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.

     

Creation, Dissipation and Recycling of Resources in Non-Equilibrium Systems

In this article, we define stochastic dynamics for a system coupled to reservoirs. The rules for forward and backward transitions are related by a generalized detailed balance identity involving the system and its reservoirs. We compare the variation of information and of entropy. We define the Carnot dissipation and prove that it can be expressed in terms of cyclic transformations. Lower bounds for partial dissipations are also studied, as well as the effect of switching off certain reservoirs. We also study the near degeneracy of the stochastic matrix, relate it to phase transitions and we show that the reduced dynamics on the set of phases is a permutation. Finally, we relate these concepts to heat, work and more generally to the dissipation and creation of resources, in general systems.     

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.     

Fairness in Scheduling

On-line machine scheduling has been studied extensively, but the fundamental issue of fairness in scheduling is still mostly open. In this paper we explore the issue in settings where there are long-lived processes which should be repeatedly scheduled for various tasks throughout the lifetime of a system. For any such instance we develop a notion ofdesiredload of a process, which is a function of the tasks it participates in. Theunfairnessof a system is the maximum, taken over all processes, of the difference between the desired load and the actual load.An example of such a setting is thecarpool problemsuggested by Fagin and Williams [IBM Journal of Research and Development27(2) (1983), 133–139]. In this problem, a set ofnpeople form a carpool. On each day a subset of the people arrive and one of them is designated as the driver. A scheduling rule is required so that the driver will be determined in a “fair” way.We investigate this problem under various assumptions on the input distribution. We also show that the carpool problems can capture several other problems of fairness in scheduling.     

The efficacy of tilted axial MRI of the CNS

The angle between the straight axial plane and the orbito-meatal line was measured in 156 consecutive magnetic resonance examinations. Inconsistent head positioning caused this angle to vary by as much as 44 degrees. Careful positioning of the patient by the technologist can minimize this variability, leading potentially to improved image interpretation. To assess the merit of a standardized orientation for MR examinations of the head, straight axial and tilted axial MR scans were compared in 34 patients. The tilted images were obtained parallel to the orbito-meatal line and were found to be superior for visualization of the cerebellum. When correlative x-ray CTs are available or when an abnormality in the posterior fossa is suspected, tilted axial MR scans should be employed.     

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.