The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds

A post-column infusion system was developed in order to analyze suppression of electrospray ionization (ESI) tandem mass spectrometry response in the presence of endogenous plasma interferences. By enabling direct detection of these interfering components, this experimental system was used to analyze the ability of several common extraction procedures to remove endogenous plasma components that cause changes in the ESI response of model drug substances. Methyl-t-butyl ether (MTBE) liquid-liquid, Oasis and Empore solid-phase, and acetonitrile (ACN) protein precipitation sample preparation methods were tested using the post-column infusion system. In all cases, ACN protein precipitation samples showed the greatest amount of ESI response suppression while liquid-liquid extracts demonstrated the least. In addition, the three test compounds, phenacetin, caffeine, and a representative Merck compound, demonstrated that ESI response suppression is compound dependent. Suppression was greatest with caffeine, the most polar analyte, and the smallest for the Merck compound, the least polar analyte. Copyright 1999 John Wiley & Sons, Ltd.     

Gamma-ray spectroscopy with relativistic exotic heavy-ions

Feasibility of gamma-ray spectroscopy at relativistic energies with exotic heavy-ions and new generation of germanium detectors (segmented Clover) is discussed. An experiment with such detector array and radioactive is discussed.     

Percolative transport in the vicinity of charge-order ferromagnetic transition in a hole-doped manganite

We report measurements of non-linear charge transport in epitaxial (La_1−x Pr _x )_0.7Ca_0.3MnO₃ thin films fabricated on (100) oriented SrTiO₃ single crystals by pulsed laser deposition. The end members of this series, namely Pr_0.7Ca_0.3MnO₃ and La_0.7Ca_0.3MnO₃ are canonical charge-ordered (CO) and ferromagnetic manganites, respectively. The onset of the CO state in Pr_0.7Ca_0.3MnO₃ is manifested by a pronounced insulating behavior below ∼ 200 K. The CO state remains stable even when a large (∼ 2×10⁵ V/cm) electric field is applied across the thin film samples. However, on substitution of Pr with La, a crossover from the highly resistive CO state to a state of metallic character is observed at relatively low electric fields. The current-voltage characteristics of the samples at low temperatures show hysteretic and history dependent effects. The electric field driven charge transport in the system is modelled on the basis of an inhomogeneous medium consisting of ferromagnetic metallic clusters dispersed in a CO background.     

Chitosan nanoparticles of 5-fluorouracil for ophthalmic delivery: characterization, in-vitro and in-vivo study

The aim of this investigation was to develop 5-fluorouracil (5-FU) loaded chitosan nanoparticles (CH-DNPs) for ophthalmic delivery. CH-DNPs were fabricated by ionotropic gelation mechanism using chitosan (CH) and a polyanion (TPP). The nanoparticles were smooth and spherical, confirmed by scanning electron microscopy (SEM) and atomic force microscope (AFM). CH/TPP mass ratio and TPP significantly changed the particles size morphology and encapsulation efficiency. The nanoparticles size ranged from approximately 114 to 192 nm and had a positive zeta potential (30±4 mV). The encapsulation efficiency, loading capacity and recovery of DNPs were 8.12-34.32%, 3.14-15.24% and 24.22 to 67% respectively. Physical characterization was done by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). No interaction was observed in between drug and polymer and crystallinity of drug was not changed in drug loaded nanoparticles. In-vitro release study of DNPs showed diffusion controlled release. Bioavailability study of batch CS9 was studied in rabbit eye and compare to 5-FU solution. 5-FU level was significantly higher in aqueous humor of rabbit eye. Ocular tolerance was studied in the eye of New Zealand rabbits and tested formulation was non-irritant with no sign of inflammation.     

