to product ion at m/z 405.6 → 220.9 for lesinurad and m/z 285.1 → 192.8 for IS. The assay was well validated for selectivity, accuracy, precision, recovery, linearity, matrix effects, and stability. The verified method was applied to obtain the pharmacokinetic parameters and concentration–time profiles for lesinurad after oral/intravenous administration in rats. The study might provide an important reference and a necessary complement for the qualitative and quantitative evaluation of lesinurad.     

Preparation of the Ca–diclofenac complex in solid state

Two ONNO type naphtaldehyde derivative Schiff base compounds were reduced and two symmetric phenol-amine ligands containing naphthalene groups were obtained; bis-N,N′[(2-hydroxy-1-naphtyl) methyl]-1,3-propanediamine (NAFL^H) and bis-N,N′[(2-hydroxy-1-naphtyl) methyl]-2,2′-dimetyhyl-1,3-propanediamine (NAFLDM^H). Homotrinuclear Ni(II) complexes of these ligands were prepared. The solid-state molecular structures of representative nickel complex of NAFLDM^H were determined using single crystal X-ray diffraction analysis. The terminal Ni(II) ions were found to be situated in between the donor atoms of the organic ligand. The central Ni(II) ion was observed to be bonded via two different μ-bridges. The phenolic oxygens and carboxylate ion were seen to form two different μ-bridges. TG analysis proved that the compounds have different thermal characteristics than those cited in literature. The complexes showed extreme exothermic degradation reactions in inert atmosphere. The complexes are ruptured with a two stepped exothermic reaction which appears huge heat over 300 °C. The heat appeared in O₂ atmosphere is observed to be higher than the heat appeared in inert atmosphere. Revealed heat is observed to be higher than the conventional explosive materials.     

Simultaneous Determination of 42 Pesticides and Herbicides in Chicken Eggs by UHPLC–MS/MS and GC–MS Using a QuEChERS-Based Procedure

A quick, easy, cheap, rugged, effective, and safe (QuEChERS)-based method has been validated for the extraction of 42 pesticides and herbicides including organophosphorus pesticides (OPPs), carbamate pesticides (CBs), herbicides (HBs), organochlorine pesticides (OCPs), and synthetic pyrethroid pesticides (PYRs) from chicken eggs. The QuEChERS-based extraction procedure was followed by cleanup steps using C18 and primary secondary amine sorbents. The supernatant was analyzed by ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) and gas chromatography–mass spectrometry (GC–MS). The OPPs, CBs, and HBs were quantified by UHPLC–MS/MS, while the OCPs and PYRs were detected by GC–MS. The limits of quantification ranged from 0.01 to 8.5 μg kg⁻¹, and the analyte recoveries were in the range of 64.9–123.2 %. Furthermore, the repeatabilities (intra-day and inter-day) were good, and linear matrix-matched calibration curves were obtained. Acetochlor was identified in concentrations ranging from 0.27 to 0.44 μg kg⁻¹ in four samples from 80 chicken eggs. The method was successfully demonstrated for the fast and reliable analysis of pesticides and herbicides in chicken egg samples.

     

Development of an analytical method for the determination of the residues of four pyrethroids in meat by GC–ECD and confirmation by GC–MS

The development of an analytical method for the determination of four selected pyrethroid insecticides at residue level in beef meat is presented. Acetone and petroleum ether at 40-60 degrees C were chosen as extraction solvents. A two-step clean-up was performed using an Extrelut NT3-C(18) system followed by a Florisil column, with disposable, ready-to-use cartridges. Instrumental analysis was carried out on a gas chromatograph equipped with an electron capture detector (GC-ECD), using matrix-matched and internal standard calibration techniques. Confirmatory analysis by GC-MS was performed. Recoveries at the EU Maximum Residue Limit (MRL), 0.5 x MRL and 1.5 x MRL levels and the repeatabilities were widely satisfactory. The main advantage of the method was the reduction of analysis time as compared with previously published works. The applicability of the method to different matrices and pesticide classes will be investigated.     

