Identification,control strategies,and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: A comprehensive review

Potential genotoxic impurities in pharmaceuticals at trace levels are of increasing concern to both pharmaceutical industries and regulatory agencies due to their possibility for human carcinogenesis. Molecular functional groups that render starting materials and synthetic intermediates as reactive building blocks for small molecules may also be responsible for their genotoxicity. Determination of these genotoxic impurities at trace levels requires highly sensitive and selective analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical research and development. Experimental guidance for the analytical determination of some important classes of genotoxic impurities is still unavailable in the literature. Therefore, the present review explores the structural alerts of commonly encountered potential genotoxic impurities, draft guidance of various regulatory authorities in order to control the level of impurities in drug substances and to assess their toxicity. This review also describes the analytical considerations for the determination of potential genotoxic impurities at trace levels and finally few case studies are also discussed for the determination of some important classes of potential genotoxic impurities. It is the authors’ intention to provide a complete strategy that helps analytical scientists for the analysis of such potential genotoxic impurities in pharmaceuticals.     

AC-Conductivity and proton transport number of BaZr0.90Al0.10O3-δ

AC-conductivity measurements of BaZr_0.90Al_0.10O_3−δ (where δ describes the number of oxygen ion vacancies per unit cell) in wet and dry N₂ have been carried out over the temperature range from 400 to 900 °C. Both atmospheres showed the usual Arrhenius behavior of BaZr_0.90Al_0.10O_2.95. The proton transport number,t _H, was also determined from the conductivity measurements of BaZr_0.90Al_0.10O_2.95 in wet and dry N₂ and takes up values of 0.97 and 0.78 in the temperature range 400 – 900 °C, respectively.     

Solid state photoelectrochemical cells utilising graphite thin films counter electrode

This paper reports the use of graphite thin films as a counter electrode of a solid state photoelectrochemical cells of ITO/TiO₂/PVC-LiClO₄/graphite. The photoelectrochemical cells material was a screen-printed layer of titanium dioxide onto an ITO-covered glass substrate which was used as a working electrode of the device. The solid electrolyte used was PVC-LiClO₄ that was prepared by solution casting technique. The graphite films which serve as a counter electrode were prepared onto glass substrate by electron beam evaporation technique at substrate temperatures variation of 25, 50, 100, 150 and 200 °C. The dependence of sheet resistance and surface morphology of the graphite films on substrate temperature were studied. The films deposited at 25 °C shows the smoothest surface morphology and the smallest grain size. Bigger grain size, rougher surface morphology of graphite film counter electrode. The current-voltage characteristics of four devices utilising the graphite counter electrode with different substrate temperature in dark as well as under illumination of 100 mWcm⁻² light from a tungsten halogen lamp were recorded at room temperature and at 50 °C, respectively. It was found that the photovoltaic parameters of the device such as short-circuit current density, J_sc and open-circuit voltage, V_oc increases with the decreasing average grain size of the graphite counter electrode. The device whose graphite film counter electrode was deposited onto the glass substrate at 25 °C gave the highest J_sc of 0.32 μA/cm² and V_oc of 117 mV, respectively.     

A comparison of the binding of metal complexes to duplex and quadruplex DNA

Electrospray ionisation mass spectrometry (ESI-MS) and circular dichroism (CD) spectroscopy were used to compare the binding of mononuclear nickel, ruthenium and platinum complexes to double stranded DNA (dsDNA) and quadruplex DNA (qDNA). CD studies provided evidence for the binding of intact complexes of all three metal ions to qDNA. ESI mass spectra of solutions containing platinum or ruthenium complexes and qDNA showed evidence for the formation of non-covalent complexes consisting of intact metal molecules bound to DNA. However, the corresponding spectra of solutions containing nickel complexes principally contained ions consisting of fragments of the initial nickel molecule bound to qDNA. In contrast ESI mass spectra of solutions containing nickel, ruthenium or platinum complexes and dsDNA only showed the presence of ions attributable to intact metal molecules bound to DNA. The fragmentation observed in mass spectral studies of solutions containing nickel complexes and qDNA is attributable to the lower thermodynamic stability of the former metal complexes relative to those containing platinum or ruthenium, as well as the slightly harsher instrumental conditions required to obtain spectra of qDNA. This conclusion is supported by the results of tandem mass spectral studies, which showed that ions consisting of intact nickel complexes bound to qDNA readily undergo fragmentation by loss of one of the ligands initially bound to the metal. The ESI-MS results also demonstrate that the binding affinity of each of the platinum and ruthenium complexes towards qDNA is significantly less than that towards dsDNA.     

