Simultaneous Determination of Losartan Potassium, Atenolol and Hydrochlorothiazide in Pharmaceutical Preparations by Stability-Indicating UPLC

A stability-indicating UPLC method was developed for the simultaneous quantitative determination of losartan potassium, atenolol, and hydrochlorothiazide in pharmaceutical dosage forms in the presence of degradation products. The separation was achieved on a simple isocratic method (water: acetonitrile: triethyl amine: ortho phosphoric acid (60:40:0.1:0.1, v/v) at 0.7 mL min^?1, a detection wavelength of 225 nm). The retention times of losartan potassium, atenolol, and hydrochlorothiazide were 2.3, 0.6 and 0.9 min. The total runtime was 3 min. Losartan potassium, atenolol, and hydrochlorothiazide were subjected to different ICH prescribed stress conditions. The method was validated with respect to linearity, accuracy, precision, robustness and ruggedness.     

DNA-Binding and cytotoxicity of the cobalt(III) ethylenediamine pyrazole complex [Co(en)2(pyz)2]3+

The complex of cobalt(III) ethylenediamine was synthesized, isolated and characterized by UV-Vis, IR, and 1H NMR spectral methods. The binding of the complex with calf thymus DNA was investigated by absorption and emission spectroscopy, viscosity measurements, DNA melting and DNA photocleavage. The spectroscopic studies together with the viscosity measurements and DNA melting studies indicated that the complex binds to calf thymus DNA in a nonintercalative mode. This complex is found to promote photocleavage of the DNA plasmid pBR322 and shows a cytotoxic effect against CHO cells.     

Synthesis of c-17 trans β-lactams of the androstane series

3,3′-Ethylenedioxyandrost-4-en-17β-ol 1 was converted into the ethyl ester 2 by reaction with potassium metal and ethyl chloroacetate. The ethyl ester 2 on reaction with hydrazine gave the hydrazide 3 . Condensation of 3 with aryl aldehydes gave the Schiff bases 4 . The reaction of Schiff bases 4 with mono-chloroacetyl chloride in the presence of triethylamine afforded the β-lactams 5 .     

Base-Catalyzed Dehydration of 3-Substituted Benzene cis-1,2-Dihydrodiols: Stabilization of a Cyclohexadienide Anion Intermediate by Negative Aromatic Hyperconjugation

Evidence that a 1,2-dihydroxycyclohexadienide anion is stabilized by aromatic "negative hyperconjugation" is described. It complements an earlier inference of "positive" hyperconjugative aromaticity for the cyclohexadienyl cation. The anion is a reactive intermediate in the dehydration of benzene cis-1,2-dihydrodiol to phenol. Rate constants for 3-substituted benzene cis-dihydrodiols are correlated by σ(-) values with ρ = 3.2. Solvent isotope effects for the reactions are k(H(2)O)/k(D(2)O) = 1.2-1.8. These measurements are consistent with reaction via a carbanion intermediate or a concerted reaction with a "carbanion-like" transition state. These and other experimental results confirm that the reaction proceeds by a stepwise mechanism, with a change in rate-determining step from proton transfer to the loss of hydroxide ion from the intermediate. Hydrogen isotope exchange accompanying dehydration of the parent benzene cis-1,2-dihydrodiol was not found, and thus, the proton transfer step is subject to internal return. A rate constant of ～10(11) s(-1), corresponding to rotational relaxation of the aqueous solvent, is assigned to loss of hydroxide ion from the intermediate. The rate constant for internal return therefore falls in the range 10(11)-10(12) s(-1). From these limiting values and the measured rate constant for hydroxide-catalyzed dehydration, a pK(a) of 30.8 ± 0.5 was determined for formation of the anion. Although loss of hydroxide ion is hugely exothermic, a concerted reaction is not enforced by the instability of the intermediate. Stabilization by negative hyperconjugation is proposed for 1,2-dihydroxycyclohexadienide and similar anions, and this proposal is supported by additional experimental evidence and by computational results, including evidence for a diatropic ("aromatic") ring current in 3,3-difluorocyclohexadienyl anion.     

Plant Growth Promotion by an Extracellular HAP-Phytase of a Thermophilic Mold <Emphasis Type="Italic">Sporotrichum thermophile</Emphasis>

Phytase of the thermophilic mold Sporotrichum thermophile Apinis hydrolyzed and liberated inorganic phosphate from Ca⁺², Mg⁺², and Co⁺² phytates more efficiently than those of Al³⁺, Fe²⁺, Fe³⁺, and Zn²⁺. The hydrolysis rate was higher at 60 °C as compared to 26 °C. Among all the organic acids tested, citrate was more effective in enhancing solubilization of insoluble phytate salts by phytase than others. The dry weight and inorganic phosphate contents of the wheat plants were high when supplemented with phytase or fungal spores. The plants provided with 5 mg phytate per plant exhibited enhanced growth and inorganic phosphate. With increase in the dosage of phytase, there was increase in growth and inorganic phosphate of plants, the highest being at 20 U per plant. The compost made employing the combined native microflora of the wheat straw and S. thermophile promoted growth of the plants. The plant-growth-promoting effect was also higher with the compost made using S. thermophile than that from only the native microflora.     

