Isolation of oxidative degradation products of atorvastatin with supercritical fluid chromatography

The isolation of four oxidative degradation products of atorvastatin using preparative high‐performance liquid chromatography applying at least two chromatographic steps is known from the literature. In this paper it is shown that the same four impurities could be isolated from similarly prepared mixtures in only one step using supercritical fluid chromatography. The methods for separation were developed and optimized. The preparation of the mixtures was altered in such a way as to enhance the concentration of desired impurities. Appropriate solvents were applied for collection of separated impurities in order to prevent degradation. The structures of the isolated impurities were confirmed and their purity determined. The preparative supercritical fluid chromatography has proven to be superior to preparative HPLC regarding achieved purity of standards applying fewer chromatographic as well as isolation steps. Copyright © 2015 John Wiley & Sons, Ltd.     

Stability-indicating RP-HPLC method development and validation for determination of nine impurities in apixaban tablet dosage forms. Robustness study by quality by design approach

A quality by design (QbD) based high-resolution HPLC method is described for determination of impurities in apixaban (APX) in the tablet dosage form. Employing a simple and stability-indicating HPLC method, nine known impurities were quantified with good peak resolution. Mobile phase A (MP-A) was prepared with buffer and acetonitrile 90:10 v/v, while mobile phase B (MP-B) contained water and acetonitrile 10:90 v/v. The gradient program was 0 min, MP-A 75%, B 25%; 20 min, MP-A 65%, B 35%; 30 min, MP-A 40%, B 60%; 40min, MP-A 40%, B 60%; 42 min, MP-A 75%, B 25%; and 50 min, MP-A 75%, B 25%. The chromatographic separation was achieved using a Zorbax RX C₁₈ 250 × 4.6 mm column, 5 μm (1.0 ml min⁻¹, 280 nm, 50 μl) and a column temperature of 40°C. Several separation studies were carried out using design of experiments to optimize the method. Validation results confirm the applicability of the developed method for quality analysis and stability studies of the regular product on the manufacturing stream.     

Stability indicating method for famotidine in pharmaceuticals using porous graphitic carbon column

A simple, sensitive and rapid HPLC method was developed and validated for the simultaneous determination of famotidine (FMT) and related impurities in pharmaceuticals. Chromatographic separation was accomplished within 10 min on a porous graphitic carbon (PGC) column using 50:50 v/v ACN-water containing 0.5% pentane sulphonic acid (PSA) as the mobile phase. Separation was achieved with a flow rate of 1 mL/min and a detection wavelength of 265 nm. The calibration curves were linear over a concentration range of 1.5-100 microg/mL. The intra- and interday RSDs (n = 5) for the retention times and peak area were all less than 2%. The method was sensitive with an LOD (S/N = 3) of 0.1 microg/mL for FMT, imp. C and 0.05 microg/mL for imp. 2, A and D. All recoveries were greater than 98%. The method was demonstrated to be precise, accurate and specific with no interference from the tablet ingredients and separation of the drug peak from the peaks of the degradation products (oxidative degradation and acid and base degradation). The results indicated that the proposed method could be used for the determination of FMT in commercial dosage forms and as a stability-indicating assay.     

Oscillatory zoning caused by oscillating surface relaxations

Oscillatory zoning is a spatial variation in the composition of minerals. It has been observed in many different minerals and a variety of mechanisms have been proposed to explain it. We propose an equilibrium model of oscillatory zoning in which the variations in composition stabilise a ferroelastic phase. This results in a sinusoidal variation in composition. We expect that this mechanism could account for oscillatory zoning found in minerals with oscillatory surface relaxations. Received 9 March 1999     

On dewetting dynamics of solid films of hydrogen isotopes and its influence on tritium ß spectroscopy

The dewetting dynamics of solid films of hydrogen isotopes, quench-condensed on a graphite substrate, was measured at various temperatures below desorption by observing the stray light from the film. A schematic model describing the dewetting process by surface diffusion is presented, which agrees qualitatively with our data. The activation energies of different hydrogen isotopes for surface diffusion were determined. The time constant for dewetting of a quench-condensed film at the working temperature of 1.86 K of the mainz neutrino mass experiment was extrapolated. Received 30 December 1999     

Cooperativity in a spin transition ferrous polymer: Interacting domain model, thermodynamic, optical and EPR study

