Development of a Simple,Rapid, and Robust Isocratic Liquid Chromatographic Method for the Determination of Pyrimethamine and its Synthetic Impurities in Bulk Drugs and Pharmaceutical Formulations

Pyrimethamine is an important antiparasitic drug in the treatment of malaria and toxoplasmosis and is often used in combination with either sulfadoxine, sulfalene, or sulfadiazine. Determining the content of pyrimethamine and investigating the related substances is currently possible applying either a compendial monograph utilizing thin layer chromatography as well as liquid chromatographic methods used by the respective manufacturers. To provide a simple method which is capable of determining the content of pyrimethamine and of resolving four of its potential synthetic impurities a very simple, cheap, precise, and accurate isocratic RP-HPLC method was developed. All analytes can be separated within a total runtime of 30 min and the method was linear within the concentration ranges of 0.12–0.740, 0.104–0.621, 0.120–0.710, 2.0–11.8, and 1.01–5.80 µg mL^?1 for pyrimethamine, impurity A, impurity B, impurity C, and impurity D, respectively. These substances were separated by employing a Eurospher-II C₁₈H column (250 × 4.6 mm, 5 µm particle size), a mobile phase being a mixture of a 0.05 M KH₂PO₄ buffer solution (pH 2.6) and methanol in the ratio 40:60 (v/v). The analysis was carried out at 30 °C, applying a flow rate of 1.2 mL min^?1, and a detection wavelength of λ = 215 nm. The coefficients of determinations (R ²) for the five analytes were greater than 0.994 for pyrimethamine and all impurities. Results of recovery studies were within the range of 89.1–105.1% for all substances. In all tested genuine batches of pyrimethamine raw material impurities within the specified limits were present which is concurrent with results obtained from using the present manufacturer’s method.     

[3+2] Cycloadditions of Metallo Nitrile Ylides and Metallo Nitrile Imines with Metal Carbonyl,Thiocarbonyl, and Isocyanide Complexes: Heterodimetallic Systems with Bridging Heterocycles [1]

The reactions of [Re(CO)₆]⁺, [FeCp(CO)₂CS]⁺ and [FeCp(CNPh)₃]⁺ with the metallo nitrile ylides [M^–{C⁺=N–C^–(H)CO₂Et}(CO)₅]^– (M = Cr, W) and the chromio nitrile imine [Cr^–{C⁺=N–N^–H}(CO)₅]^– (generated by mono‐α‐deprotonation of the parent isocyanide complexes) to give neutral 5‐metallated 1,3‐oxazolin‐ ( 1 ), 1,3‐thiazolin‐ ( 2 ), imidazolin‐ ( 3 , 4 ), 1,3,4‐oxdiazolin‐ ( 5 ), 1,3,4‐thiadiazolin‐ ( 6 ) and 1,3,4‐triazolin‐2‐ylidene ( 8 ) chromium and tungsten complexes represent the first all‐organometallic versions of Huisgen’s 1,3‐dipolar cycloadditions. The formation of 6 and 8 is accompanied by partial decomposition to (OC)₅Cr–C≡N–FeCpL₂ {L = CO ( 7 ), CNPh ( 9 )}. The structures of 4a and 5 have been characterized by X‐ray diffraction.     

Standardization in allergen determination

An overview is given of sensitization and allergic reaction on food, along with minimal eliciting doses for selected allergens (milk, egg, peanut), followed by the legislative situation in the European Community, the USA, Canada, Australia/New Zealand and Japan. The main focus of the paper discusses methods for food allergen determination (chromatography, DNA-based, antibody-based) and their limitations. Special emphasis is given on antibody-based systems, which are at the moment the most advanced and validated methods available. Examples are given of the current status of standardization for egg, milk, nuts, prolamins, glutelins and for clinical validated reference samples from the EU project EuroPrevall. Recommendations for ongoing activities are also included.     

Computational homogenization and parameter-identification for heterogeneous inelastic materials

The aim of this paper is to describe a method for identifying micro material parameters using only macroscopic experimental data. The FE² method is used to model the behavior of the complex materials with heterogeneous micro-structure. The resulting least squares problem is minimized using gradient-based optimization algorithms, where the gradient information is derived analytically within the discretized scheme. (© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

A 43Ca and 13C NMR study of the chemical interaction between poly(ethylene-vinyl acetate) and white cement during hydration

⁴³Ca and ¹³C NMR methods were used to study the chemical interaction of poly(ethylene–vinyl acetate) (PEVAc) admixture in commercial-grade white cement. From ⁴³Ca NMR it is shown both that PEVAc induces modest changes in the hydrated cement structure, and that hydrated commercial cement is significantly more complex than models that have been used for its structure in past work. The ¹³C NMR results show that the PEVAc hydrolysis occurs early in the cement hydration acceleration period, with a rate well-fit by an exponential decay using a time constant of 6±1 days.     

Operation of a Raman laser in bulk silicon

A Raman laser based on a bulk silicon single crystal with 1.127 μm emission wavelength is demonstrated. The Si crystal with 30 mm length was placed into an external cavity and pumped by a Q-switched Nd:YAG master oscillator power amplifier system. Strong defocusing of the pump and Raman laser beam by free carriers was compensated by an intracavity lens. Raman laser operation with a pulse duration of 2.5 ns was identified by a Raman laser threshold significantly lower than the single-pass stimulated Raman-scattering threshold. Linear absorption losses of the 1.06415 μm pump radiation are strongly reduced by cooling the Si crystal to a temperature of 10 K.     

A Fast and Efficient Track to Allosteric Modulators of Muscarinic Receptors: Microwave-Assisted Syntheses

By using microwave irradiation bisammonium-and bispyridinium-type allosteric modulators of muscarinic receptors can be obtained fast and efficiently.