Synthesis and characterization of positively charged pentacationic [60]fullerene monoadducts for antimicrobial photodynamic inactivation

We designed and synthesized two analogous pentacationic [60]fullerenyl monoadducts, C??(>ME?N??C?) (1) and C??(>ME?N??C?) (2), with variation of the methoxyethyleneglycol length. Each of these derivatives bears a well-defined number of cationic charges aimed to enhance and control their ability to target pathogenic Gram-positive and Gram-negative bacterial cells for allowing photodynamic inactivation. The synthesis was achieved by the use of a common synthon of pentacationic N,N′,N,N,N,N-hexapropylhexa(aminoethyl)amine arm (C?N??) having six attached propyl groups, instead of methyl or ethyl groups, to provide a well-balanced hydrophobicity-hydrophilicity character to pentacationic precursor intermediates and better compatibility with the highly hydrophobic C?? cage moiety. We demonstrated two plausible synthetic routes for the preparation of 1 and 2 with the product characterization via various spectroscopic methods.     

Evaluation of an International Pharmacopoeia method for the analysis of nelfinavir mesilate by liquid chromatography

A gradient LC method for the determination of related substances in nelfinavir mesilate (NFVM) has been recently published in the International Pharmacopoeia. The method uses a base deactivated reversed phase C18 column (25 cm x 4.6 mm I.D.), 5 microm kept at a temperature of 35 degrees C. The mobile phases consist of acetonitrile, methanol, phosphate buffer pH 3.4 and water. The flow rate is 1.0 ml/min. UV detection is performed at 225 nm. A system suitability test (SST) is described to govern the quality of the separation. The separation towards NFVM components was investigated on 18 C18 columns and correlation was made with the column classification system developed in our laboratory. The method was evaluated using a Hypersil BDS C18 column (25 cm x 4.6 mm I.D.), 5 microm. A two level fractional factorial design was applied to examine the robustness of the method. The method shows good selectivity, precision, linearity and sensitivity. Seven commercial samples were examined using this method.     

Estimation of trace impurities in reactor-grade uranium using ICP-AES

Estimation of impurities in reactor grade uranium is important from the point of view of neutron economy. For chemical separation, ion exchange and solvent extraction techniques have been employed although the latter is generally preferred. Amongst various extractants TBP (tri-n-butyl phosphate), TBP-TOPO (tri-n-octyl phosphine oxide), or TOPO only (in CCl(4), xylene, dodecane) is most often used. New reagents like Cyanex-923 (mixture of 4 tri-alkyl phosphine oxides)/TEHP (tri-ethylhexyl phosphoric acid) are also being used. This communication reports chemical separation of uranium by precipitation using 1,2-diaminocyclohexane NNN'N'-tetra acetic acid (CyDTA)/ammonium hydroxide in presence of 1,10-phenanthroline and estimation of impurities in the filtrate by ICP-AES. Quantitative separation of U, a high spectral interferent in plasma and recovery of impurities have been achieved. Recovery of Cd has been improved by using 1,10-phenanthroline. The method is accurate and precise, offering a relative standard deviation ranging from less than 4% (3.8% for Eu at the 10mug g(-1) level) to 12.9% (for Ce at the 2.5 mug g(-1) level) for all the elements studied.     

First stereoselective total synthesis of helicascolides A and C

The first total synthesis of helicascolides A and C is reported via acid catalyzed acetonide deprotection followed by intramolecular lactonization in one-pot as the key step.     

Sequential one-pot method for oxy-Michael addition,Heck coupling,and degradation followed by condensation: facile synthesis of 2-benzoxepin-3(1H)-ones

A sequential one-pot intermolecular oxy-Michael addition, intermolecular Heck coupling, and intramolecular degradation (retro-oxy-Michael addition) followed by condensation method has been developed for the synthesis of interesting 2-benzoxepin-3(1H)-ones. Significantly, the 2-benzoxepin-3(1H)-ones form the core quantum of biologically vital natural products. The initial oxy-Michael addition and Heck coupling steps involve a straight forward construction of C–O and C–C bonds, whereas, the final condensation step follows a novel mechanistic path via intramolecular degradation, double bond isomerization, and intramolecular condensation. Notably, a remarkable solvent effect has been observed in-order to promote the final intramolecular condensation.