HPLC determination of irbesartan in human plasma: its application to pharmacokinetic studies

A simple and rapid HPLC method using fluorescence detection was developed for determination of irbesartan in human plasma. Sample preparation was accomplished through a simple deproteinization procedure with 0.4 mL of acetonitrile containing 800 ng/mL of losartan (internal standard), and to a 0.1 mL plasma sample. Chromatographic separation was performed on a Zorbax Xclipse XDB C₁₈ column (150 × 4.6 mm, i.d., 5 µm) at 40°C. An isocratic mobile phase, acetonitrile:0.1% formic acid (37:63, v/v), was run at a flow‐rate of 1.0 mL/min, and the column eluent was monitored using a fluorescence detector set at excitation and emission wavelengths of 250 and 370 nm, respectively. The retention times of irbesartan and losartan were 4.4 and 5.9 min, respectively. This assay was linear over a concentration range of 10–5000 ng/mL with a lower limit of quantification of 10 ng/mL. The coefficient of variation for this assay precision was less than 8.48%, and the accuracy exceeded 94.4%. The mean relative recoveries of irbesartan and losartan were 98.4 and 99.1%, respectively. This method was successfully applied for pharmacokinetic study after oral administration of irbesartan (300 mg) to 23 Korean healthy male volunteers. Copyright © 2009 John Wiley & Sons, Ltd.     

Solutions of two-factor models with variable interest rates

The focus of this work is on numerical solutions to two-factor option pricing partial differential equations with variable interest rates. Two interest rate models, the Vasicek model and the Cox–Ingersoll–Ross model (CIR), are considered. Emphasis is placed on the definition and implementation of boundary conditions for different portfolio models, and on appropriate truncation of the computational domain. An exact solution to the Vasicek model and an exact solution for the price of bonds convertible to stock at expiration under a stochastic interest rate are derived. The exact solutions are used to evaluate the accuracy of the numerical simulation schemes. For the numerical simulations the pricing solution is analyzed as the market completeness decreases from the ideal complete level to one with higher volatility of the interest rate and a slower mean-reverting environment. Simulations indicate that the CIR model yields more reasonable results than the Vasicek model in a less complete market.     

Study of Internal Linear Inductively Coupled Plasma Source for Ultra Large-Scale Flat Panel Display Processing

An internal-type linear inductive antenna, which is referred to as “double comb-type antenna”, was used as a large-area inductively coupled plasma (ICP) source with a substrate area of 2,300 mm × 2,000 mm. The characteristics of the ICP source were investigated for potential applications to flat panel display (FPD) processing. The source showed higher power transfer efficiency at higher RF power and higher operating pressures. The power transfer efficiency was approximately 88.1% at 9 kW of RF power and a pressure of 20 mTorr Ar. This source showed increasing plasma density and improved plasma uniformity with increasing RF power at a given operating pressure. A plasma density >1.5 × 10¹¹/cm³ and a plasma uniformity of approximately 11% was obtained at 9 kW of RF power and 15 mTor Ar using this internal ICP source, which is applicable to FPD processing.     

Properties of spatial cross-periodograms using fixed-domain asymptotics

Cross-periodograms can be used to study a multivariate spatial process observed on a lattice. For spatial data, it is often appropriate to study asymptotic properties of statistical procedures under fixed-domain asymptotics in which the number of observations increases in a fixed region while shrinking distances between neighboring observations. Using fixed-domain asymptotics, we prove relative asymptotic unbiasedness and relative consistency of a smoothed cross-periodogram after appropriate filtering of the data. In addition, we show that smoothed cross-periodograms are asymptotically normal when the process is stationary multivariate Gaussian with appropriate assumptions on high-frequency behavior of the spectral density.     