Self-chemical ionization of diethylzinc

The self-chemical ionization of diethylzinc is examined by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry and semiempirical molecular orbital calculations. Electron impact of diethylzinc neutral produces the radical cation, C(4)H(15)Zn(+) (m/z x 122), which reacts further with the neutral (C(2)H(5))(2)Zn to give the following product ions: Zn(+) (m/z x 64), C(2)H(5)Zn(+) (m/z x 93), C(4)H(9)Zn(+) (m/z x 121), C(4)H(11)Zn(2)(+) (m/z x 187), and C(6)H(15)Zn(2)(+) (m/z x 215). To determine the structure and pathways for production of these ions, monoisotopic (12)C(4)H(15)(64)Zn(+), (64)Zn(+) and (12)C(2)H(5)(64)Zn(+) were individually isolated and reacted with the neutral background. We also performed semiempirical molecular orbital calculations (ZINDO/1). The molecular orbital calculations and experimental data are consistent in predicting that the ethyl group on the diethylzinc cation carries the positive charge. Copyright 1999 John Wiley & Sons, Ltd.     

Modified PLA nano in situ gel: a potential ophthalmic drug delivery system

A novel nano in situ gel forming system of 5-Fluorouracil (5-FU) was investigated for its potential use for conjunctival/corneal squamous cell carcinoma (CCSC). The study was conducted in two steps, in the first step PLA nanoparticles were prepared and characterized; in the second step the drug loaded PLA nanoparticles were dispersed in sodium alginate solution yielding the modified nano in situ system, which were evaluated in rabbit eye. Size and morphology of prepared PLA particles were verified by using dynamic light scattering (DLS), atomic force microscope (AFM) and scanning electron microscope (SEM). In vitro and in vivo study of free 5-FU, PLA nanoparticles and modified nano in situ system were conducted in simulated tear fluid and in rabbit eye respectively. PLA nanoparticles were in size range of 128-194 nm with spherical shape and smooth surface with narrow size distribution. No polymer drug interaction was found as confirmed by FTIR, NMR and DSC. XRD of PLA nanoparticles confirmed that 5-FU was present in the crystalline state. In vitro experiments indicated a diffusion controlled release of 5-FU from both PLA nanoparticles and modified nano in situ system with high burst effect. Modified nano in situ gel system (MNS) significantly increased the Cmax and AUC0-8 in aqueous humor as compared to 5-FU solution and PLA nanoparticles. Higher 5-FU level in aqueous humor was possibly because of increased retention time of gel matrix-embedded drug loaded nanoparticles. Overall results showed the potential of MNS for ophthalmic delivery in the therapy of CCSC.     

Evidence for the quantum birth of our universe

We present evidence for a nonsingular origin of the Universe with intial conditions determined by quantum physics and relativistic gravity. In particular, we establish that the present temperature of the microwave background and the present density of the Universe agree well with our predictions from these intial conditions, after evolution to the present age using the Einstein-Friedmann equation. Remarkably, the quantum origin for the Universe naturally allows its evolution at exactly the critical density. We also discuss the consequences of these results to some fundamental aspects of quantum physics in the early Universe.     

Lomustine loaded chitosan nanoparticles: characterization and in-vitro cytotoxicity on human lung cancer cell line L132

The aim of this work was to prepare chitosan nanoparticles loaded with antineoplastic drug Lomustine (LCNPs), by ionic-gelation method with homogenization. The nanoparticles were characterized for particle size, polydispersity index (PDI), surface morphology, encapsulation efficiency, in-vitro drug release and cytotoxicity on human lung cancer cell line L132 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The particle size, zeta potential and encapsulation efficiency of prepared nanoparticles ranged from 75 ± 1.1 to 637 ± 1.6 nm (PDI from 0.05 ± 0.001 to 0.18 ± 0.007), 37.2 ± 0.21 to 53.8 ± 0.18 mV and 66.74 ± 1.4 to 98.0 ± 1.8% respectively. The particles were spherical in shape with smooth surface in scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images. Mechanical shearing by homogenization treatment significantly changed the nanoparticle size. The drug release rate was biphasic and diffusion controlled over the 8 h. LCNPs greatly inhibited the growth of the L132 cancer cell line used in this study in comparison to the native Lomustine (LMT).