Sensitive liquid chromatographic/tandem mass spectrometric method for the determination of beclomethasone dipropionate and its metabolites in equine plasma and urine

Beclomethasone dipropionate (BDP) is a potent pro-drug to beclomethasone (BOH) and is used in the treatment of chronic and acute respiratory disorders in the horse. The therapeutic dose of BDP (325 microg per horse) by inhalation results in very low plasma and urinary concentrations of BDP and its metabolites that pose a challenge to detection and confirmation by equine forensic laboratories. To solve this problem, a method involving the use of a liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) was developed for the detection, confirmation and quantification of the analytes in equine samples. Ammonium formate or acetate buffer added to LC mobile phase favored the formation of [M + H](+) ions from BDP and its metabolites, whereas formic acid led to the formation of sodium and potassium adduct ions ([M + Na](+), [M + K](+)) together with [M + H](+) ions. Acetonitrile, on the other hand, favored the formation of abundant solvent adduct ions [M + H + CH(3)CN](+) with the analytes under electrospray ionization (ESI) and atmospheric pressure chemical ionization conditions. In contrast, methanol formed much less solvent adduct ions than acetonitrile. The solvent adduct ions were thermally stable and could not be completely desolvated under the experimental conditions, but they were very fragile to collision-induced dissociation (CID). Interestingly, these solvent adduct ions were observed on a triple-quadrupole mass spectrometry but not on an ion trap instrument where helium used as a damping gas in the ion trap might cause the solvent adduct ions desolvated by collision. By CID studies on the [M + H](+) ions of BDP and its metabolites, their fragmentation paths were proposed. In equine plasma at ambient temperature over 2 h, BDP and B21P were hydrolyzed in part to B17P and BOH, respectively, but B17P was not hydrolyzed. Sodium fluoride added to equine plasma inhibited the hydrolysis of BDP and B21P. The matrix effect in ESI was evaluated in equine plasma and urine samples. The method involved the extraction of BDP and its metabolites from equine plasma and urine samples by methyl tert-butyl ether, resolution on a C(8) column with a mobile phase gradient consisting of methanol and ammonium formate (2 mmol l(-1), pH 3.4) and multiple reaction monitoring for the analytes on a triple-quadrupole mass spectrometer. The detection limit was 13 pg ml(-1) for BDP and B17P, 25 pg ml(-1) for BOH and 50 pg ml(-1) for B21P in plasma and 25 pg ml(-1) for BOH in urine. The method was successfully applied to the analysis of equine plasma and urine samples for the analytes following administration of BDP to horses by inhalation. B17P, the major and active metabolite of BDP, was detected and quantified in equine plasma up to 4 h post-administration by inhalation of a very low therapeutic dose (325 microg per horse) of BDP.     

Stability and instability of a hot and dilute nuclear droplet

The diabatic approach to dissipative collective nuclear motion is reformulated in the local-density approximation in order to treat the normal modes of a spherical nuclear droplet analytically. In a first application the adiabatic isoscalar modes are studied and results for the eigenvalues of compressional (bulk) and pure surface modes are presented as function of density and temperature inside the droplet, as well as for different mass numbers and for soft and stiff equations of state. We find that the region of bulk instabilities (spinodal regime) is substantially smaller for nuclear droplets than for infinite nuclear matter. For small densities below 30% of normal nuclear matter density and for temperatures below 5 MeV all relevant bulk modes become unstable with similar growth rates. The surface modes have a larger spinodal region, reaching out to densities and temperatures way beyond the spinodal line for bulk instabilities. Essential experimental features of multifragmentation, like fragmentation temperatures and fragment-mass distributions (in particular the power-law behavior) are consistent with the instability properties of an expanding nuclear droplet, and hence with a dynamical fragmentation process within the spinodal regime of bulk and surface modes (spinodal decomposition). Received: 4 September 2000 / Accepted: 14 November 2000     

Syntheses,characterization and crystal structures of two square-planar Ni(II) complexes with unsymmetrical tridentate Schiff base ligands and monodentate pseudohalides

Two new square-planar Ni(II) complexes, [NiL¹(NCS)] (1) and [NiL²(N₃)] (2) have been synthesized with the unsymmetrical tridentate Schiff base ligands [(CH₃)₂NCH₂CH₂N=C(CH₃)CH=C(OH)(C₆H₅)], L ¹ H, derived from benzoylacetone and 2-dimethylaminoethylamine and [(CH₃CH₂)₂NCH₂CH₂N=C(CH₃)CH=C(OH)(C₆H₅)], L ² H, derived from benzoylacetone and 2-diethylaminoethylamine, respectively. The complexes have been characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, electrochemical and thermal methods (where applicable). Structures have been established by the single-crystal X-ray diffraction technique which reveals the discrete nature of the complexes in which the metal centers adopt a distorted square planar geometry. Coordination environments of the metal ions in the complexes are satisfied with two different unsymmetrical Schiff base ligands having similar N₂O donor sets and a terminal pseudohalide anion (thiocyanate for 1 and azide for 2).     

