Robust UHPLC Separation Method Development for Multi-API Product Containing Amlodipine and Bisoprolol: The Impact of Column Selection

This paper describes a new and fast ultra-high pressure liquid chromatographic separation of amlodipine and bisoprolol and all their closely related compounds, for impurity profiling purposes. Computer-assisted method development was applied and the impact of several state-of-the-art stationary phase column chemistries (50 × 2.1 mm, sub-2 μm, and core–shell type materials) on the achievable selectivity and resolution was investigated. The work was performed according to quality by design principles using design of experiment with three experimental factors; namely the gradient time (t _G), temperature (T), and mobile phase pH. Thanks to modeling software, it was proved that the separation of all compounds was feasible on numerous column chemistries within <10 min, by proper adjustments of variables. It was also demonstrated that the reliability of predictions was good, as the predicted retention times and resolutions were in good agreement with the experimental ones. The final, optimized method separates 16 peaks related to amlodipine and bisoprolol within 7 min, ensuring baseline resolution between all peak-pairs.     

Lanthanide dota-like complexes containing a picolinate pendant: structural entry for the design of Ln(III)-based luminescent probes

In this contribution we present two ligands based on a do3a platform containing a picolinate group attached to the fourth nitrogen atom of the cyclen unit, which are designed for stable lanthanide complexation in aqueous solutions. Potentiometric measurements reveal that the thermodynamic stability of the complexes is very high (log K = 21.2-23.5), being comparable to that of the dota analogues. Luminescence lifetime measurements performed on solutions of the Eu(III) and Tb(III) complexes indicate that the complexes are nine coordinate with no inner-sphere water molecules. A combination of density functional theory (DFT) calculations and NMR measurements shows that for the complexes of the heaviest lanthanides there is a major isomer in solution consisting of the enantiomeric pair Λ(δδδδ) and Δ(λλλλ), which provides square antiprismatic coordination (SAP) around the metal ion. Analysis of the Yb(III)-induced paramagnetic shifts unambiguously confirms that these complexes have SAP coordination in aqueous solution. For the light lanthanide ions however both the SAP and twisted-square antiprismatic (TSAP) isomers are present in solution. Inversion of the cyclen ring appears to be the rate-determining step for the Λ(δδδδ) ? Δ(λλλλ) enantiomerization process observed in the Lu(III) complexes. The energy barriers obtained from NMR measurements for this dynamic process are in excellent agreement with those predicted by DFT calculations. The energy barriers calculated for the arm-rotation process are considerably lower than those obtained for the ring-inversion path. Kinetic studies show that replacement of an acetate arm of dota by a picolinate pendant results in a 3-fold increase in the formation rate of the corresponding Eu(III) complexes and a significant increase of the rates of acid-catalyzed dissociation of the complexes. However, these rates are 1-2 orders of magnitude lower than those of do3a analogues, which shows that the complexes reported herein are remarkably inert with respect to metal ion dissociation.     

Thermal study on electrospun polyvinylpyrrolidone/ammonium metatungstate nanofibers: optimising the annealing conditions for obtaining WO<Subscript>3</Subscript> nanofibers

This article demonstrates how important it is to find the optimal heating conditions when electrospun organic/inorganic composite fibers are annealed to get ceramic nanofibers in appropriate quality (crystal structure, composition, and morphology) and to avoid their disintegration. Polyvinylpyrrolidone [PVP, (C₆H₉NO) _n ] and ammonium metatungstate [AMT, (NH₄)₆[H₂W₁₂O₄₀]·nH₂O] nanofibers were prepared by electrospinning aqueous solutions of PVP and AMT. The as-spun fibers and their annealing were characterized by TG/DTA-MS, XRD, SEM, Raman, and FTIR measurements. The 400–600 nm thick and tens of micrometer long PVP/AMT fibers decomposed thermally in air in four steps, and pure monoclinic WO₃ nanofibers formed between 500 and 600 °C. When a too high heating rate and heating temperature (10 °C min⁻¹, 600 °C) were used, the WO₃ nanofibers completely disintegrated. At lower heating rate but too high temperature (1 °C min⁻¹, 600 °C), the fibers broke into rods. If the heating rate was adequate, but the annealing temperature was too low (1 °C min⁻¹, 500 °C), the nanofiber morphology was excellent, but the sample was less crystalline. When the optimal heating rate and temperature (1 °C min⁻¹, 550 °C) were applied, WO₃ nanofibers with excellent morphology (250 nm thick and tens of micrometer long nanofibers, which consisted of 20–80 nm particles) and crystallinity (monoclinic WO₃) were obtained. The FTIR and Raman measurements confirmed that with these heating parameters the organic matter was effectively removed from the nanofibers and monoclinic WO₃ was present in a highly crystalline and ordered form.     

