Comparison of Two Stability-Indicating Chromatographic Methods for the Determination of Mirabegron in Presence of Its Degradation Product

Mirabegron is a novel β₃-adrenoceptor agonist containing an amide group. It was subjected to stress conditions of acidic and alkaline hydrolyses. The hydrolytic degradation product was isolated and its structure was confirmed using mass and IR spectrometry. Two stability-indicating chromatographic methods have been proposed for the determination of mirabegron. TLC method was applied using silica gel as stationary phase and chloroform–methanol–ammonia (9.0:1.0:0.1 by volume) as the mobile phase, and chromatograms were scanned at 250 nm. Accurate determination of the drug was achieved over the concentration range of 2–12 μg per band. In addition, an isocratic HPLC method was developed on Agilent C18 column (150 mm × 4.5 mm I.D., particle size 5 µm) using ethanol-phosphate buffer pH 2.5 (30:70, by volume) as a mobile phase with flow rate of 1 mL min^?1.The intact drug was detected at 250 nm with running time less than 5 min. Mirabegron was determined accurately in a concentration range of 1–25 µg mL^?1. The proposed chromatographic methods were applied successfully for the assay of mirabegron in pharmaceutical dosage form and both methods were validated as per the International Conference on Harmonization guidelines and statistically compared with a reported gradient HPLC method.     

Studies on electron transfer reactions: reduction of heteropoly 10-tungstodivanadophosphate by <Emphasis Type="SmallCaps">l</Emphasis>-cysteine in aqueous acid medium

l-cysteine undergoes facile electron transfer with heteropoly 10-tungstodivanadophosphate, [ \textPV^\textV \textV^\textV \textW _{1 0} \textO _{4 0} ]^{5 -} , \left[ {{\text{PV}}^{\text{V}} {\text{V}}^{\text{V}} {\text{W}}_{ 1 0} {\text{O}}_{ 4 0} } \right]^{5 - } , at ambient temperature in aqueous acid medium. The stoichiometric ratio of [cysteine]/[oxidant] is 2.0. The products of the reaction are cystine and two electron-reduced heteropoly blue, [PV^IVV^IVW₁₀O₄₀]⁷⁻. The rates of the electron transfer reaction were measured spectrophotometrically in acetate–acetic acid buffers at 25 °C. The orders of the reaction with respect to both [cysteine] and [oxidant] are unity, and the reaction exhibits simple second-order kinetics at constant pH. The pH-rate profile indicates the participation of deprotonated cysteine in the reaction. The reaction proceeds through an outer-sphere mechanism. For the dianion ⁻SCH₂CH(NH₃ ⁺)COO⁻, the rate constant for the cross electron transfer reaction is 96 M⁻¹s⁻¹ at 25 °C. The self-exchange rate constant for the ^- \textSCH₂ \textCH( \textNH₃ ⁺ )\textCOO ^- \mathord

Evaluation of a Vancomycin-Based LC Column in Enantiomeric Separation of Atenolol: Method Development, Repeatability Study and Enantiomeric Impurity Determination

An LC method was developed and validated for the enantioselective separation and enantiomeric impurity quantitation of atenolol. Separation of the atenolol enantiomers on the Chirobiotic V2 (150 mm × 4.6 mm, 5 μm) column was best achieved using a ternary mobile phase of methanol–acetonitrile-triethylamine acetate 0.5% (w/v), pH 4.5 in a ratio of (45:50:5; v/v/v). Good resolution value of R _s  = 3 was obtained at a flow rate of 1 mL min^?1 within a total run time of less than 40 min. Peak identification was achieved using the standard reference of individual enantiomers. The peak of the impurity was eluted in front of the peak of the main enantiomer. Detection was performed by UV at 226 nm. Within and between day’s repeatabilities for both retention time and peak area were investigated at three concentration levels and found to be low. The method was also found to be efficient for the determination of atenolol enantiomeric impurity. An impurity quantitation level of (R)-atenolol down to 0.08% relative to the main enantiomer (S)-atenolol was found possible.     

Assessment of labelled products with different radioanalytical methods: study on 18F-fluorination reaction of 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF)

The serotonin receptor 5-HT_1A ligand 4-[¹⁸F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[¹⁸F]MPPF) was produced by a simplified method of Le Bars et al. Traditional oil bath heating was compared to microwave heating. Various radioanalytical methods, radio-Thin Layer Chromatography (TLC), High Pressure Liquid Chromatography (HPLC) and Mass Spectrometry (MS), were compared in the evaluation of the labelled product(s). The crude reaction mixture consisted of p-[¹⁸F]MPPF and 2–4 radioactive by-products eluting after the product fraction, and the reverse-phase HPLC method failed occasionally to separate p-[¹⁸F]MPPF from the radioactive by-product with close retention time. The heating method had no significant effect on the composition of labelled by-products. In LC-(ESI)-MS analysis of p-[¹⁸F]MPPF the labelled product was identified with m/z ratio of 435 ([M + H⁺]). The other HPLC fractions were measured to have following m/z ratios: (1) 327; 349; (675) (2) 402; 407/408; (791) and (3) 436, suggesting different kind of decomposition of the labelled product and/or the inactive precursor. The ion trap mass spectrometer was sufficient for the qualitative analysis of p-[¹⁸F]MPPF. However, differentiation of by-products arising from the decomposition of p-[¹⁸F]MPPF or from its precursor p-MPPNO₂ proved to be challenging.     

An unusual bioactive oleanane triterpenoid from Rhododendron campanulatum D.Don

An unusual oleanane triterpene(1) was isolated from aerial parts of Rhododendron campanulatum.The compound had shown prominent antibacterial and immunomodulatory activities.The structure of the compound was determined by spectroscopic data including 1D and 2D NMR spectral analysis.     

Synthesis of a C-2 Stapled Bis-Lexitropsin

Summary. A convenient synthesis method was developed for the preparation of C-stapled homodimeric bis-lexitropsins connected through the nitrogen atoms of the central pyrrole ring with a bis-methylene linker. This lexitropsin is designed as a standard for other bis-lexitropsins with longer chains in biological evaluation and NMR studies. The key step in this method is the treatment of ethyl 4-nitropyrrole-2-carboxylate with flame-dried potassium carbonate in DMF followed by the addition of 1,2-dibromoethane to form the 1,2-dipyrroloethane derivative.     

The Hamilton formalism with fractional derivatives

Recently the traditional calculus of variations has been extended to be applicable for systems containing fractional derivatives. In this paper the passage from the Lagrangian containing fractional derivatives to the Hamiltonian is achieved. The Hamilton's equations of motion are obtained in a similar manner to the usual mechanics. In addition, the classical fields with fractional derivatives are investigated using Hamiltonian formalism. Two discrete problems and one continuous are considered to demonstrate the application of the formalism, the results are obtained to be in exact agreement with Agrawal's formalism.     

Singular limits for a 4-dimensional semilinear elliptic problem with exponential nonlinearity

Using some nonlinear domain decomposition method, we prove the existence of branches of solutions having singular limits for some 4-dimensional semilinear elliptic problem with exponential nonlinearity.     

Triple collisions in the isosceles three body problem with small mass ratio

We use a slightly modified version of McGehee's transformation to study the triple collisions of the isosceles three body problem in a way that allows us to let the mass ratio go to zero. We study the limiting case and show that the collision manifold changes topologically, which affects the behaviour of near collision orbits. We also obtain new information about the flow on the collision manifold when the mass ratio is small.