Development and validation of an LC-ESI-MS/MS method for simultaneous quantitation of olmesartan and pioglitazone in rat plasma and its pharmacokinetic application

A simple, high‐throughput and specific high‐performance liquid chromatography tandem mass spectrometry method has been developed and validated according to the FDA guidelines for simultaneous quantification of olmesartan and pioglitazone in rat plasma. The bioanalytical method consists of liquid–liquid extraction and quantitation by triple quadrupole mass spectrometry using electrospray ionization technique, operating in multiple reaction monitoring and positive ion modes. The compounds were eluted isocratically on a C₁₈ column with a mobile phase consisting of a mixture of methanol and water (containing 0.5% formic acid) in a ratio of 9:1. The response to olmesartan and pioglitazone was linear over the range 0.01–10 µg/mL. The validation results demonstrated that the method had satisfactory precision and accuracy across the calibration range. Intra‐ and inter‐day precisions ranged from 0.66 to 3.32 and from 0.94 to 2.93% (%CV), respectively. The accuracy determined at three quality control levels was within 91.27–107.28%. There was no evidence of instability of the analytes in rat plasma following the stability studies. The method proved highly reproducible and sensitive and was successfully applied in a pharmacokinetic study after single dose oral administration of olmesartan and pioglitazone to the rat. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis of copper sulphide and copper nanoparticles with microemulsion method

The present work is focused on the synthesis of nanocopper and nanocopper sulphide metallic particles. The precise control of size and shape is best achievable with microemulsion technique, with in situ synthesis in microemulsion. The effect of most crucial operating parameter, water-to-surfactant molar ratio (w), on the product specification including size as well as size distribution and morphology were investigated. The variation of size was observed with variation in w for copper sulphide and copper. Product specifications were analyzed using transmission electron microscope imaging, dynamic light scattering with particle size analyzer and absorption spectra using UV-visible spectrophotometer. It was observed that bigger particles were achieved at higher water-to-surfactant ratio. From systematic study of effect of w on the size and size distribution of copper nanoparticles, the optimum value was chosen for preparation of in situ catalyst. As copper on alumina catalyst has wide catalytic applications of commercial importance, alumina was selected as support. A novel deposition method is developed successfully to deposit the copper nanoparticles from microemulsion on the support. Thus prepared catalyst was analyzed with UV-visible spectrophotometer and found to contain characteristic peak of copper at 655 nm, indicating proper copper deposition on support. XRD analysis of copper on alumina catalyst confirmed presence of metallic copper.     

Cigarette smoke extract induced protein phosphorylation changes in human microvascular endothelial cells in vitro

Phosphorylation is the most widely studied posttranslational modification (PTM) and is an important regulatory mechanism used during cellular responses to external stimuli. The kinases and phosphatases that regulate protein phosphorylation are known to be affected in many human diseases. Cigarette smoking causes cardiovascular disease (CVD). Endothelial cells play a pivotal role in CVD initiation and development; however, there have been limited investigations of the specific signaling cascades and protein phosphorylations activated by cigarette smoke in endothelial cells. The purpose of this research was to better understand the differential protein phosphorylation in endothelial cells stimulated with extracts of cigarette smoke total particulate matter (CS-TPM) in vitro. Human microvascular endothelial cells were exposed in vitro to CS-TPM at concentrations that were shown to cause endothelial cell dysfunction. The phosphorylated proteins were isolated using phosphoprotein-specific chromatography, followed by enzymatic digestion and nano-flow capillary liquid chromatography (ncap-LC) coupled to high resolution mass spectrometry. This study putatively identified 94 proteins in human microvascular endothelial cells that were differentially bound to a phosphoprotein-specific chromatography column following exposure to CS-TPM suggesting differential phosphorylation. Pathway analysis has also been conducted and confirmations of several observations have been made using immunoaffinity-based techniques (e.g., Western blotting). Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Spectral interference study of uranium on other analytes by using CCD based ICP-AES

