Development and Validation of Stability Indicating RP-HPLC Method for the Determination of Process and Degradation-Related Impurities in Sugammadex Sodium Drug Substance

The aim of this study is to develop and validate a sensitive and specific stability-indicating reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the quantitative determination of Sugammadex sodium together with its process and possible degradation impurities. The pKa value is 2.82. The chromatographic conditions have been optimized by the Hypersil Gold 250 mm X 4.6 mm, 3 µ RP-18 columns with gradient elution using a mobile phase composed of 0.1% phosphoric acid, acetonitrile, and methanol. The eluents were monitored at 205 nm with a flow rate of 1.0 mL/min with an injection volume of 20 µL. The optimized method produced symmetrical and sharp peaks with good separation between the process and degradation impurities. The forced degradation study was carried out under acid, base, oxidation, and thermal conditions to demonstrate the stability-indicating capability of the method. The method was validated as per the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) and showed excellent specificity, precision, linearity, accuracy, and robustness. The developed HPLC method was precise with a value of 0.25%. The relative standard deviation of accuracy represented by the recovery studies ranged between 89.5% and 104.6%. Linearity analyses indicated a correlation coefficient value of greater than 0.996 for Sugammadex and its known impurities. The LOD and LOQ values for Sugammadex ranged from 0.017% to 0.050%, and for its related impurities, they ranged from 0.015% to 0.055%. The stability of the analytical solution was evaluated and was stable for 75 h when stored at 5 °C. No chromatographic interference was observed during the degradation studies and also in the blank chromatogram.

     

Light and heat control over secondary structure and amyloid-like fiber formation in an overcrowded-alkene-modified Trp zipper

The external photocontrol over peptide folding, by the incorporation of molecular photoswitches into their structure, provides a powerful tool to study biological processes. However, it is limited so far to switches that exhibit only a rather limited geometrical change upon photoisomerization and that show thermal instability of the photoisomer. Here we describe the use of an overcrowded alkene photoswitch to control a model β-hairpin peptide. This photoresponsive unit undergoes a large conformational change and has two thermally stable isomers which has major influence on the secondary structure and the aggregation of the peptide, permitting the phototriggered formation of amyloid-like fibrils.     

Invariant Dissipative Mechanisms for the Spatial Motion of Rods Suggested by Artificial Viscosity

The introduction of artificial viscosity into the partial differential equations of mechanics is often useful for both analytic and numerical studies. The traditional forms of artificial viscosity, originally designed to treat problems for fluids, when applied to problems for solids often lead to equations describing material properties that are not invariant under rigid motions. Consequently, for rapidly rotating bodies, artificial viscosity could produce serious errors. In this paper it is shown how to introduce artificial viscosity in a properly invariant way, and that the resulting systems have a rich and attractive structure, which beckons analysis.     

Generalizations of the Nikodym boundedness and Vitali–Hahn–Saks theorems

Generalizations of the Nikodym boundedness and Vitali–Hahn–Saks theorems for scalar-valued measures on rings of sets that are in general not σ-rings are presented. As a consequence, the rings of subsets of N with density zero and uniform density zero are shown to have the Nikodym property. In addition, vector measure generalizations of the Vitali–Hahn–Saks theorem are given.     

Investigation into the absolute stereochemistry of the marine sponge alkaloid pyrinodemin A

The absolute configuration of the marine sponge alkaloid pyrinodemin A is established by organic synthesis.     

Ambient connections realising conformal Tractor holonomy

For a conformal manifold we introduce the notion of an ambient connection, an affine connection on an ambient manifold of the conformal manifold, possibly with torsion, and with conditions relating it to the conformal structure. The purpose of this construction is to realise the normal conformal Tractor holonomy as affine holonomy of such a connection. We give an example of an ambient connection for which this is the case, and which is torsion free if we start the construction with a C-space, and in addition Ricci-flat if we start with an Einstein manifold. Thus, for a C-space this example leads to an ambient metric in the weaker sense of Čap and Gover, and for an Einstein space to a Ricci-flat ambient metric in the sense of Fefferman and Graham. Current address for first author: Erwin Schr?dinger International Institute for Mathematical Physics (ESI), Boltzmanngasse 9, 1090 Vienna, Austria Current address for second author: Department of Mathematics, University of Hamburg, Bundesstra?e 55, 20146 Hamburg, Germany