Analysis of the essential oil of Amsonia illustris

The root and leaf essential oils, present in trace amounts in Amsonia illustris Woods. (Apocynaceae), were isolated by steam distillation and their chemical constituents identified by GC-FID and GC-MS. More than 80% of the thirty volatile compounds in the leaf oil were identified, the major constituents being mainly sesquiterpenes like a-humulene (14.5%), beta-caryophyllene (12.4%) and guaiol (11.6%). The volatile ingredients of the root oil were pinocampheol, methyl salicylate, (2E,4E)- decadienal, eugenol and trans-isoeugenol.     

The structure of sets with few sums along a graph

We present common generalizations of some structure results of Freiman, Ruzsa, Balog-Szemerédi and Laczkovich-Ruzsa. We also give some applications to Combinatorial Geometry and Algebra, some of which generalize the aforementioned structure results even further.     

Reflecting a triangle in the plane

We prove that if the three angles of a triangleT in the plane are different from (60°, 60°, 60°), (30°, 30°, 120°), (45°,45°,90°),(30°,60°,90°), then the set of vertices of those triangles which are obtained fromT by repeating ‘edge-reflection’ is everywhere dense in the plane.     

X-ray photoelectron spectroscopy studies on solid xanthates

Two commonly used xanthates, potassium ethyl xanthate (KEX) and sodium isopropyl xanthate (NaiPX) were characterized by comparing their bulk and surface composition. The XPS spectra were recorded using Al K and Mg K excitation and potential sources of contamination were accounted for. Sulfate and carbonate contaminations were identified, both in the bulk and on the surface of the KEX sample. NaiPX contained hydroxyl- and carbonyl-type contaminations. The earlier published XPS spectral data on xanthates were compiled and compared with the results of this work.     

Thermal stability and crystal structure of bis(1,2 ethanediol)zinc sulfate

Single crystals of the complex bis(1,2-enthanediol)zinc sulfate have been prepared. The crystal structure was determined by X-ray crystallography. Both 1,2-ethanediol (ethylene glycol) molecules chelate the zinc ion, the four glycolic oxygen atoms and the two oxygen atoms of the sulfate ion forming an octahedron around the zinc. Each sulfate ion is bonded to two zincs, forming an endless polymer chain. A hydrogen-bonding network between the ethylene glycol molecules and the sulfate ions is observed. On heating, the complex melts and decomposes, a polymeric structure of the thermal intermediate product is suggested.     

A just basis

An old problem of P. Erdös and P. Turán asks whether there is a basisA of order 2 for which the number of representationsn=a+a′, a,a′∈A is bounded. Erd?s conjectured that such a basis does not exist. We answer a related finite problem and find a basis for which the number of representations is bounded in the square mean. Writing σ (n)=|{(a, a ^t ) ∈A ²:a+a′=n}| we prove that there exists a setA of nonnegative integers that forms a basis of order 2 (that is,s(n)≥1 for alln), and satisfies ∑_{n ? N} σ(N)² = O(N).     

Bis(dibenzo[c.e][1,2]oxaphosphorino)dichloroplatinum Complexes

Reaction of a series of P-amino and P-cycloalkoxy dibenzo[c.e][1,2]oxaphosphorines (1), (3) and (5) with cis-bis(benzonitrile)dichloroplatinum(II) afforded the title bis(dibenzooxaphosphorino) complexes (2), (4) and (6), respectively. In the case of chiral P-substituents, the complexes (4) and (6) were obtained in homo and heterochiral forms. Stereospecific ¹J(¹⁹⁵Pt–P) couplings found in the ³¹P-n.m.r. spectra of the products (2), (4) and (6) suggested the cis orientation of the identical substituents.