Studies on coordination chemistry of a nitrogen–sulfur donor ligand with lighter and heavier metal ions and biological activities of its complexes

Complexes of S-benzyldithiocarbazate (SBDTC) with lighter and heavier metals, viz., Cr^III, Fe^III, Sb^III, Zr^IV, Th^IV and U^VI have been prepared and characterized by elemental analyses, conductivity measurements, and spectral studies. The complexes: [Cr(SBDTCA)₃],^** [Fe(SBDTCA)₃], [Sb(SBDTCA)₃], [Sb(SBDTCA)₂Cl · H₂O], [Zr(O)(SBDTCA)₂ · H₂O], [Th(SBDTCA)(NO₃)₃ · H₂O)], and [U(O)₂(SBDTCA)₂] were all prepared in alkaline media. They were all hexa-coordinated with bidentate, uninegative chelation of the ligand. [Fe(SBDTCA)₃], [Sb(SBDTCA)₃] and [Sb(SBDTCA)₂Cl · H₂O] were strongly effective against bacteria giving clear inhibition zones with Pseudomonas aeruginosa and Bacillus cereus. The compounds showed poor antifungal activity. The antimony complexes were strongly cytotoxic against leukemic cells with CD₅₀ values of 3.2–6.7 g cm^–3 as compared to the CD₅₀ value of 14.5 g cm^–3 of the free SbCl₃ molecule.     

Cerium oxide nanoparticles scavenge nitric oxide radical (˙NO)

In this study we have obtained evidence that cerium oxide nanoparticles (CeO(2) NPs) are able to scavenge nitric oxide radical. Surprisingly, this activity is present in CeO(2) NPs with a lower level of cerium in the 3+ state (CeO(2) NPs with low 3+/4+ ratio and therefore a reduced number of oxygen vacancies), in contrast to the superoxide scavenging properties which are correlated with an increased level of cerium in the 3+ state (CeO(2) NPs with high 3+/4+ ratio and therefore an increased number of oxygen vacancies).     

Effect of concentration and particle size on nonlinearity of Au nano-fluid prepared by γ (Co) radiation

Nonlinear properties of Au nano-fluid prepared by γ-radiation method at different concentrations were investigated. Measurements of nonlinear refractive index and nonlinear absorption coefficient were carried out using a single beam Z-scan technique. A green CW laser beam operated at 532 nm was used as excitation source. The Au nano-fluid shows a good third order nonlinear response. The sign of the nonlinear refractive index is found to be negative and the magnitude is in the order of 10⁻⁷ cm²/W. This nonlinear effect increases as the concentration increases from 3.119 × 10⁻⁴ to 2.354 × 10⁻³ M which correspond to particle sizes of 4.0-30.5 nm, respectively. A good linear relationship was obtained between nonlinear refractive index and concentration. However the relationship between nonlinear refractive index and particle size was nonlinear behavior.     

Surface plasmon resonance detection of copper corrosion in biodiesel using polypyrrole-chitosan layer sensor

Copper corrosion is one of the important parameters used for evaluating the quality of biodiesel. In this work, a polypyrrole-chitosan sensing layer was utilized for the detection of Cu²⁺ in biodiesel using the surface plasmon resonance technique. With the sensitivity of this sensor being about 0.1 ppm, different corrosion levels could be recognized in samples that were classified as class 1a according to the standard copper strip test.