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 Therefore, the present review explores the structural alerts of commonly encountered potential genotoxic impurities, draft guidance of various regulatory authorities in order to control the level of impurities in drug substances and to assess their toxicity.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.     

Synthesis,Spectroscopy, Semi‐empirical and Biological Activities of Organotin(IV) Complexes with o‐Isopropyl Carbonodithioic Acid

New organotin(IV) complexes have been synthesized by treating potassium o‐isopropyl carbonodithioate with R₂SnCl₂/R₃SnCl in 1 : 2/1 : 1 M/L ratio. All complexes have been characterized by IR and NMR (¹H, ¹³C) spectroscopy. IR results shows that ligand acts as bidentate which is also confirmed by semi‐empirical study. NMR data reveals four coordinated geometry in solution. Computed positive heat of formation shows that complex 5 is thermodynamically unstable. UV/visible spectroscopy was used to assess the mode of interaction and binding of the complexes with DNA which shows that complex 5 exhibits higher binding constant as compared to complex 3 . In protein kinase inhibition assay, compound 3 was found most active, while other biological activities shows that triorganotin(IV) complexes are biologically more active as compared to diorganotin(IV) complexes.     

Biological evaluations and spectroscopic characterizations of 3-(4-ethoxyphenyl)-2-methylacrylate based organotin(IV) carboxylates derivatives

Six new organotin(IV) carboxylates, [Me₂SnL₂] (1), [n-Bu₂SnL₂] (2), [n-Oct₂SnL₂] (3), [Me₃SnL] (4), [n-Bu₃SnL] (5) and [Ph₃SnL] (6), where L = 3-(4-ethoxyphenyl)-2-methylacrylate, have been synthesized and characterized by FT-IR, NMR spectroscopy and elemental analyses. The synthesized compounds were tested for in vitro antibacterial and antifungal activities. The complexes 4–6 demonstrated higher activity than the complexes 1–3. UV-Vis absorption spectroscopy indicated that the ligand and its complexes interacted with DNA via partial intercalation as well as minor groove binding.

     

Homobimetallic organotin(IV) complexes with succinohydrazide Schiff base: Synthesis,spectroscopic characterization,and biological screening

Russian Journal of General Chemistry - Six new bis-diorganotin(IV) complexes, [(Me2Sn)2L] (1), [(Et2Sn)2L] (2), [(n-Bu2Sn)2L] (3), [(Ph2Sn)2L] (4), [(n-Oct2Sn)2L] (5), and [(tert-C4H9)2Sn)2L] (6),...     

Local commensurability graphs of solvable groups

The commensurability index between two subgroups A,B of a group G is [A:A∩B][B:A∩B]. This gives a notion of distance among finite index subgroups of G, which is encoded in the p-local commensurability graphs of G. We show that for any metabelian group, any component of the p-local commensurabilty graph of G has diameter bounded above by 4. However, no universal upper bound on diameters of components exists for the class of finite solvable groups. In the appendix we give a complete classification of components for upper triangular matrix groups in GL(2,𝔽_q).     

Additive preservers of Drazin invertible operators with bounded index

Let B(X) be the algebra of all bounded linear operators on an infinite-dimensional complex or real Banach space X. Given an integer n ≥ 1, we show that an additive surjective map Φ on B(X)preserves Drazin invertible operators of index non-greater than n in both directions if and only if Φ is either of the form Φ(T) = αATA~(-1) or of the form Φ(T) = αBT~*B~(-1) where α is a non-zero scalar,A:X → X and B:X~*→ X are two bounded invertible linear or conjugate linear operators.     

On commutativity of near-rings with generalized derivations

In this paper we prove some theorems of commutativity for near-rings with generalized derivations. As a consequence of the results obtained, we generalize some published results. Also, we give some examples to show that some conditions in some results obtained are not redundant.     

Rheological studies of the gelation of aqueous solutions of acrylamide-acrylic acid copolymers in the presence of chromium chloride

The gelation kinetics of aqueous solutions of acrylamideacrylic acid copolymers in the presence of chromium ions was studied with different rheometers. The gel time is found to vary with the principle of the apparatus because of a low shear dependence of the elongation of the macromolecules. The variations of the gel time with the experimental conditions of the gel preparation were investigated and we conclude that the gelation is governed by the oligornerization kinetics of the chromium ions which are instantaneously, complexated by the carboxylate groups of the polymer. The variation laws of the gel time and of the elastic modulus with chromium and polymer concentrations, temperature and ionic strength are in qualitative agreement with the structure of the temporary network of the semi-dilute solutions of these copolymers.     

On the interaction between the input signal and the singularity expansion method

For transient excitation, it is well known that the Singularity Expansion Method (SEM) is a late time technique that is not in general suitable for early time. Lossy dielectric slab studies, with bounded integrable finite-duration input signal, have shown that the SEM representation for early time requires an additional branch cut contribution and a modification of the SEM series for completeness. Other researchers indicated that the SEM representation is not complete for most cases of practical interest and that it may not converge for early time. In this paper, we present an approach, using the input signal, to obtain a convergent SEM series that is valid for early as well as for late time. In this approach the branch cut contribution is not needed and instead we have pole contributions form the input signal and a modified SEM series. In addition, two forms of SEM representations will be presented, the traditional form and the time varying coupling coefficient form. Furthermore, the interaction and the effect of the input signal choice on the SEM representation will be clarified. This will be done for a dielectric slab backed by a perfect conductor.