Bulk Impurities Research Articles

Determination of Cetirizine and Its Impurities in Bulk and Tablet Formulation Using a Validated Capillary Zone Electrophoretic Method

Determination of Cetirizine and Its Impurities in Bulk and Tablet Formulation Using a Validated Capillary Zone Electrophoretic Method

APPLICATION OF SDS MICELLES AS CARRIERS FOR RELIABLE DETERMINATION OF FEXOFENADINE AND ITS IMPURITIES IN BULK AND PHARMACEUTICAL FORMULATIONS BY CAPILLARY MICELLAR ELECTROPHORESIS

A reversed-polarity capillary electrophoretic method based on application of sodium dodecyl sulfate (SDS) micelles as the carriers was developed for separation and determination of Fexofenadine (FXN) hydrochloride and its three major structural impurities in bulk and a tablet dosage form. CE analysis was performed using untreated fused-silica capillary of 50 µm internal diameter and 75-cm total length (25-cm effective length). The voltage applied of −25 kV at 25°C, and the detection wavelength was set at 225 nm. The running buffer was a 150 mM phosphate buffer at pH = 3.0, containing 22% v/v acetonitrile and 25 mmol SDS. Terfenadine was used as the internal standard (IS). The proposed method was found selective for determination of the main drug and its major impurities. The limit of quantification (LOQ) for FXN and impurities D10, D11, and A were found 70 µg/mL, 50 µg/mL, 80 µg/mL, and 100 µg/mL, respectively. The regression data obtained from the calibration plots indicated linear relationship (r2 = 0.997) over the concentration range of 70–500 µg/mL of FXN. Repeatability and reproducibility of the method, assessed as intra-day and inter-day variation and expressed as RSD (%), were less than 4% for relative peak area. Then, the method was applied for the determination of FXN in bulk and a tablet dosage form.

A Study of Transition‐Metal Organometallic Complexes Combining 35Cl Solid‐State NMR Spectroscopy and 35Cl NQR Spectroscopy and First‐Principles DFT Calculations

A series of transition-metal organometallic complexes with commonly occurring metal-chlorine bonding motifs were characterized using (35)Cl solid-state NMR (SSNMR) spectroscopy, (35)Cl nuclear quadrupole resonance (NQR) spectroscopy, and first-principles density functional theory (DFT) calculations of NMR interaction tensors. Static (35)Cl ultra-wideline NMR spectra were acquired in a piecewise manner at standard (9.4 T) and high (21.1 T) magnetic field strengths using the WURST-QCPMG pulse sequence. The (35)Cl electric field gradient (EFG) and chemical shielding (CS) tensor parameters were readily extracted from analytical simulations of the spectra; in particular, the quadrupolar parameters are shown to be very sensitive to structural differences, and can easily differentiate between chlorine atoms in bridging and terminal bonding environments. (35)Cl NQR spectra were acquired for many of the complexes, which aided in resolving structurally similar, yet crystallographically distinct and magnetically inequivalent chlorine sites, and with the interpretation and assignment of (35)Cl SSNMR spectra. (35)Cl EFG tensors obtained from first-principles DFT calculations are consistently in good agreement with experiment, highlighting the importance of using a combined approach of theoretical and experimental methods for structural characterization. Finally, a preliminary example of a (35)Cl SSNMR spectrum of a transition-metal species (TiCl4) diluted and supported on non-porous silica is presented. The combination of (35)Cl SSNMR and (35)Cl NQR spectroscopy and DFT calculations is shown to be a promising and simple methodology for the characterization of all manner of chlorine-containing transition-metal complexes, in pure, impure bulk and supported forms.

Development and validation of stability-indicating UPLC method for the determination of lafutidine and its impurities in bulk and pharmaceutical dosage form

Abstract Background A simple and rapid stability-indicating, reversed phase ultra-performance liquid chromatography (UPLC) method was developed for the quantitative determination of lafutidine and its four potential impurities. Results Separation was achieved on Acquity BEH-shield RP18 UPLC column (3.0 mm × 100 mm, 1.7 μm) under the gradient mode of elution by using mobile phase A (0.02M diammonium hydrogen phosphate/acetonitrile, 80:20 v/v) and mobile phase B (0.02M diammonium hydrogen phosphate/acetonitrile, 30:70 v/v). The flow rate was maintained at 0.5 mL min−1. UV detection was carried out at 276 nm. Conclusions Stability-indicating capability of the developed method is established by analyzing forced degradation samples in which the spectral purity of lafutidine is ascertained along with the separation of degradation products from analyte peak. The developed UPLC method is validated as per International Conference on Harmonization guidelines with respect to system suitability, specificity, precision, sensitivity, accuracy, linearity, and robustness.