Due to the multi-electronic nature, uranium is having line rich emission spectra and is expected to interfere during the determination of analytes at the trace level in uranium matrix. Therefore, chemical separation of uranium followed by the determination of trace metallic impurities in the raffinate by ICP-AES is generally adopted procedure in nuclear industries. There is restriction on choosing alternate analytical lines of elements by photomultiplier tube based ICP-AES associated with the polychromator while monochromator needs significant time to scan different analytical lines of all the elements. Since charged coupled detector (CCD) consists of array of pixels, it is having more option in choosing alternative analytical lines of the analytes. Therefore, an attempt was made to study the spectral interference of uranium on different analytical lines of analytes viz. Al, Ga, In, Si, Li, Ti, Mg, Sr, K, Ce, Nd, Lu, Sc, V, Er, Y, Ba, Bi, Pb, W, La, Tl, Sn, Yb, Mo, Sb, Pr and Zr; and the correction factors were evaluated (where ever necessary) using CCD based ICP-AES technique. The sensitivity and the detection limits of the analytical channels of the elements in presence of uranium matrix were calculated. The present study also deals with the identification of suitable analytical lines of uranium and its detection limits.     

Synthesis of silver nanoparticles in an aqueous suspension of graphene oxide sheets and its antimicrobial activity

A solution-based approach to the synthesis of silver (Ag) nanoparticles by chemical reduction of AgNO(3) in a graphene oxide (GrO) suspension is demonstrated. X-ray diffraction and transmission electron microscopy indicate that the Ag nanoparticles, of size range 5-25nm, were decorated on the GrO sheets. The size and shape of the Ag nanoparticles are dependent on the concentration of the AgNO(3) solution. Antimicrobial activity of such hybrids materials is investigated against the Gram negative bacteria Escherichia coli and Pseudomonous aeruginosa. The bacterial growth kinetics was monitored in nutrient broth supplemented with the Ag nanoparticle-GrO suspension at different conditions. It was observed that P. aeruginosa is comparatively more sensitive to the Ag nanoparticle-GrO suspension.     

Intermolecular cross-double-michael addition between nitro and carbonyl activated olefins as a new approach in C-C bond formation

A novel intermolecular cross-double-Michael addition between nitro and carbonyl activated olefins has been developed through Lewis base catalysis. The reaction took place with a large group of beta-alkyl nitroalkenes and alpha,beta-unsaturated ketone/esters, producing an allylic nitro compound in good to excellent yields.     

Synthesis,Structures, and Fungitoxicity of Novel Organophosphorus Compounds

Abstract

A series of biologically active organophosphorus compounds have been synthesized by the reactions of O,O-diethylchlorophosphate with Schiff bases derived from 5-(phenyl/substituted phenyl)-2-hydrazino-1,3,4-oxadiazole and salicylaldehyde/2-hydroxyacetophenone. The compounds have been characterized on the basis of analyses and spectral (IR, ¹H, ¹³C NMR) data. Fungicidal activities of these derivatives against Colletotrichum falcatum, Fusarium oxysporum, and Curvularia pallescence have been evaluated. All compounds showed moderate to significant antifungal activity.     

Late stage modification of peptides via CH activation reactions

Recently developed strategies for late stage modification of peptides through CH activation, an arena of contemporary interest in chemical biology and drug discovery, are discussed. Through this tactic, non-polar amino acids in peptides have been selectively functionalized and CH activation enabled new CC and CX bond formations (arylation, alkynylation, fluorination, hydroxylation, azidation, etc.) are documented. Significant advances have been made in Pd or Au-catalyzed, racemization-free, tryptophan specific modifications of large peptides via CH arylation and alkynylation reactions without any protecting group requirement. Development of a new biaryl stapling technique for complex peptides, 18F radiofluorine introduction and diversity oriented post synthetic applications on bio-active cyclopeptides like valinomycin and aureobasidin are additional highlights which underscores the vast potential of late stage CH activation reactions in peptide based therapeutics research.     

Solvent dependent analysis of isotropic Raman band shape of C=O stretching vibration

The isotropic Raman band shape corresponding to C=O stretching vibration of some molecules has been studied in neat liquids and as a function of solvent concentration using both polar and non-polar solvents. The Raman band shape was analyzed on the basis of correlation with the Lorentzian line shape by employinga simple method of linear curve fitting. In neat liquids and in low solvent concentration region, the band shape was found to be non-Lorentzian. With the gradual increase in solvent concentration the band shape approaches a Lorentzian function. The plot of the correlation coefficient for a Lorentzian shape shows a discontinuity in the intermediate range of solvent concentration. The influence of the structural characteristics of the solute and the solvent systems on the reference mode and various multipolar interactions together with the time varying spatial distribution of solvent molecules with respect to the reference molecule are expected to govern the microenvironmental fluctuations. This may be responsible for the discontinuity in the intermediate solvent concentration region.