Synthesis of heterocycles by domino-Knoevenagel–hetero-Diels–Alder reactions

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Determination of adrenolytic drugs by SPME–LC–MS

Five adrenolytic drugs have been analyzed by liquid chromatography–mass spectrometry (LC–MS). Samples were prepared by solid-phase microextraction (SPME) using polypyrrole fibers coated on stainless steel support as an adsorbent for the drugs. Adsorption efficiencies were 95% and were close for all the drugs investigated. Relative standard deviations (RSD), calculated for samples prepared in standard solutions, were in the range 2.5–13%, however RSD values for the drugs in human plasma were 2.5–4.5%. Using LC–MS the limit of detection (LOD) and the limit of quantification (LOQ) were in the ranges 0.11–0.18 and 0.39–0.54 ng mL⁻¹, respectively, for the five drugs.     

Sensitive redox speciation of neptunium by CE–ICP–MS

Capillary electrophoresis (CE) was used to separate the neptunium oxidation states Np(IV) and Np(V), which are the only oxidation states of Np that are stable under environmental conditions. The CE setup was coupled to an inductively coupled plasma mass spectrometer (Agilent 7500ce) using a Mira Mist CE nebulizer and a Scott-type spray chamber. The combination of the separation capacity of CE with the detection sensitivity of inductively coupled plasma mass spectrometry (ICP-MS) allows identification and quantification of Np(IV) and Np(V) at the trace levels expected in the far field of a nuclear waste repository. Limits of detection of 1?×?10^-9 and 5?×?10^-10 mol L^-1 for Np(IV) and Np(V), respectively, were achieved, with a linear range from 10^-9 to 10^-6 mol L^-1. The method was applied to study the redox speciation of the Np remaining in solution after interaction of 5?×?10^-7 mol L^-1 Np(V) with Opalinus Clay. Under mildly oxidizing conditions, a Np sorption of 31% was found, with all the Np remaining in solution being Np(V). A second sorption experiment performed in the presence of Fe²⁺ led to complete sorption of the Np onto the clay. After desorption with HClO₄, a mixture of Np(IV) and Np(V) was found in solution by CE–ICP–MS, indicating that some of the sorbed Np had been reduced to Np(IV) by Fe²⁺.     

Trace analysis of high-purity graphite by LA–ICP–MS

Laser-ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) has been established as a very efficient and sensitive technique for the direct analysis of solids. In this work the capability of LA–ICP–MS was investigated for determination of trace elements in high-purity graphite. Synthetic laboratory standards with a graphite matrix were prepared for the purpose of quantifying the analytical results. Doped trace elements, concentration 0.5 μg g^–1, in a laboratory standard were determined with an accuracy of 1% to ± 7% and a relative standard deviation (RSD) of 2–13%. Solution-based calibration was also used for quantitative analysis of high-purity graphite. It was found that such calibration led to analytical results for trace-element determination in graphite with accuracy similar to that obtained by use of synthetic laboratory standards for quantification of analytical results. Results from quantitative determination of trace impurities in a real reactor-graphite sample, using both quantification approaches, were in good agreement. Detection limits for all elements of interest were determined in the low ng g^–1 concentration range. Improvement of detection limits by a factor of 10 was achieved for analyses of high-purity graphite with LA–ICP–MS under wet plasma conditions, because the lower background signal and increased element sensitivity. Received: 4 January 2001 / Revised: 27 March 2001 / Accepted: 28 March 2001     

Determination of diquat by flow injection–chemiluminescence

A simple, economic, sensitive and rapid method for the determination of the pesticide diquat was described. This new method was based on the coupling of flow injection analysis methodology and direct chemiluminescent detection; to the authors’ knowledge, this approach had not been used up to now with this pesticide. It was based on its oxidation with ferricyanide in alkaline medium; significant improvements in the analytical signal were achieved by using high temperatures and quinine as sensitiser. Its high throughput (144 h⁻¹), together with its low limit of detection (2 ng mL⁻¹), achieved without need of preconcentration steps, permitted the reliable quantification of diquat over the linear range of (0.01–0.6) μg mL⁻¹ in samples from different origins (river, tap, mineral and ground waters), even in the presence of a 40-fold concentration of paraquat, a pesticide commonly present in the commercial formulations of diquat. Figure Quartz luminometer cell     

