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.

     

An Enumerative Geometry for Magic and Magilatin Labellings

A magic labelling of a set system is a labelling of its points by distinct positive integers so that every set of the system has the same sum, the magic sum. Examples are magic squares (the sets are the rows, columns, and diagonals) and semimagic squares (the same, but without the diagonals). A magilatin labelling is like a magic labelling but the values need be distinct only within each set. We show that the number of n × n magic or magilatin labellings is a quasipolynomial function of the magic sum, and also of an upper bound on the entries in the square. Our results differ from previous ones because we require that the entries in the square all be different from each other, and because we derive our results not by ad hoc reasoning but from a general theory of counting lattice points in rational inside-out polytopes. We also generalize from set systems to rational linear forms. Dedicated to the memory of Claudia Zaslavsky, 1917–2006 Received August 10, 2005     

Nonaqueous diazotization of 4-amino-3-arylisothiazole-5-carboxylate esters

4-Amino-3-arylisothiazole-5-carboxylate esters are converted to the corresponding desamino, chloro, bromo, and iodo esters by processes involving nonaqueous diazotization. These related procedures open up the possibility for the conversion of readily available heterocyclic ortho-amino esters and nitriles to related heterocyclic derivatives, which are not easily obtained by alternate routes.     

The neutral weak current of the nucleon

A brief review of the structure of the nucleon as determined through parity-violating electron scattering is presented. The relationship between the electromagnetic and neutral weak currents is developed in a pedagogical introduction. Recent results and present measurements are discussed.     

Separation of non UV-absorbing cations by capillary electrophoresis

Summary A new buffer system for the separation of cations with capillary electrophoresis using indirect UV-detection is described. p-Aminopyridine can be used in the wide pH-range between 3 and 10. High-speed separations of positively charged non-UV absorbing ions are possible. Separation of ions with similar mobilities can be achieved by the addition of complexation reagents. The separation of potassium and ammonium is possible either with the addition of crown ether or at high pH-values. Transition metals can be separated by adding 2-hydroxybutyric acid to the buffer.Dedicated to Professor Dr. Wilhelm Fresenius on the occasion of his 80th birthday