Stability of Weyl metals under impurity scattering

We investigate the effects of bulk impurities on the electronic spectrum of Weyl semimetals, a recently identified class of Dirac-type materials. Using a $T$-matrix approach, we study resonant scattering due to a localized impurity in tight binding versions of the continuum models recently discussed by Burkov, Hook, and Balents, describing perturbed four-component Dirac fermions in the vicinity of a critical point. The impurity potential is described by a strength $g$ as well as a matrix structure $\Lambda$. Unlike the case in d-wave superconductors, where a zero energy resonance can always be induced by varying the impurity scalar and/or magnetic impurity strength, we find that for certain types of impurity ($\Lambda$), the Weyl node is protected, and that a scalar impurity will induce an intragap resonance over a wide range of scattering strength. A general framework is developed to address this question, as well as to determine the dependence of resonance energy on the impurity strength.

Comment on “Phase diagram of reentrant and magnetic-field-induced superconducting states with Kondo impurities in bulk and proximity-coupled compounds”

The Meissner effect induced in a normal metal in close contact with a superconductor is known to weaken at very low temperatures, and to be restored by the application of a moderate magnetic field [Visani et al., Phys. Rev. Lett. 65, 1514 (1990)]. This reentrant behavior was recently interpreted as resulting from the presence of Kondo impurities in the normal metal, with calculated concentrations on the order of 100 ppm [Simons et al., Phys. Rev. B 86, 064509 (2012)]. We show here that in fact the presence of magnetic impurities in the normal metal at such concentrations is ruled out by the absence of a minimum of resistivity in the same samples down to 2 K.

Reply to “Comment on ‘Phase diagram of reentrant and magnetic-field-induced superconducting states with Kondo impurities in bulk and proximity-coupled compounds’ ”

The existence of Kondo impurities has recently been suggested as an explanation for the long-standing puzzle of paramagnetic reentrance in thick proximity systems. We show here that despite recent claims to the contrary such impurities may still be the source of this effect.

Development and validation of a reversed phase liquid chromatographic method for analysis of griseofulvin and impurities

A simple and robust reversed phase liquid chromatographic method was developed and validated for the quantitative determination of griseofulvin (GF) and its impurities in drug substances and drug products (tablets). Chromatographic separation was achieved on a Discovery C18 (250mm×4.6mm, 5μm) column kept at 30°C. The mobile phase consisted of a gradient mixture of mobile phase A (water–0.1% formic acid pH 4.5, 80:20, v/v) and B (ACN–water–0.1% formic acid pH 4.5, 65:15:20, v/v/v) pumped at a flow rate of 1.0mL/min. UV detection was performed at 290nm. The method was validated for its robustness, sensitivity, precision, accuracy and linearity based on ICH guidelines. The robustness study was performed by means of an experimental design and multivariate analysis. Satisfactory results were obtained from the validation studies. The use of volatile mobile phases allowed for the identification of three main impurities present above the identification threshold using mass spectrometry (MS). The developed LC method has been applied for the assay and impurity determination of GF drug substances and tablets. The method could be very useful for the quality control of GF and its impurities in bulk and formulated dosage forms.

Helium impurity nanocluster gels in superfluid helium

Rapid cooling of a helium impurity gas mixture to the superfluid helium temperatures allows us to prepare an impurity-helium condensate with jelly-like structure (impurity gel) in superfluid He-II. It is clear that the properties of these gels should be substantially different from those of a bulk impurity substance, constituting a new class of soft matter — quantum gel, where superfluid He-II filling the nanopores between the randomly connected impurity nanoclusters serves as the dispersion medium of the gel.

Impurity and edge roughness scattering in graphene nanoribbons: the Boltzmann approach

The conductivity of graphene nanoribbons in the presence of bulk impurities and edge roughness is studied theoretically using the Boltzmann transport equation for quasi-one-dimensional systems. As the number of occupied subbands increases, the conductivity due to bulk impurities converges towards the two-dimensional case. It is shown that the dependence of the conductivity generated by edge roughness scattering depends in a distinctly different way on the sample parameters than the conductivity due to bulk scattering. The Boltzmann model furthermore predicts the amplitude of the edge-roughness-induced magnetoconductance dip as a function of the amplitude and the correlation length of the edge roughness.

