LC–QToF–MS method for quantification of ethambutol,isoniazid, pyrazinamide and rifampicin in human plasma and its application

In this research, we developed and validated a liquid chromatography coupled to mass spectrometry (LC–QToF–MS) method for simultaneous quantification of the anti-tuberculosis drugs ethambutol, isoniazid, pyrazinamide and rifampicin in human plasma. Plasma samples spiked with cimetidine (internal standard) were extracted using protein precipitation with acetonitrile containing 1% formic acid. Separation was performed using a C₁₈ column under flow gradient conditions with water and acetonitrile, both containing 5 mm ammonium formate and 0.1% formic acid. The method was validated according to the ANVISA and US Food and Drug Administration guidelines for bioanalytical method validation. The calibration curve was linear over a concentration range of 0.2–5 μg ml⁻¹ for ethambutol, 0.2–7.5 μg ml⁻¹ for isoniazid, 1–40 μg ml⁻¹ for pyrazinamide and 0.25–2 μg ml⁻¹ for rifampicin, all with adequate precision and accuracy. The method was reproducible, selective and free of carryover and matrix effects. The validated LC–QToF–MS method was successfully applied to real samples and shown to be applicable to future therapeutic and pharmacokinetic monitoring studies.     

Thermal properties of molten sulphur-oxyanionic salts

Lithium, sodium, potassium and ammonium bisulphate have been shown by detailed TG/DTA studies to have limited application as molten solvents. By contrast, the eutectic bisulphate systems, ammonium-potassium bisulphate and sodium-potassium bisulphate, appear to be excellent molten solvents in view of their low melting points, long liquid ranges and prolonged thermal stability at 200°. In contrast to previous studies, potassium pyrosulphate has been found to be an excellent molten solvent, provided rigorous preliminary drying procedures have been applied.

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Zusammenfassung An Hand eingehender TG/DTA-Untersuchungen wurde gezeigt, daß die Bisulfate von Lithium, Natrium, Kalium und Ammonium nur eine begrenzte Anwendung als geschmolzene Lösungsmittel finden können. Die eutektischen Bisulfat-Systeme Ammonium/ Kalium Bisulfat und Natrium/Kalium Bisulfat scheinen wegen ihrer niedrigen Schmelzpunkte, ihres weiten Flüssigkeitsbereichs und ihrer dauerhaften Thermostabilität bei 200° ausgezeichnete geschmolzene Lösungsmittel zu sein. Im Gegensatz zu früheren Untersuchungen erwies sich Kaliumpyrosulfat als ein ausgezeichnetes geschmolzenes Lösungsmittel, vorausgesetzt daß vorangehend strenge Trocknungsverfahren angewandt wurden.

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Résumé On montre par une étude TG/ATD approfondie que les hydrogénosulfates de lithium, de sodium, de potassium et d'ammonium n'ont qu'une application limitée en tant que solvants fondus. Les systèmes eutectiques des hydrogénosulfates ammonium/potassium et sodium/potassium paraissent, au contraire, être des solvants fondus excellents, en raison de leurs points de fusion bas, de leurs larges intervalles d'existence à l'état liquide et de leur stabilité thermique prolongée à 200°. Contrairement à des études antérieures, on a trouvé que le pyrosulfate de potassium est un solvant fondu excellent, à la condition d'appliquer un mode opératoire rigoureux lors du séchage préliminaire.

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The authors would like to thank Dr. C. Barraclough and Mr. M. Beyer of the Physical Chemistry Department, Melbourne University, for assistance with the Raman spectra.     

Use of carbon isotope analysis to understand semi-arid erosion dynamics and long-term semi-arid land degradation

Many semi-arid areas worldwide are becoming degraded, in the form of C(4) grasslands being replaced by C(3) shrublands, which causes an increase in surface runoff and erosion, and altered nutrient cycling, which may affect global biogeochemical cycling. The prevention or control of vegetation transitions is hindered by a lack of understanding of their temporal and spatial dynamics, particularly in terms of interactions between biotic and abiotic processes. This research investigates (1) the effects of soil erosion on the delta(13)C values of soil organic matter (SOM) throughout the soil profile and its implications for reconstructing vegetation change using carbon-isotope analysis and (2) the spatial properties of erosion over a grass-shrub transition to increase understanding of biotic-abiotic interactions by using delta(13)C signals of eroded material as a sediment tracer. Results demonstrate that the soils over grass-shrub transitions are not in steady state. A complex interplay of factors determines the input of SOM to the surface horizon of the soil and its subsequent retention and turnover through the soil profile. A positive correlation between event runoff and delta(13)C signatures of eroded sediment was found in all plots. This indicates that the delta(13)C signatures of eroded sediment may provide a means of distinguishing between changes in erosion dynamics over runoff events of different magnitudes and over different vegetation types. The development of this technique using delta(13)C signatures of eroded sediment provides a new means of furthering existing understanding of erosion dynamics over vegetation transitions. This is critical in terms of understanding biotic-abiotic feedbacks and the evolution of areas subject to vegetation change in semi-arid environments.     

On the existence of weak solutions of anisotropic generally restrained plates

This paper presents investigations of free vibration of anisotropic plates of different geometrical shapes and generally restrained boundaries. The existence and uniqueness of weak solutions of boundary value problems and eigenvalue problems which correspond to the statical and dynamical behaviour of the mentioned plates is demonstrated. It is determined that when the plates have corner points formed by the intersection of edges free or elastically restrained against translation, the corresponding bilinear forms maintain the V – ellipticity property.     

Thermal, spectral, and diffraction properties of Co-exchanged montmorillonite with 2-, 3-, and 4-hydroxyphenol

The influence of the 2-, 3-, and 4-OH phenols on the type of interaction with Co-exchanged montmorillonite and thermal properties of these materials were studied. The results of XRD, IR, and thermal (TG, DTG) analysis show that organic species are intercalated into the interlayer space of montmorillonite. Thermal decomposition in the temperature interval 20?C700?°C of studied samples with 2- and 3-hydroxyphenol proceeds in three steps (the release of adsorbed H₂O molecules, combustion/desorption of protonated hydroxy phenols and dehydroxylation), while the sample with 4-hydroxyphenol decompose in four steps (the new peak at ~222?°C corresponds to directly coordinated organic species). The effect of different position of the hydroxyl groups on the phenol ring on the thermal decomposition is evident.