Fully automated determination of eserine N-oxide in human plasma using on-line solid-phase extraction with liquid chromatography coupled with electrospray ionization tandem mass spectrometry

A sensitive and entirely automated solid-phase extraction/liquid chromatography/electrospray ionization tandem mass spectrometric (SPE/LC/ESI-MS/MS) method was developed and validated for the determination of eserine N-oxide (ENO), a cholinesterase inhibitor-like physostigmine in human plasma, for use in pharmacokinetic studies. ENO is light-sensitive and the use of a fully on-line process increased the reliability of the assay. Plasma samples previously mixed with neostigmine bromide to prevent in vitro degradation, and tacrine as internal standard (IS), were directly injected into the SPE/LC/ESI-MS/MS system. MS software piloted the overall system. MS/MS detection of ENO and the IS was performed in the positive ion ESI mode using multiple reaction monitoring. The linear calibration curve for ENO ranged from 25 pg ml(-1) to 12.5 ng ml(-1). The limit of quantitation was 25 pg ml(-1) with 250 microl of plasma injected. Precision, accuracy and stability tests were within the acceptable range and just one analyst is required to analyze 50 unknown samples a day five days per week, from the preparation of the samples (i.e. thawing and centrifugation) to data processing. A pilot pharmacokinetic study in three healthy volunteers treated with 4.5 mg of ENO (Génésérine3((R))) showed that the method was suitable for pharmacokinetic studies in humans.     

Direct determination of phosphorylated intracellular anabolites of stavudine (d4T) by liquid chromatography/tandem mass spectrometry

The original article to which this Erratum refers was published in Rapid Commun Mass Spectrom. 2001; 15 : 1401–1408.     

Real-space observation of spectral degeneracy breaking in a waveguide-coupled disk microresonator

We report on the real-space observation of resonant frequency splitting in a high-Q waveguide-coupled silicon-on-insulator microdisk resonator. Phase sensitive near-field analysis reveals the stationary nature of the two resonant states, and spectral investigations clearly show their orthogonality. These measurements emphasize the role of the coupling waveguide in this splitting phenomenon. The symmetry of the two stationary whispering gallery modes is clearly observed and is found to follow the axial symmetry of the waveguide-coupled microdisk as it has been reported by earlier theoretical predictions.     

Development and validation of a liquid chromatographic/tandem mass spectrometric assay for the quantitation of nucleoside HIV reverse transcriptase inhibitors in biological matrices

Besides liquid chromatographic (LC)/UV methods adapted to therapeutic drug monitoring, there is still a need for more powerful techniques that can be used for pharmacological research and clinical purposes. We developed an LC method coupled with tandem mass spectrometry (MS/MS) to separate, detect and quantify with high sensitivity the nucleoside analogues used in multitherapies (zidovudine, stavudine, zalcitabine, didanosine, lamivudine and abacavir) in plasma and in the intracellular medium. We worked on two essential issues: (i) the need to use two ionization modes in order to achieve the best sensitivity, which leads to the optimization of the chromatographic separation of drugs detected in the positive ionization mode and drugs detected in the negative ionization mode, and (ii) the need to optimize the extraction step in order to enhance sample recovery. The peripheral blood mononuclear cells were lysed in Tris buffer-MeOH. A clean-up procedure was performed by solid-phase extraction only for plasma samples. The LC separation was carried out on a Zorbax Stable Bond C(18) column followed by MS/MS analysis after electrospray ionization in either the negative or positive mode. The positive ionization mode was applied at the beginning of the run to detect zalcitabine and lamivudine, then the ionization mode was changed to negative for the detection of didanosine, stavudine, internal standard and zidovudine. The calibration range for all the analytes was 0.5-200 ng ml(-1). The recoveries were between 64 and 90%, with coefficients of variation (CVs) lower than 15%. The inaccuracy (bias) was +/-15% with CVs always lower than 12%. The analytes were stable at room temperature and in the extraction solvent for at least 24 h, after storage at -80 degrees C for 3 months, after three freeze-thaw cycles and in the injection solvent after 48 h at 4 degrees C. Together with the measurement of intracellular triphosphorylated metabolites thanks to the powerful plasma and intracellular assay method for intact drugs, it is possible to describe the behaviour of nucleoside analogues against HIV through plasma pharmacokinetics, cell membrane diffusion including drug transport involvement, and also the intracellular metabolism.     