Establishment of fingerprint of Gegen Qinlian decoction and its formula compatibility groups using UHPLC–MS/MS and its study to spectrum–effect relationship

Based on the establishment of analytical method of ultra-high performance liquid chromatography-tandem mass spectrometry fingerprint and obtaining pharmacodynamic information of the effects on IL-4, IL-10, TNF-α, and IFN-γ of serum and interstitial fluid of the damp-type ulcerative colitis mice of Gegen Qinlian decoction and its formula compatibility groups, the spectrum–effect relationship study was performed by using the method of principal component analysis. The study built the common pattern of UHPLC–MS/MS fingerprint of Gegen Qinlian decoction and formula compatibility groups and identified eight components which were rooted in monarch and subject drugs and represented the whole pharmacodynamic information of Gegen Qinlian decoction. The research on formula compatibility and spectrum–effect relationship can provide scientific basis for revealing pharmacodynamic material basis and compatibility regularity of Gegen Qinlian decoction.     

Systematization of the results of the chromatography–mass spectrometry identification of the products of quercetin oxidation by atmospheric oxygen in aqueous solutions

The coordination of the results of different works for the systematization of the structures of products previously detected in the complex samples is an important stage in the interpretation of the results of the identification of the components of complex samples of natural origin by chromatography–mass spectrometry with the low reproducibility of their mass spectra under the conditions of electrospray ionization and limited reference information. The data processing of this kind was carried out for the products of the oxidation of the most common natural flavonoid quercetin (3,5,7,3',4'-pentahydroxyflavone) by atmospheric oxygen in weakly alkaline aqueous alcohol solutions. For the correlation of peaks in chromatograms with the structures of oxidation products, their reversed-phase HPLC retention indices in the scale of reference n-alkyl phenyl ketones were determined for the first time. It was confirmed that not all of the oxidation products are stable in solution; some of them can accumulate or disappear during the storage of the samples.     

Development of a green stability-indicating HPLC–DAD method for the determination of donepezil hydrochloride in the presence of its related substance and degradation products

A simple, eco-friendly, stability-indicating HPLC method was developed for the determination of donepezil hydrochloride (DH) in tablet dosage form in the presence of its pharmacopoeia-related compound (donepezil-related compound A) and its different degradation products. The chromatographic conditions were optimized to achieve the highest performance parameters using Zorbax Eclipse Plus C18 rapid resolution column (4.6?×?100?mm, 3.5?µm), with a mobile phase composed of 72.5% acetate buffer pH 5.5 and 27.5% ethanol, flowing at 1?mL?min^?1. The diode array detector (DAD) was set at 315?nm and the column oven was adjusted at 45°C. Linear response (r?=?0.9999) was observed over the range of 2–28?µg?mL^?1 of donepezil, with detection and quantitation limits of 0.031 and 0.103?µg?mL^?1, respectively. Forced degradation studies were performed on standard DH and test Demepezil® 5-mg tablets under various conditions and the method was found to be stability indicating. The purity of DH peak was confirmed using the DAD. In the developed method, two principles of green chromatography were adopted (reduce and replace) by reducing solvent consumption through the utilization of a short column (10?cm) with a smaller particle size (3.5?µm) instead of a normal 25?cm with a 5?µm particle size and by replacing hazardous solvents of the official United States Pharmacopoeia method as acetonitrile with ethanol. Furthermore, the greenness of the method was assessed using three assessment tools.     