Application of a Validated Stability‐Indicating LC Method for the Simultaneous Estimation of Tapentadol and Its Process‐Related Impurities in Bulk and Its Dosage Form

Described is a first reported, simple, rapid, selective, and isocratic stability‐indicating RP‐LC method for the quantitative determination of tapentadol and its related substances in bulk samples and pharmaceutical dosage forms in the presence of its two process‐related impurities. Chromatographic separation was achieved on the reversed phase, Enable column (C18 (5‐μm, 250 × 4.6 mm, i.d.)) at ambient temperature using a mobile phase consisting of 0.02 M potassium dihydrogen orthophosphate (adjusted to pH 6 with 1 M KOH) and acetonitrile (80 : 20, v/v). Flow rate was 1 mL/min and retention time was found to be 7.7 ± 0.05 min. Quantitation was achieved with UV detection at 215 nm based on peak area with linear calibration curves at concentration range 75–300 μg/mL. Forced degradation studies were performed, in accordance with ICH guidelines, using acidic, alkaline, oxidative, neutral, photolytic, and thermal conditions. The drug was found to be stable under all the conditions. The developed method was validated in terms of precision, robustness, recovery, and limits of detection and quantitation. Regression analysis shows an “r” value (correlation coefficient) of greater than 0.999 for tapentadol and two potential impurities.

Phase diagram of reentrant and magnetic-field-induced superconducting states with Kondo impurities in bulk and proximity-coupled compounds

Reentrant behavior is known to exist and magnetic-field-induced superconductivity has been predicted in superconductors with Kondo impurities. We present a simple framework for understanding these phenomena and generalize it to explain the long-standing puzzle of paramagnetic reentrance in thick proximity systems as being due to Kondo impurities.

Development and Validation of Stability-Indicating GC-FID Method for the Quantitation of Memantine Hydrochloride and Its Nonchromophoric Impurities in Bulk and Pharmaceutical Dosages

A stability-indicating method has been developed and validated for the quantitative determination of memantine hydrochloride and its nonchromophoric impurities in drug substance and drug product using gas chromatography coupled with flame ionization detector (GC-FID). The stability-indicating nature of the method has been proved by establishing peak purity and confirming the mass balance of all samples by subjecting them to stress conditions like hydrolysis, oxidation, photolysis, and thermal degradation studies. The chromatographic separation was performed on a fused silica capillary (HP-5, 30 meter, 0.32 mm and 0.25 μm film thickness) column. The method validation results indicate that the method has acceptable specificity, accuracy, linearity, precision, robustness, and high sensitivity with detection limits and quantitation limits ranging from 0.001% to 0.01% and 0.004% to 0.03%, respectively. The effectiveness of the technique was demonstrated by analysis of different bulk sample of Memantine hydrochloride. The proposed GC-FID method was also found to be specific and selective for the analysis of commercial formulation samples.

The use of optical microscopy to examine crystallite nucleation and growth in thermally annealed plasma enhanced chemical vapor deposition and hot wire chemical vapor deposition a-Si:H films

We report a simple method to investigate crystallite nucleation and growth in stepwise, thermally annealed plasma enhanced chemical vapor deposition and hot wire chemical vapor deposition a-Si:H films. By confining film thicknesses to the range 500–4000 Å, optical microscopy in the reflection mode can be used to readily detect crystallites in the thermally annealed a-Si:H lattice. Measurements of the crystallite density versus annealing time for identically prepared films of different thickness show that the crystallite nucleation rate is smaller for thinner films, suggesting that crystallite nucleation is homogeneous, in agreement with previous results. A comparison of film nucleation rates with those obtained by other methods on identically prepared films shows excellent agreement, thus establishing the validity of the current technique. The potential effect of impurity (oxygen) incorporation during the stepwise annealing in air is shown not to affect crystallite nucleation and growth, in that SIMS oxygen profiles for stepwise versus continuous annealing show not only similar impurity profiles but also similar bulk impurity densities.

Mapping Itinerant Electrons around Kondo Impurities

We investigate single Fe and Co atoms buried below a Cu(100) surface using low temperature scanning tunneling spectroscopy. By mapping the local density of states of the itinerant electrons at the surface, the Kondo resonance near the Fermi energy is analyzed. Probing bulk impurities in this well-defined scattering geometry allows separating the physics of the Kondo system and the measuring process. The line shape of the Kondo signature shows an oscillatory behavior as a function of depth of the impurity as well as a function of lateral distance. The oscillation period along the different directions reveals that the spectral function of the itinerant electrons is anisotropic.

Measurements of the deuterium ion toroidal rotation in the DIII-D tokamak and comparison to neoclassical theory