A new thermodynamic model is proposed in order to account for the high spin low spin conversion in metal-organic polymers. The model, based on the idea that the spin conversion occurs in interacting domains of like-spin metal ions, allows to explain most of the important features of various types of spin conversion. The sine qua non condition of the existence of spin transitions with hysteresis is obtained. In the case of very large cooperativity, the model predicts unusual behaviour of the spin conversion system due to a low-temperature metastable high spin state. Existence of such a state is interesting in the context of the light induced excited spin state trapping recently observed in some ferrous compounds. The model is applied to interpret the spin transition in polycrystalline ferrous polymer [Fe _1-y Cu _y (Htrz)₂ trz] (BF ₄) with y = 0.00, 0.01 and 0.10, detected by differential scanning calorimetry, optical reflectivity and electron paramagnetic resonance. The domain size and the interaction energy between the domains are estimated as, respectively, n = 11 and for the y = 0 compound. As the copper content is growing, n and tend to decrease, resulting in transformations of the shape of hysteresis loop which becomes less steep, narrows and shifts to lower temperatures. The electron paramagnetic resonance gives further evidence of the presence of like-spin domains. Received 27 November 1998 and Received in final form 19 April 1999     

钢中小角度晶界区的电子结构及掺杂效应

根据位错的弹性理论,建立了9Ni钢中53°掺杂小角度晶界的原子模型,利用Recursion方法,计算了杂质在53°小角度晶界典型环境中的能量和电子结构,由此得出,钢中小角度晶界的强度敏感地依赖于隔离杂质的类型,S,P杂质使晶粒间结合减弱,从而导致晶界疏松 ;相反,B,C,N则会使晶界间的结合加强.在所有的杂质中,B显示出独特的性质,在钢中B 不仅能增强晶界的结合,而且由于占位竞争效应会使其他杂质远离晶界,具有净化晶界的作用. 关键词： 小角晶界 杂质 占位竞争 晶界隔离     

Semiempirical calculations on WO3 and MXWO3 crystals (M = H,Li, Na)

The monoclinic structure of tungsten trioxide WO₃ has been studied by combining a modified intermediate neglect of differential overlap (INDO) method and the supercell model. The fitted semiempirical parameters describe very well the features of the band structure and crystal structure. Calculations of H, Li, and Na impurities in a WO₃ crystal have been performed to study the absorption spectra and the equilibrium geometries of intercalated impurities. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 63: 729–735, 1997     

Binding energy of hydrogenic impurity states in an inverse parabolic quantum well under static external fields

In the present theoretical study, we investigate the influence of external fields (electric and/or magnetic) on the binding energy of hydrogenic impurities in a GaAs/Ga_1-xAl_xAs inverse parabolic quantum well, in which the parabolicity depends on the Al concentrations at the well center. Our calculations have been based on the potential morphing method in the effective mass approximation. The systematic theoretical investigation contains results with all possible combinations of the involved parameters, as quantum well width, Al concentrations at the well center, position of the impurity and magnitudes of the external fields.     

Sample stacking for determination of aromatic acid impurities by microemulsion electrokinetic chromatography

In this study, a sample stacking step coupled with microemulsion electrokinetic chromatography (MEEKC) was used to detect and analyze nine aromatic acids (benzoic acid (BA), isophthalic acid (IPA), terephthalic acid (TPA), p-toluic acid (p-TA), 4-carboxylbenzaldehyde (4-CBA), trimesic acid (TSA), trimellitic acid (TMA), o-phthalic acid (OPA), and hemimellitic acid (HMA)) which are common impurities produced during aromatic acid synthesis. First, the presence of both acid and water plugs at the front of the capillary improved the reproducibility in retention time and peak intensity of the tested analytes in the stacking method. Second, the pH and the electrolyte type of acidic plug and sample matrix were found to be the predominant influences on the aromatic acid stacking. The detection limits of these aromatic acids were reduced to the range of 0.00007-0.00032 μg mL⁻¹ by this optimal sample stacking step. This proposed on-line concentration MEEKC method was able to detect trace levels of aromatic acid impurities in commercial aromatic acid products that were not previously possible by the normal MEEKC method. Furthermore, these results in comparison with our previous studies on sample stacking MEEKC method indicated that all acidic species were concentrated by this simple stacking procedure. The sensitivity enhancement, however, was highly dependent on the types of functional groups present in the structures of analytes, and the enhancement was in the order of first the compounds carrying both carboxy and hydroxy groups (e.g. phenolic acid), followed by carboxylic acid compounds (e.g. aromatic acid), and then phenol compounds (e.g. polyphenol).