Online solid phase extraction LC–MS/MS method for the analysis of succinate dehydrogenase inhibitor fungicides and its applicability to surface water samples

A sensitive and selective analytical method, based on online solid phase extraction coupled to LC–MS/MS, was developed and validated to determine traces of several recently introduced fungicides in surface water and wastewater. The list of target analytes included eight succinate dehydrogenase inhibitors (bixafen, boscalid, fluopyram, flutolanil, fluxapyroxad, isopyrazam, penflufen, and penthiopyrad), and two other fungicides with different modes of action, fenpyrazamine and fluopicolide. Detection and quantification limits in various matrices were in the range of 0.1 to 2 and 0.5 to 10 ng/L, respectively. Moderate signal suppression was observed in surface water (≤15 %) and wastewater (≤25 %) and was well compensated by the selected internal standard. The intra- and inter-day precisions were generally <10 and <20 %, respectively. The applicability of the method was demonstrated in a study on the occurrence of fungicides in the river Glatt, Switzerland, that drains a catchment area of 419 km² with a substantial proportion of agricultural land. Of the studied compounds, only boscalid and fluopicolide were detected in flow-proportional weekly composite samples, generally at low concentrations up to 15 and 5 ng/L, respectively. While fluopicolide was detected in only 30 % of the samples above the LOD of 0.5 ng/L, boscalid was detected in all samples analyzed between March and October 2012. Graphical Abstract

Concentration of the fungicides boscalid and fluopicolide in flow-proportional weekly-composite watersamples from River Glatt, Switzerland in 2012     

Determination of antifouling pesticides and their degradation products in marine sediments by means of ultrasonic extraction and HPLC–APCI–MS

A method has been developed for the simultaneous determination of antifouling pesticides and some of their degradation products, e.g. dichlofluanid, diuron, demethyldiuron, 1-(3,4-dichlorophenyl)urea, sea-nine, Irgarol 1051 and one of its metabolites (2-methylthio-4-tert-butylamino-s-triazine) in marine sediments. The determination of these compounds in sediment samples was performed by means of methanolic ultrasonic extraction then clean-up on an Isolute ENV+ solid phase extraction (SPE) cartridge. The resulting extract was then analyzed by reversed-phase high-performance liquid chromatography coupled with atmospheric-pressure chemical-ionization mass spectrometry in negative and positive ion modes (HPLC–APCI–MS). Recovery ranged from 54–109% for the antifouling agents and their degradation products. The determination limits for the different compounds varied between 0.2 and 1.6 μg kg^–1 dry sediment. The analytical procedure was successfully applied to the determination of these pesticides and their degradation products in marine sediment samples from different marinas of the Catalan coast. The compounds detected were: diuron, dichlofluanid, demethyldiuron, sea-nine, and Irgarol 1051. The highest concentrations were those of diuron and Irgarol 1051 – 136 and 88 μg kg^–1, respectively.     

Nontargeted UHPLC–MS for the Study of the Diversity of Flavonoid Glycosides in Different Fermented Teas

Chromatographia - Although black tea and dark tea are both fermented teas, their fermentation processes are varied a lot and strongly affect their chemical components. The flavonoids which are the...     

Validation and application of sub-2 μm core–shell UHPLC–UV–ESI–Orbitrap MS for identification and quantification of β-carotene and selected cleavage products with preceding solid-phase extraction

A validated ultrahigh-performance liquid chromatography method using 1.7 μm core–shell particles is presented for the identification and quantification of β-carotene (BC) and related cleavage products (CPs) in primary cell culture media. Besides BC, apo-4′-, apo-8′-, apo-10′-, and apo-12′-carotenals, as well as 5,6-epoxy-β-carotene, were selected as target analytes. Detection was performed via an 80-Hz diode array detector and an electrospray ionization–linear quadrupole ion trap–Orbitrap XL mass spectrometer, both hyphenated in series. Total analysis time was below 6 min with peak widths <12 s. Addition of trifluoroacetic acid and tetrahydrofuran to the mobile phase allowed for the mass spectrometric detection of BC and related CPs and reduced peak tailing due to improved solubility of hydrophobic analytes. Intra-day and inter-day precision for UV and mass spectrometric detection were ≤1.5 % for retention times and ≤5.1 % for peak areas. Instrumental linearity was confirmed by Mandel’s fitting test between 0.25 (or 1.00 μg/mL) and 5.00 μg/mL for UV detection. The higher sensitivity of mass spectrometric detection allowed for the coverage of three concentration domains between 0.025 and 5.00 μg/mL in linearity testing. Homoscedasticity was confirmed between 0.10 and 5.00 μg/mL for Orbitrap XL MS. The limits of quantification were between 52.6 and 889.4 ng/mL for UV detection and between 19.3 and 102.4 ng/L for mass spectrometric detection. Offline solid-phase extraction from culture media fortified with BC and CPs provided intra- and inter-day recoveries between 65.8 and 102.4 % with coefficients of variation ≤6.2 %. Primary rat hepatocyte cultures treated with BC and subjected to different oxidative stress conditions contained 5,6-epoxy-BC and apo-4′-carotenal besides residual BC. Apparently, 5,6-epoxy-BC was formed in the medium via autoxidation of BC by ambient oxygen.     