Bulk ion toroidal rotation plays a critical role in controlling microturbulence and MHD stability as well as yielding important insight into angular momentum transport and the investigation of intrinsic rotation. So far, our understanding of bulk plasma flow in hydrogenic plasmas has been inferred from impurity ion velocity measurements and neoclassical theoretical calculations. However, the validity of these inferences has not been tested rigorously through direct measurement of the main-ion rotation in deuterium plasmas, particularly in regions of the plasma with steep pressure gradients where very large differences can be expected between bulk ion and impurity rotation. New advances in the analysis of wavelength-resolved Dα emission on the DIII-D tokamak [J. L. Luxon et al., Fusion Sci. Technol. 48, 807 (2002)] have enabled accurate measurements of the main-ion (deuteron) temperature and toroidal rotation. The Dα emission spectrum is accurately fit using a model that incorporates thermal deuterium charge exchange, beam emission, and fast ion Dα (FIDA) emission spectra. Simultaneous spectral measurements of counter current injected and co current injected neutral beams permit a direct determination of the deuterium toroidal velocity. Time-dependent collisional radiative modeling of the photoemission process is in quantitative agreement with measured spectral characteristics. L-mode discharges with low beam ion densities and broad thermal pressure profiles exhibit deuteron temperature and toroidal rotation velocities similar to carbon. However, intrinsic rotation H-mode conditions and plasmas with internal transport barriers exhibit differences between core deuteron and carbon rotation which are inconsistent with the sign and magnitude of the neoclassical predictions.

Influence of Surface Segregation on Wetting of Sn-Ag-Cu (SAC) Series and Pb-Containing Solder Alloys

Wetting of Sn-Ag-Cu (SAC) series solder alloys to solid substrates is strongly influenced by surface segregation of low-level bulk impurities in the alloys. We report in situ and real-time Auger electron spectroscopy measurements of SAC alloy surface compositions as a function of temperature as the alloys are taken through the melting point. A dramatic increase in the amount of surface C (and frequently O) is observed with temperature, and in some cases the alloy surface is nearly 80 at.% C at the melting point. The C originates from low-level impurities incorporated during alloy synthesis and inhibits wetting because C acts as a blocking layer to reaction between the alloy and substrate. A similar phenomenon has been observed over a wide range of (SAC and non-SAC) alloys synthesized by a variety of techniques. That solder alloy surfaces at melting have a radically different composition from the bulk uncovers a key variable that helps to explain the wide variability in contact angles reported in previous studies of wetting and adhesion.

Decoupling single nanowire mobilities limited by surface scattering and bulk impurity scattering

We demonstrate the isolation of two free carrier scattering mechanisms as a function of radial band bending in InN nanowires via universal mobility analysis, where effective carrier mobility is measured as a function of effective electric field in a nanowire field-effect transistor. Our results show that Coulomb scattering limits effective mobility at most effective fields, while surface roughness scattering only limits mobility under very high internal electric fields. High-energy α particle irradiation is used to vary the ionized donor concentration, and the observed decrease in mobility and increase in donor concentration are compared to Hall effect results of high-quality InN thin films. Our results show that for nanowires with relatively high doping and large diameters, controlling Coulomb scattering from ionized dopants should be given precedence over surface engineering when seeking to maximize nanowire mobility.

Solar Cell Emitters Fabricated by Flash Lamp Millisecond Annealing

Phosphorus ion implantation was used for the emitter formation in monoand multicrystalline silicon solar cells. After ion implantation the silicon is strongly disordered or amorphous within the ion range. Therefore subsequent annealing is required to remove the implantation damage and activate the doping element. Flash-lamp annealing offers here an alternative route for the emitter formation at overall low thermal budget. During flash-lamp annealing, only the wafer surface is heated homogeneously to very high temperatures at ms time scales, resulting in annealing of the implantation damage and electrical activation of phosphorus. However, variation of the pulse time also allows to modify the degree of annealing of the bulk region to some extent as well, which can have an influence on the gettering behaviour of metallic bulk impurities. The μ-Raman spectroscopy showed that the silicon surface is amorphous after ion implantation. It could be demonstrated that flash-lamp annealing at 800 ◦C for 20 ms even without preheating is sufficient to recrystallize implanted silicon. The highest carrier concentration and efficiency as well as the lowest resistivity were obtained after annealing at 1200 ◦C for 20 ms both for monoand multicrystalline silicon wafers. Photoluminescence results point towards P-cluster formation at high annealing temperatures which affects metal impurity gettering within the emitter.

Strontium zirconate as silicon and aluminum scavenger in yttria stabilized zirconia

Here we report on strontium zirconate as a getter for silicon dioxide and aluminum oxide in yttria stabilized zirconia (YSZ) single crystals for cleaning purposes. YSZ single crystals were covered with strontium zirconate powder and heat treated at 1450 °C in water vapor. After treatment the YSZ single crystals showed homogeneously distributed ball-sectioned features (bumps) across the external surface of the crystal. The composition as quantified by energy-dispersive X-ray spectroscopy (EDS) showed a large enrichment of silicon and aluminum in the bumps. From cross-section analysis by transmission electron microscopy (TEM) the interface region between bump and YSZ single crystal bulk was examined. EDS showed a homogeneous distribution of silicon and aluminum through the cross section of a bump. The results suggest strontium zirconate as a good getter for silicon and aluminum from bulk materials at elevated temperatures and prove a route to remove trace bulk impurities in YSZ.