Development and validation of a stereoselective HPLC method for the determination of the in vitro transport of nateglinide enantiomers in rat intestine

A simple stereoselective high performance liquid chromatographic method was developed for the determination of the in vitro transport of the enantiomers of nateglinide (N-(trans-4-isopropylcyclohexyl-carbonyl)-phenylalanine) in the rat intestine using a Chiralcel OJ-RH column (150 x 4.0 mm, 5 microm). The effects of the mobile phase composition, pH, the flow rate, and the temperature on the chromatographic separation were investigated. The enantioseparation was achieved at 33 degrees C using a mobile phase containing 100 mM potassium dihydrogen phosphate, pH 2.5, and ACN (32:68 v/v) delivered at a flow rate of 1 mL/min. The analytes were monitored at 210 nm and linearity (r >0.99) was obtained for a concentration range of 0.5-50 microg/mL. The LOD and LOQ were 0.2 and 0.5 microg/mL for the R-enantiomer and 0.2 and 0.8 microg/mL for the S-enantiomer, respectively. Both, the intra- and interday accuracy and precision of the calibration curves were determined. The method was successfully applied to estimate the in vitro passage of the enantiomers and the racemate of nateglinide in duodenum, jejunum, and ileum of rats. Generally, higher concentrations of nateglinide and the S-enantiomer were observed when the racemate was administered compared to administration of the individual enantiomers of nateglinide.     

Development of a high-performance liquid chromatography method for simultaneous determination of pioglitazone and felodipine in pig serum: application to pharmacokinetic study

A simple and sensitive high‐performance liquid chromatographic method was developed and validated for simultaneous estimation of pioglitazone and felodipine in pig serum. The present method consists of protein precipitation, extraction of analytes from pig serum into dichloromethane and separation using reversed‐phase C₁₈ column. Nitrendipine was used as an internal standard and the eluent was monitored by UV detector at 240 nm. The mobile phase used was acetonitrile and 50 mm ammonium acetate buffer at a flow rate of 1 mL/min. The retention times for pioglitazone, felodipine and nitrendipine were found to be 5.12, 10.53 and 7.14 min, respectively. The intraday and inter‐day coefficient of variation and percent error values of assay method were less than 7% and mean recovery was more than 94% for each analyte, and the method was found to be precise, accurate and specific during study. The method was successfully applied for pharmacokinetic study of pioglitazone and felodipine from bioadhesive buccal tablet after buccal administration to pigs. The C_Max, T_Max, and AUC_0–24 of pioglitazone and felodipine from buccal tablet were found to be 394.6 ng/mL, 5.6 h, 2624.2 ng h/mL and 44.4 ng/mL, 5.5 h, 275.8 ng h/mL, respectively. Copyright © 2010 John Wiley & Sons, Ltd.     

Monomials, binomials and Riemann–Roch

The Riemann–Roch theorem on a graph G is related to Alexander duality in combinatorial commutative algebra. We study the lattice ideal given by chip firing on G and the initial ideal whose standard monomials are the G-parking functions. When G is a saturated graph, these ideals are generic and the Scarf complex is a minimal free resolution. Otherwise, syzygies are obtained by degeneration. We also develop a self-contained Riemann–Roch theory for Artinian monomial ideals.     

Studies on decontamination of spent ion exchange resin used for plutonium purification in PUREX stream

This paper deals with the studies on decontaminations of spent ion exchange resin used for purification of plutonium in PUREX process stream. Studies were carried out to optimize the chemical procedure for removal of plutonium and fission products activities form spent Ion Exchange resin. Different metal complexing reagents were tested for leaching out of radionuclides entrapped in irradiated spent ion exchange resin. The experimental results indicate that 0.01 M NaF solution was found the most suitable for removal of plutonium. The mixture of Na₂CO₃ and sodium salt of EDTA solution was found to be better for decontamination of spent ion exchange resin from beta and gamma activities. Optimized mixture of 0.5 M Na₂CO₃ and 0.1 M sodium salt of EDTA solution was found to be the most effective for fission product activities removal. After successive multiple contacts using these suitable reagents, the Pu and fission product activities in spent ion exchange resin were brought down to a minimum possible level, making it quite suitable for its long term storage.     

Microwave-sintered Pr<Superscript>3+</Superscript>, Sm<Superscript>3+</Superscript>, and Gd<Superscript>3+</Superscript> triple-doped ceria electrolyte material for IT-SOFC applications

The Pr³⁺, Sm³⁺, and Gd³⁺ triple-doped ceria Ce_0.76Pr_0.08Sm_0.08Gd_0.08O_2-δ material as solid electrolyte for IT-SOFC has been successfully synthesized by sol–gel auto-combustion route. The effect of microwave sintering (1300 °C for 15, 30, and 60 min, named as PSG-MS15, PSG-MS30, and PSG-MS60, respectively) on structural, electrical, and thermal properties of prepared electrolyte material has been studied. Powder X-ray diffraction, scanning electron microscope, energy dispersive spectroscopy, and Raman analysis revealed the single phase, microstructure, elemental confirmation, and structural oxygen vacancy formation of all the samples. Impedance spectroscopy analysis revealed the highest total ionic conductivity, i.e., 3.47 × 10^?2 S cm^?1 at 600 °C with minimum activation energy of 0.69 eV, in PSG-MS30 sample when compared to PSG-MS15 and PSG-MS60. The thermal expansion measurements have been carried out for PSG-MS30 specimen. The highest total ionic conductivity with minimum activation energy and moderate thermal expansion coefficient of PSG-MS30 sample makes the possibility of its use as solid electrolyte in IT-SOFC applications.     