Phase equilibria in the solid state and colour properties of the CuO–In2O3 system

Phase equilibria up to solidus line in CuO?CIn₂O₃ system have been investigated using XRD and DTA/TG methods. According to the results, only one compound of the formula Cu₂In₂O₅ formed in the system studied. Its thermal stability was determined in the air and argon proving that the compound did not melt but underwent decomposition. The decomposition of Cu₂In₂O₅ in the air atmosphere began at 1080?°C, while in argon at 835?°C. Additional studies were undertaken to determine the hitherto unknown colour properties of samples representing the CuO?CIn₂O₃ system in the equilibrium state.     

Inclusion of Paracetamol into β-cyclodextrin nanocavities in solution and in the solid state

We report on steady-state UV-visible absorption and emission characteristics of Paracetamol, drug used as antipyretic agent, in water and within cyclodextrins (CDs): β-CD, 2-hydroxypropyl-β-CD (HP-β-CD) and 2,6-dimethyl-β-CD (Me-β-CD). The results reveal that Paracetamol forms a 1:1 inclusion complex with CD. Upon encapsulation, the emission intensity enhances, indicating a confinement effect of the nanocages on the photophysical behavior of the drug. Due to its methyl groups, the Me-β-CD shows the largest effect for the drug. The observed binding constant showing the following trend: Me-β-CD>HP-β-CD>β-CD. The less complexing effectiveness of HP-β-CD is due to the steric effect of the hydroxypropyl-substituents, which can hamper the inclusion of the guest molecules. The solid state inclusion complex was prepared by co-precipitation method and its characterization was investigated by Fourier transform infrared spectroscopy, 1H NMR and X-ray diffractometry. These approaches indicated that Paracetamol was able to form an inclusion complex with CDs, and the inclusion compounds exhibited different spectroscopic features and properties from Paracetamol.     

High-Throughput Screening of Drugs of Abuse in Urine by Supported Liquid–Liquid Extraction and UHPLC Coupled to Tandem MS

A qualitative method, involving supported liquid–liquid extraction (SLE) and ultra high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS–MS), was developed for the rapid tentative identification of various drugs of abuse in urine. In this study, 28 drugs and metabolites were covered by the screening procedure. Before analysis, urine samples were extracted by SLE and good extraction recoveries were obtained for most investigated compounds. The UHPLC strategy was then selected for the rapid separation of amphetamines, cocaine, opiates and related compounds in urine. Using columns packed with sub-2 µm particles, analysis time was reduced down to 2 min, while maintaining acceptable performance. Finally, the detection was by tandem MS operating in the single reaction monitoring (SRM) mode. The most intense transition was selected for the different drugs and SRM dwell times set at 5 ms, to maintain sufficient data points across the narrow UHPLC peaks. The tentative identification of the drugs of interest, including amphetamines, opiates and cocaine, was based on both, retention times and mass spectrometry information. With the proposed method, limits of detection were estimated at about 1 ng mL^?1 and the applicability was assessed by successfully analyzing several samples of drug abusers. Finally, this study demonstrates the potential of UHPLC coupled to tandem MS for the rapid screening of drugs of abuse in urine.