Phytochemical characterization of bioactive compounds composition of Rosmarinus eriocalyx by RP–HPLC–ESI–QTOF–MS

Rosmarinus eriocalyx (rosemary or Elyazir) is an endemic species growing in arid steppe and rocky mountain in the South-West Algeria. This plant is well known in Algeria and Morocco due to its medicinal properties. However, little is known about its phytochemical composition. For this purpose, natural antioxidant compounds from R. eriocalyx were recovered by solid-liquid extraction and characterized by reversed-phase high-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry using negative and positive ionization modes. This analytical methodology enabled the characterization of 101 compounds, which were distributed in five major categories namely hydroxycinnamic acid derivatives, hydroxybenzoic acid derivatives, flavonoids, phenolic diterpenes and phenolic triterpenes. Moreover, the studied extract generally showed free radical-scavenging and reductive abilities in the range of butylated hydroxyanisole, butylated hydroxytoluene, α-tocopherol^, and ascorbic acid. Therefore, the result suggests that the aqueous-methanolic extract of R. eriocalyx could serve as a potential source of antioxidants.     

Analysis of Nanafrocin in Foodstuffs of Animal Origin by LC–MS–MS

A new, rapid, and efficient method, multiple reaction monitoring liquid chromatography–tandem mass spectrometry, has been developed for analysis of nanafrocin in foodstuffs of animal origin. The researchers used a C₁₈ stationary phase coupled with triple-quadrupole tandem mass spectrometry in negative-electrospray mode. The limits of detection (LOD) and quantification (LOQ) were 0.005 and 0.01 mg kg^?1, respectively, in the matrixes. Detector response was found to be a linear function of concentration over the range 0.005–0.1 mg kg^?1 in each matrix. Mean overall recovery (n = 10) of nanafrocin varied from 71 to 101%. The results show that identification and quantification of nanafrocin residues in foodstuffs of animal origin can be successfully achieved by use of the proposed LC–MS–MS method.     

Preparation of nanoparticles of oxides by the citrate–nitrate process

This paper reports preparation of nanoparticles of oxides by the citrate–nitrate process and the effect of metal ions on the thermal decomposition characteristics of the corresponding citrate–nitrate gel precursors. In order to understand the effect of metal ions on the thermal decomposition characteristics of the precursors, we have prepared a series of single component oxides such as MO, where M = Zn, MO₂, where M = Sn, Ce, Zr, and M₂O₃ where M = Al, Fe, Bi. In all the cases the citrate to nitrate ratio was fixed at 0.3. In order to ascertain the decomposition characteristics of the gel samples, TG/DTA studies were performed on the dried gel samples. After complete physico-chemical characterization of the precursors and the calcined products, it could be concluded that the nature of decomposition of the precursors depends largely on the nature of the metal ions. Finally, the advantages of the citrate–nitrate process such as its high degree of reproducibility, its potential for large-scale production of nano-crystalline ceramic oxide powders and its lower cost could be established based on a series of experiments and examples.     