Controlling the Substrate Specificity of an Enzyme through Structural Flexibility by Varying the Salt-Bridge Density

Many enzymes, particularly in one single family, with highly conserved structures and folds exhibit rather distinct substrate specificities. The underlying mechanism remains elusive, the resolution of which is of great importance for biochemistry, biophysics, and bioengineering. Here, we performed a neutron scattering experiment and molecular dynamics (MD) simulations on two structurally similar CYP450 proteins; CYP101 primarily catalyzes one type of ligands, then CYP2C9 can catalyze a large range of substrates. We demonstrated that it is the high density of salt bridges in CYP101 that reduces its structural flexibility, which controls the ligand access channel and the fluctuation of the catalytic pocket, thus restricting its selection on substrates. Moreover, we performed MD simulations on 146 different kinds of CYP450 proteins, spanning distinct biological categories including Fungi, Archaea, Bacteria, Protista, Animalia, and Plantae, and found the above mechanism generally valid. We demonstrated that, by fine changes of chemistry (salt-bridge density), the CYP450 superfamily can vary the structural flexibility of its member proteins among different biological categories, and thus differentiate their substrate specificities to meet the specific biological needs. As this mechanism is well-controllable and easy to be implemented, we expect it to be generally applicable in future enzymatic engineering to develop proteins of desired substrate specificities.     

Fractional Fourier transform based image multiplexing and encryption technique for four-color images using input images as keys

A digital technique for multiplexing and encryption of four RGB images has been proposed using the fractional Fourier transform (FRT). The four input RGB images are first converted into their indexed image formats and subsequently multiplexed into a single image through elementary mathematical steps prior to the encryption. The encryption algorithm uses two random phase masks in the input- and the FRT domain, respectively. These random phase masks are especially designed using the input images. As the encryption is carried out through a single channel, the technique is more compact and faster as compared to the multichannel techniques. Different fractional orders, the random masks in input-, and FRT domain are the keys for decryption as well as de-multiplexing. The algorithms to implement the proposed multiplexing-, and encryption scheme are discussed, and results of digital simulation are presented. Simulation results show that the technique is free from cross-talk. The performance of the proposed technique has also been analyzed against occlusion, noise, and attacks using partial windows of the correct random phase keys. The robustness of the technique against known-, and chosen plain-text attacks has also been explained.     

Dielectric Study of the Miscibility of Binary Liquids, One Being an Alcohol

A dielectric relaxation study has been made over a frequency range of 10⁶–10^–3 Hz in the supercooled liquid state of the binary mixtures of 2-ethyl-1-hexanol (2EHOH) with a wide variety of common liquids. Differential scanning calorimetry measurements have also been made above 100 K. Our studies show compatibility of the methylcyclohexane with 2EHOH over the entire composition range. However, in the case of 1-bromobutane and acetone with 2EHOH, we have clearly seen two liquidlike phases separating out, which indicates incompatibility. In the case of 4-methyl-2-pentanol, the binary liquid shows no heterogeneity over most of the concentration range. In the case of methyl alcohol (MOH), the binary liquid shows some heterogeneity at a molecular level in the MOH-rich region. An attempt has been made to understand miscibility in terms of the preference for ring and chain formation among the alcohol molecules.     

Molecular magnetic properties of two-copper(II) containing complexes [Cu(II) (1-phenylamidino-O-n-butylurea) en (H2O)]2(2+) and [Cu(II) sulphato-mono (1-phenylamidino-O-methylurea)]2. An EPR study

Electron paramagnetic resonance (EPR) investigations were conducted on [Cu(II) (1-phenylamidino-O-n-butylurea) en (H2O)]2(2+) (1) and [Cu(II) sulphato-mono (1-phenylamidino-O-methylurea)]2 (2) respectively, in the temperature range 300-77K. Fine structure characteristics of S = 1 system, was observed in both complexes with zero field splitting of 0.0525 and 0.0225 cm(-1), respectively, suggesting the formation of dimeric complexes. The presence of the half-field signal (DeltaMs= +/-2), in the complex 1, further confirmed the formation of dimer. The temperature dependence of EPR signal intensity has given evidence for the ferromagnetic (FM) coupling between the two Cu2+ ions. The isotropic exchange interaction constants J, were evaluated from this and were found out to be approximately 57 and approximately 27 cm(-1), respectively, for the complexes 1 and 2. The photoacoustic spectra of these complexes had shown a band around 26,400 cm(-1) characteristic of metal-metal bonding giving an independent support for the existence of dimeric Cu2+ species. The high magnetic moment values at room temperature for complex 1 (2.68 microB) and complex 2 (2.00 microB), obtained from the magnetic susceptibility measurements, support the formation of ferromagnetically coupled Cu2+ dimers.