Anhydrous state proton conduction in sulfonated bisphenol a polyetherimide with 1H‐1,2,4 triazole as proton solvent

In this study, bisphenol A polyetherimide was sulfonated to various degrees (22, 48, and 62%) by trimethylsilylchlorosulfonate (TMSCS). Novel anhydrous proton conducting polyelectrolytes were prepared by the incorporation of 1H‐1,2,4‐triazole (Taz) as proton solvent in sulfonated polyetherimide (SPEI) matrix. The conductivity reached about 2 × 10^–3 S/cm at 80 °C and 10^–2 S/cm at 140 °C. The temperature dependence proton conductivity of the polyelectrolytes followed Arrhenius equation. The conductivity improved considerably at a temperature close to the triazole melting temperature in SPEI(X)H matrix. It was proposed that the high mobility of the triazolium ions (vehicle diffusion), in addition to structure diffusion, contribute to the high conductivity of these proton conducting electrolytes above the melting temperature of triazole. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 2178–2187, 2009     

Three-Potential Formalism for the Atomic Three-Body Problem

Based on a three-potential formalism we propose mathematically well-behaved Faddeev-type integral equations for the atomic three-body problem and describe their solutions in Coulomb-Sturmian space representation. Although the system contains only long-range Coulomb interactions these equations allow us to reach a solution by approximating only some auxiliary short-range potentials. We outline the method for bound states and demonstrate its power in benchmark calculations. We can report a fast convergence in angular-momentum channels. Received September 30, 1997; accepted in final form January 23, 1998     

Tetrahedral-site vs hexagonal-site self-interstitial in silicon

The self-interstitial in silicon is studied as function of its position in between the tetrahedral and the hexagonal sites with the large-unit-cell pseudopotential method. The energy level scheme of the impurity stems from the interaction between the atomic orbitals of the interstitial and nearest-neighbour host crystal bonding orbitals. The striking changes in electronic structure along the path are not due to a variation of the impurity potential but rather to that of the host crystal environment.     

Reasonable synthesis of alpha-L-homoproline and some derivatives. Preparation of 7-alpha-L-homoproline-bradykinin]

Optically pure α-L -homoproline can be prepared with good yield from N-bnezyloxycarbonyl-L -proline through its diazoketone-derivative. Preparation of derivatives of α-L -homoproline used in peptide chemistry, and of 7-α-L -homoproline-bradykinin, as well as biological investigation of the latter are described.     

Year by Year Changes of Indoor Radon Levels

Short-term fluctuations of indoor radon may occur due to weather conditions, seismic activity etc. These average out during the year. According to our measurements, in the very same room the yearly average of radon concentration may also change by 25–50% from year to year. This observation may make the comparison of indoor radon levels of houses measured in different years unjustified; large scale radon maps based upon such data are less reliable. Possible causes of such year-by-year changes are discussed empirically. The conclusions may be helpful to foresee long-term tendencies, implied by changes of living habits and by climatic shifts.     

Binding mechanism of RGD and its mimetics to receptor GPIIb/IIIa. A theoretical study

In order to better understand, at a sub-molecular level, the minimal structural requirements for the recognition process in the platelet aggregation inhibitory activity, a series of RGD mimetics were examined as fibrinogen receptor antagonists variants. We simulate the electronic interactions between RGD with its biological receptor in terms of smaller molecules. MeCOO⁻ was used to mimic the side chain of deprotonated Asp and Meguanidinium group mimicked the side chain of the protonated Arg. Alternative moieties present on the RGD mimetics were also studied in this report. AM1; RHF/3-21G; B3LYP/6-31++G^** in the gas phase. Also, B3LYP/6-31++G^** calculations using the IPCM solvation model were carried out for all the complexes. Our results indicate that high level of theory calculations and the inclusion of solvent effects are crucial in order to obtain satisfactory of accuracy in the electronic distributions of these compounds.