A study of the extraction of plutonium from planchets by Aridus–ICP–SFMS

Two extraction processes of plutonium (Pu) on planchets from alpha spectrometry (AS) have been evaluated by inductively coupled plasma sector field mass spectrometry with a desolvator system (Aridus–ICP–SFMS). The samples were traced with known concentrations of ²³⁹Pu (1.2 × 10³ fg) and ²⁴²Pu (2 × 10³ fg) followed by an electrodeposition in planchets, according to the Hallstadius method. The processes of extraction were carried out with 50 mL of 0.36 mol L^?1 HNO₃ every 30 min up to 180 min in a glass beaker at 60 °C. The first process was on a hotplate and the second used an ultrasonic system. Finally, samples were evaporated to dryness, and resuspended in 10 mL of 0.72 mol L^?1 HNO₃ for evaluation. The results showed that at 120 min, a ~70 % recovery of ²³⁹Pu and a ~80 % recovery of ²⁴²Pu in both processes were obtained. The average recoveries of ²³⁹Pu and ²⁴²Pu at 180 min using the hotplate in plate were 93.4 ± 4.6 and 93.7 ± 4.2 % respectively, and with the ultrasonic system were 96.0 ± 4.3 and 98.2 ± 1.0 % respectively. In conclusion, both processes are suitable for Pu extraction, and Aridus–ICP–SFMS is an essential technique for the reassessments and quantification of Pu. In addition, procedural blanks spiked with 1 × 10² fg mL^?1 U were prepared for each process, in order to study the contribution of the ²³⁸U on the background signal at m/z = 239, which was 0.5 ± 0.2 cps, indicating that the contribution of ²³⁸U on the ²³⁹Pu signal was negligible. Furthermore, this methodology can be applied to sample planchets with environmental, food, biological and nuclear origin, and thereby to avoid repetitive analysis when Pu concentration determined by AS are under minimum detectable activities.     

Characterisation of Ni carbonate-bearing minerals by UV–Vis–NIR spectroscopy

Four nickel carbonate-bearing minerals from Australia have been investigated to study the effect of Ni for Mg substitution. The spectra of nullaginite, zaratite, widgiemoolthalite and takovite show three main features in the range of 26,720–25,855 cm⁻¹ (ν₁-band), 15,230–14,740 cm⁻¹ (ν₂-band) and 9,200–9,145 cm⁻¹ (ν₃-band) which are characteristic of divalent nickel in six-fold coordination. The Crystal Field Stabilization Energy (CFSE) of Ni²⁺ in the four carbonates is calculated from the observed ³A_2g(³F) → ³T_2g(³F) transition. CFSE is dependent on mineralogy, crystallinity and chemical composition (Al/Mg-content). The splitting of the ν₁- and ν₃-bands and non-Gaussian shape of ν₃-band in the minerals are the effects of Ni-site distortion from regular octahedral. The effect of structural cation substitutions (Mg²⁺, Ni²⁺, Fe²⁺ and trivalent cations, Al³⁺, Fe³⁺) in the carbonate minerals is noticed on band shifts. Thus, electronic bands in the UV–Vis–NIR spectra and the overtones and combination bands of OH and carbonate ion in NIR show shifts to higher wavenumbers, particularly for widgiemoolthalite and takovite.     

Quantification of phytochelatins in plants by reversed-phase HPLC–ESI–MS–MS

An on-line HPLC–ESI–MS–MS method has been developed for determination of glutathione and phytochelatins (PC) in plant tissues. For sample pretreatment, dithiothreitol (DTT) must be added at the very beginning, as an anti-oxidant. Optimization of instrumental conditions i.e. composition of HPLC mobile phase, ionization efficiency of the electrospray interface, and MS–MS detection in the multiple ion-monitoring mode, are the central aspects of this work. A polystyrene-packed column was found to be superior to a standard silica-packed reversed-phase column. A concave quadratic gradient of ammonium formate buffer and acetonitrile was found to be optimum. The limits of quantitation were 0.2 mol kg^–1 plant tissue for glutathione and PC. The method has been applied to analysis of tissue samples from Vicia faba grown in Cd-containing nutrient solutions.Dedicated to the memory of Wilhelm Fresenius     

Thermal decomposition of RDX/AP by TG–DSC–MS–FTIR

The method of TG–DSC–MS–FTIR simultaneous analysis has been used to study the thermal decomposition mechanism of the RDX/AP (1/2) mixture. TG–DSC showed that there were two mass loss processes for thermal decomposition of RDX/AP. The first one was mainly ascribed to the thermal decomposition of RDX. Addition of AP to RDX causes decomposition to take place abruptly, after melting, resulting in a very sharp and strong peak at lower temperature. The apparent activation energies, calculated by model-free Friedman method, of this process were negative. The second mass loss process of RDX/AP was confirmed to be the thermal decomposition of AP, catalyzed by RDX. This process can be divided into three stages, which were an nth-order autocatalytic and two one-dimensional diffusion stages, respectively. There was a competition among the formation reactions of N₂O, HNCO, and HCl for the first stage and between NO₂ and N₂O for the later two stages. The production of N₂O dominated in the second stage, while NO₂ did in the third stage.     