Recent achievements and trends of research for geophysical prospection of archaeological sites

Our times are characterized by an increasing need for prospection particularly within the context of rescue archaeology. Geophysics has an important part to play due to its ability to identify some well defined targets as well as to investigate large areas. Several recent surveys, using carefully selected methods chosen in accordance with the type of expected remain or a combination of methods in order to refine or confirm the interpretation, have demonstrated the expertise of several organisations in a wide variety of archaeological contexts. However, important improvements are still to be expected from the laboratories. Our team, working within the framework of three dissertations, is investigating several original subjects, for which the initial results are presented and discussed here: (1) The use of magnetic susceptibility measurements on wide mesh grids in order to survey extensive areas immediately prior to their occupation or destruction by large modern equipment; (2) Experiments to test a new survey device (Slingram - CS150) able to measure the magnetic susceptibility of the ground; (3) Interpretation of a series of geophysical measurements integrated with other types of data into a G.I.S.     

Longitudinal and lateral low frequency head wave analysis in soft media

This article studies the influence of the head wave in the lateral and longitudinal components of the displacements generated by the radiation of low-frequency elastic waves in an isotropic and homogeneous soft solid. Low-frequency shear waves are used to characterize elastic properties of soft tissues. In this context, it is useful to have a detailed study of the low-frequency wave field in this kind of material. A soft medium is characterized by the fact that the head wave is found in the source's axis. Even though its amplitude is small compared with the shear wave, it is possible to be observed experimentally by recording consecutive ultrasonic A-lines while the low-frequency wave propagates inside the medium. A standard one-dimensional speckle tracking technique is employed to measure the displacements. Experimental results were interpreted through the exact Green's function solution to the half-space problem. According to the theoretical and experimental analysis, the head wave and surface related terms in general contribute to the displacements in the low-frequency range. This article thoroughly analyzes and experimentally shows the contribution of the head wave for the lateral component, which is not fully addressed by the literature.     

Diffraction effects in guided photonic band gap structure

The concept of the photonic band gap (PBG) structures stems from ideas of Yablonovitch. The idea is to design components so that they affect the properties of photons, in much the same way that ordinary semiconductor crystals affect the properties of electrons. In fact, the PBG structures forbid propagation of photons for a particular range of energy. They can be used to realise optical filters with large stop band and sharp transmission resonance. In the guided PBG structures, the existence of diffractive effects in the vertical dimension could limit the quality factor of such filters. In this paper, we have investigated the origin of diffraction losses in one-dimensional guided PGB structures using 2D and 3D numerical tools. We propose an analytical approach based on Bragg diffraction relation to explain these losses phenomenon. From this approach, the influence of some design parameters on the electromagnetic behaviour and the spectral response of PBG resonators will be explained.     

Luminescent Eu(III) and Gd(III) trisbipyridine cryptates: experimental and theoretical study of the substituent effects.

Synthesis, absorption spectra and luminescebce properties of a series of lanthanide trisbipyridine cryptates Ln within R-Bpy x R-Bpy x R-Bpy, where Ln = Eu, Gd and R = H, COOH, COOCH3, CONH(CH2)2NH2 are described. Comparison of the unsubstituted parent compound with the substituted compounds shows that bipyridine substitution doesn't alter significantly the photophysical properties of the lanthanide cryptate. The absorption maximum is slightly red-shifted when three bipyridines are substituted, whereas substituting one bipyridines has a negligible effect on the absorption spectra. The experimental triplet state energy is between 21600 and 22 100 cm(-1) for the series of compounds and the luminescence lifetimes at 77 K are between 0.5 and 0.8 ms in HO2 and equal to 1.7 ms in D2O. The experimental characterizations are completed by DFT and TD-DFT calculations to assess the ability of these approaches to predict absorption maxima, triplet state energies and structural parameters of lanthanide cryptates and to characterize the electronic structure of the excited states. The calculations on the unsubstituted parent and substituted compounds show that absorption maxima and lowest 3pipi* triplet state energies can be accurately determined from density functional theory (DFT) and time-dependent (TD) DFT calculations.     

One Pot Synthesis of Bisphosphonate Esters: A Way to Synthesize Tetraphosphonate Esters

Abstract

Several methods for the preparation of symmetrical bisphosphonates of general type (RO)₂P(O)(R′OH)P(O)(OR)₂, have been developed, and investigated for their pharmacological. Pharmacological screening of these bisphosphonates have shown that these compounds have potent cardiovascular activity and are. potentialy useful in the treatment of hypertension. In this work we described of new method “one pot” for the synthesis of hydroxy bis and tetra phosphonates (I, II, III and IV).