Effect of therapeutic ultrasound on the healing of full-thickness excised skin lesions

The effect of therapeutic ultrasound on the healing of the dermis of full-thickness excised lesions made in the flank skin of adult rats was assessed quantitatively by means of differential cell counts made in sections of the wound bed five and seven days after injury. Wounds were either sham-treated (control group) or exposed to pulsed ultrasound (2 ms on, 8 ms off) at an intensity of 0.1 W cm-2 SATA (frequency either 0.75 MHz or 3.0 MHz). By five days after injury, ultrasound-treated wounds contained more extensive granulation tissue, fewer polymorphonuclear leucocytes (polymorphs) and macrophages, and more fibroblasts (aligned in a manner conducive to efficient wound contraction) than the sham-irradiated controls. By seven days after injury there was no significant difference in cellularity between the controls and the ultrasonically-irradiated wounds. The results obtained suggest that ultrasound therapy can be useful in accelerating the inflammatory and early proliferative stages of repair.     

Valence‐to‐core X‐ray emission spectroscopy of titanium compounds using energy dispersive detectors

X‐ray emission spectroscopy (XES) of transition metal compounds is a powerful tool for investigating the spin and oxidation state of the metal centers. Valence‐to‐core (vtc) XES is of special interest, as it contains information on the ligand nature, hybridization, and protonation. To date, most vtc‐XES studies have been performed with high‐brightness sources, such as synchrotrons, due to the weak fluorescence lines from vtc transitions. Here, we present a systematic study of the vtc‐XES for different titanium compounds in a laboratory setting using an X‐ray tube source and energy dispersive microcalorimeter sensors. With a full‐width at half‐maximum energy resolution of approximately 4 eV at the Ti Kβ lines, we measure the XES features of different titanium compounds and compare our results for the vtc line shapes and energies to previously published and newly acquired synchrotron data as well as to new theoretical calculations. Finally, we report simulations of the feasibility of performing time‐resolved vtc‐XES studies with a laser‐based plasma source in a laboratory setting. Our results show that microcalorimeter sensors can already perform high‐quality measurements of vtc‐XES features in a laboratory setting under static conditions and that dynamic measurements will be possible in the future after reasonable technological developments.     

Palladium-Catalyzed Regioselective Synthesis of 3-Arylindoles from N-Ts-Anilines and Styrenes

A Pd-catalyzed intermolecular oxidative annulation between N-Ts-anilines and styrenes was developed. This method offers a straightforward and robust approach to a wide range of 3-arylindoles using readily available starting materials with good functional-group tolerance and high regioselectivity and efficiency. Further elaboration of the products obtained from this process provided access to highly functionalized and structurally diverse indoles, for example, 3-(indol-3-yl)carbazoles, 1,9-dihydropyrrolo-[2,3-b]carbazoles, and 3′-aryl-3,5′-biindoles.     

Synthesis and characterization of Rosuvastatin calcium impurity A; a HMG-CoA reductase inhibitor

During the process development for multistep synthesis of Rosuvastatin calcium several impurities were obtained along with the final Rosuvastatin calcium. Out of this; synthesis of impurity A (acetone adduct) a minor impurity of Rosuvastatin calcium (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[[(2-hydroxy-2-methylpropyl)sulfonyl(methyl)amino]-6-(1-methylethyl)-pyrimidin-5-yl]-3,5-dihydroxyheptenoicacid hemicalcium salt, is described. The synthesis of impurity A has been accomplished in 6 steps; starting from formation of β-hydroxy sulfonamide as the key intermediate and followed by using convenient routes with overall yield of 13.5%. The target compound can be used as the reference substance of impurity of the Rosuvastatin calcium.     

Tandem one-pot synthesis of α-(aminomethylene)-γ-butyrolactones via regioselective epoxide ring-opening with the Blaise reaction intermediate

A novel tandem one-pot method for the synthesis of α-aminomethylene-γ-butyrolactone derivatives has been developed through the regioselective epoxide opening reactions with the Blaise reaction intermediates, generated by the reaction of a Reformatsky reagent with nitriles. Formation of a modified Blaise reaction intermediate by the addition of a stoichiometric amount of n-BuLi followed by slow addition of epoxide is required for the good yield of γ-butyrolactones.