Determination of Pitavastatin in Human Plasma by LC–MS–MS

A simple and rapid LC–MS–MS assay was developed and validated for the quantitative determination of pitavastatin in human plasma. Sample pretreatment involved simple protein precipitation by addition of acetonitrile. Separation was on an Agilent 1.8 μm Zorbax SB-C18 column (150 mm × 4.6 mm) at 25 °C using isocratic elution with methanol–0.1% formic acid in water (85:15, v/v) at a flow rate of 0.4 mL min^?1. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the ion transitions m/z 422.0 → 290.1 for pitavastatin, and m/z 330.1 → 192.1 for paroxetine (IS). LC–MS–MS was found to improve the quantitation of pitavastatin in plasma and was successfully applied in pharmacokinetic studies.     

Determination of the MRI contrast agent Gd-DTPA by SEC–ICP–MS

The simultaneous determination of Gd³⁺ and Gd-DTPA (DTPA: diethylenetriamino-pentaacetic acid), often used as contrast agent, is described. The proposed approach combines size-exclusion chromatography (SEC) and inductively coupled plasma–mass spectrometry (ICP–MS) for element-selective detection in order to determine also high-molecular Gd-complexes if present. This method was applied to the analysis of urine samples of a patient to whom Gd-DTPA was intravenously administered. The results showed that no conversion or adsorption of Gd-DTPA could be observed in any sample, even free Gd³⁺ could not be detected. Urine excretion behaviour was monitored and it was proved that Gd-DTPA was almost completely (>99%) excreted by urination within one day. Traces of Gd-DTPA could be measured in hair samples, but extraction with tetramethylammonium hydroxide (TMAH) resulted in degradation of Gd-DTPA.     

Modification of tricine–SDS–PAGE for online and offline analysis of phosphoproteins by ICP-MS

This study describes a modification to tricine sodium dodecyl sulphate polyacrylamide gel electrophoresis to make it more effective for the separation of low molecular mass proteins and for coupling with inductively coupled plasma mass spectrometry (ICP-MS). The modified method employs low-percentage polyacrylamide gels (7–10%) (w/v) and low reagent concentrations that provide efficient separations, good quantitation and low matrix levels that are compatible with ICP-MS. Using phosphopeptides as a model system, and offline analysis, we obtained recoveries of 73% (w/v) in a 9% gel compared with 55% in a conventional 16% gel. Online coupling was achieved by modification of a standard commercially available gel electroelution apparatus and casting of the gel into a 7.3-cm-long tube. Online separation of a digest of β-casein was demonstrated with recovery of the mono- and tetraphosphopeptides, which were identified by comparison with peptide standards. A mass balance study with the standards yielded recoveries of 95% for tetraphosphopeptides and 48% for monophosphopeptides. The factors affecting the separations and recoveries are discussed in detail. The detection limits for 10-μL samples of the mono- and tetraphosphopeptides were 0.7 μM (7 pmol) and 0.2 μM (2 pmol) respectively.     

Synthesis of complex Si–O–N–H derivatives by molecular bombardment of silicon and silicon dioxide

