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.

     

Nickel/Photoredox-Catalyzed Asymmetric Reductive Cross-Coupling of Racemic α-Chloro Esters with Aryl Iodides

A unique nickel/organic photoredox co-catalyzed asymmetric reductive cross-coupling between α-chloro esters and aryl iodides is developed. This cross-electrophile coupling reaction employs an organic reductant (Hantzsch ester), whereas most reductive cross-coupling reactions use stoichiometric metals. A diverse array of valuable α-aryl esters is formed under these conditions with high enantioselectivities (up to 94 %) and good yields (up to 88 %). α-Aryl esters represent an important family of nonsteroidal anti-inflammatory drugs. This novel synergistic strategy expands the scope of Ni-catalyzed reductive asymmetric cross-coupling reactions.     

A Noninvasive, on Wafer Method to Determine the Intrinsic Stress of a Polymer Layer

The method described in this paper allows an investigator to determine the intrinsic stress of a polymer layer in a way that does not result in damage to devices or test structures. The method requires that a small area of the polymer be released from the substrate to form a diaphragm. The diaphragm is stimulated with acoustic white noise and the diaphragm movement is monitored with a laser vibrometer. The first few resonance frequencies of the diaphragm are obtained using a laser vibrometer and then those frequencies are used to calculate the membrane intrinsic bi-axial tension.     

Counting unrooted maps on the plane

A planar map is a 2-cell embedding of a connected planar graph, loops and parallel edges allowed, on the sphere. A plane map is a planar map with a distinguished outside (“infinite”) face. An unrooted map is an equivalence class of maps under orientation-preserving homeomorphism, and a rooted map is a map with a distinguished oriented edge. Previously we obtained formulae for the number of unrooted planar n-edge maps of various classes, including all maps, non-separable maps, eulerian maps and loopless maps. In this article, using the same technique we obtain closed formulae for counting unrooted plane maps of all these classes and their duals. The corresponding formulae for rooted maps are known to be all sum-free; the formulae that we obtain for unrooted maps contain only a sum over the divisors of n. We count also unrooted two-vertex plane maps.     

The effect of olefinic terminal chains on the mesomorphic properties of 4,4'-disubstituted diphenyldiacetylenes

New diphenyldiacetylenes of the type with A, B = H and/or F; m = 0, 1; n = 1-4; and X = C n H 2n + 1 , F, CF 3 or CN were synthesized and their mesomorphic properties determined by hot stage polarizing microscopy and DSC. When m = 0, all of these compounds showed only a nematic phase except when X = CF 3 when both nematic and smectic A phases were seen. Both clearing and melting temperatures were higher than those reported for substitution with the corresponding alkyl chains but the much larger increase in clearing temperatures produced considerably wider nematic phases. Eutectic mixtures of a few of these olefins yielded nematic materials also having much wider temperature ranges and higher clearing temperatures than the eutectic mixtures of the alkyl compounds, while retaining their high birefringence and low viscosities. Such materials are of interest for beam-steering devices.

Four of the diacetylenes with m = 1 ( A, B = H) were also prepared ( X = C 6 H 13 , F, n = 2, 3). When X was C 6 H 13 ( n = 2), the nematic range was smaller in the 2- than in the 1-olefin but wider than in the alkyl series. When X = F, either no nematic phase or a monotropic one was observed, whereas the 1-olefins gave a much wider nematic phase. Both transition temperatures were lower than those for the corresponding 1-olefin and alkyl analogues. The compound with X = C 6 H 13 and n = 2 had a melting temperature below room temperature.