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.

     

A quasiconformal dynamic property of the disk

It is known that every conformai embedding of the disk into the extended complex plane possesses a r²-quasiconformal extension across eachr-level line (the r²-property of a domain). We show here that this is a characteristic property of the disk: any simply connected domain which is not a disk does not admit ther ²-property. Supported by the RiP-program of the Volkswagen-Stiftung in the Mathematisches Forschungsinstitut Oberwolfach.     

Magnetism in disordered magnetic Fe82−xNixCr18

The zero field μSR-method has been used to study the magnetism in the disordered magnetic alloy Fe_82−xNi_xCr₁₈ near the three-critical, pointx=25. The dynamic and static local field distributions are analyzed. The difference between spin-glass states obtained either from the paramagnetic or after the double transition is discussed.     

Skew Models II

If g and G are the pdf and the cdf of a distribution symmetric around 0 then the pdf 2g(u)G(λ u) is said to define a skew distribution. In this paper, we provide a mathematical treatment of the skew distributions when g and G are taken to come from one of Pearson type II, Pearson type VII or the generalized t distribution.      

On then-cutset property

For a partially ordered setP and an elementx ofP, a subsetS ofP is called a cutset forx inP if every element ofS is noncomparable tox and every maximal chain ofP meets {x}∪S. We letc(P) denote the smallest integerk such that every elementx ofP has a cutsetS with ‖S‖?k: Ifc(P)?n we say thatP has then-cutset property. Our results bear on the following question: givenP, what is the smallestn such thatP can be embedded in a partially ordered set having then-cutset property? As usual, 2 ⁿ denotes the Boolean lattice of all subsets of ann-element set, andB _n denotes the set of atoms and co-atoms of 2 ⁿ . We establish the following results: (i) a characterization, by means of forbidden configurations, of whichP can be embedded in a partially ordered set having the 1-cutset property; (ii) ifP contains a copy of 2 ⁿ , thenc(P)?2^[n/2]?1; (iii) for everyn>3 there is a partially ordered setP containing 2 ⁿ such thatc(P)<c(2 ⁿ ); (iv) for every positive integern there is a positive integerN such that, ifB _m is contained in a partially ordered set having then-cutset property, thenm?N.