Bombardment of a silicon target in a high vacuum with a molecular beam (mixture of high energy H₂+N₂, obtained by charge exchange) and a thermal beam of O₂ produces on the target a variety of compounds. The target is then bombarded by the same molecular beams which produce, extracted by an electrostatic field at an energy of about 10 keV, molecular ions due to the compounds thus formed. These ions are analysed (electromagnet) to give a primary spectrum of ions according to their mass, which are individually selected and dissociated in a collision cell (same H₂+N₂ mixture). Mass analysis of the dissociation fragments leads to the identification of silicon clusters (Si)_n and of Si–O–N–H derivatives, the fragmentations of which permit a definitive determination of their molecular complexity. Dissociation spectra have thus been obtained for some of the most intense peaks of the primary spectrum, on the one hand, and on the other hand for some peaks of lower intensity but of special interest to us (see below). The composition of the fragments is confirmed by the study of the satellite ions derived from the natural 28, 29 and 30 isotopes of silicon, and by the use of deuterium instead of hydrogen. None of the Si–O–N–H derivatives obtained was apparently known earlier. It is shown that some of these molecules (those ‘of special interest to us’) may be identical with sila-analogues of standard amino acids and of nucleic bases: the fact that their fragmentations are identical with those of the corresponding carbon analogues speaks in favour of a structural identity. However, one cannot yet distinguish between the various possible isomeric arrangements, as none of them has been independently prepared, which excludes a direct comparison with reference samples, and as these isomers might give identical fragments; we hope to be able to resolve this ambiguity later. Anyhow, the substances formed are the most complex molecular silicon derivatives so far produced: e.g. Si₂O₂NH₅, Si₃O₂NH₇, Si₄O₃NH₉, Si₄O₂N₂H₄, Si₄ON₃H₅, Si₅O₃N₂H₁₀, Si₅O₂NH₁₁, corresponding to sila-glycine, sila-alanine, sila-threonine, sila-uracile, sila-cytosine, sila-valine, sila-glutamine, – or isomers. Similar results have been obtained using a silicon dioxide target and high energy molecular beams of hydrogen and of nitrogen, without thermal oxygen, or with a carborundum target. © 2000 Académie des sciences / Éditions scientifiques et médicales Elsevier SASmolecular impact / silicon derivatives / amino-acid silicon analogues     

Examination of the oxidation resistance of Cr–Mo–V tool steel by thermal analysis

In the present study, the oxidation behavior of Cr–Mo–V tool steel was examined at different temperatures in air. The examination was conducted by means of thermogravimetric analysis, scanning electron microscopy, and X-ray diffraction (XRD). After non-isothermal oxidation from ambient temperature to 1000 °C, it was revealed that the specimen begins to oxidize over 700 °C, while over 800 °C the oxidation rate increases significantly. Finally over 900 °C, this rate has a considerable value, and the specimen's oxidation resistance is inadequate. From these results, four different oxidation temperatures (805, 835, 865, and 895 °C) were selected for the isothermal test, as referred above, which correspond to different oxidation rates, to determine the oxidation activation energy of the Cr–Mo–V specimens. Energy dispersive X-ray spectroscopy (EDX) and XRD phase identification of the as-formed scales showed that in every case, it contains two distinguishable regions. The inner layer is a mixture of chrome and iron oxides and the outer layer contains iron oxides and is also characterized by high porosity. This phenomenon was explained by the different diffusion coefficients of every element in the steel matrix.     

Simultaneous Analysis of Lipid-Soluble Constituents of Erxian Decoction by GC–MS

Erxian Decoction (EXD), a traditional Chinese medicine formula mainly composed of six Chinese herbs, was originally developed for menopausal syndromes and had been practiced since the 1950s in China. Previous studies only focused on the water-soluble compounds involved in EXD by LC or TLC. This study analyzed the whole profile of the volatile constituents contained in EXD to supplement its quality evaluation method. Several EXD samples were extracted with chloroform and ethyl acetate, respectively, to get the lipid-soluble chloroform and ethyl acetate fractions and compared their gas chromatographic profiles by GC–MS. The EXD samples were hydrolyzed with hydrochloric acid in a water-bath at 100 °C, neutralized with 40% NaOH, and finally extracted with ethyl acetate and chloroform for the quantification of the total sarsasapogenins contained in EXD. A total of 56 compounds belonging to a variety of natural product categories such as aromatic phenols, terpenes, fatty acids, ketones, esters, and aldehydes, etc. were identified from the chloroform and ethyl acetate extracts by using the online EI–MS characterization. The GC–MS method showed a linear response for sarsasapogenin quantification with r = 0.994. The intra-day and inter-day variations of precision and accuracy of the assay were less than 5%. This developed GC–MS method could thus be successfully applied for the identification of lipid-soluble constituents derived from EXD, and also for the accurate quantification of the total sarsasapogenins contained in the acid hydrolyzed EXD samples.