Sensitive CE-MS method for monitoring of riociguat and desmethylriociguat levels in human serum

Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10–1000 ng/mL), with adequate accuracy (90.1–114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.     

Why and how to avoid standard kinetic equations I. Principles and band conduction problem

A review of ideas leading to full rejection of any finite or partially-infinite order kinetic equation linearized in external field is given on grounds of the time-convolution Generalized Master Equations (GME). By two examples (two-level and band conduction problem), it is shown how standard kinetic equations result from GME in the lowest order approximations which obscure, however, a direct correspondence with the Kubo linear response theory. Without approximations, on the other hand, the rigorous approach is shown to be fully equivalent with the Kubo results. It is argued and illustrated that usual technical simplicity and seeming physical lucidity of standard theories (connected with the presence of field-independent transfer or scattering rates in the fielddependent linearized theory) are just owing to structural features which are solely due to the lowest order approximations involved. These features (i.e. also the possibility of standard physical interpretation of kinetic phenomena) are proved to disappear completely as far as the theory goes properly to higher orders.     

Global Analysis of the Flows of Fluids with Pressure-Dependent Viscosities

 To describe the flows of fluids over a wide range of pressures, it is necessary to take into account the fact that the viscosity of the fluid depends on the pressure. That the viscosity depends on the pressure has been verified by numerous careful experiments. While the existence of solutions local-in-time to the equations governing the flows of such fluids are available for small, special data and rather unrealistic dependence of the viscosity on the pressure, no global existence results are in place. Our interest here is to establish the existence of weak solutions for spatially periodic three-dimensional flows that are global in time, for a large class of physically meaningful viscosity-pressure relationships. (Accepted May 1, 2002) Published online November 15, 2002 Communicated by S. S. ANTMAN     

A Simple Bi-directional Mode Expansion Propagation Algorithm Based on Modes of a Parallel-plate Waveguide

The bi-directional mode expansion propagation algorithm (BEP) is known to be an accurate and efficient method for modelling field distribution in high-index contrast waveguide structures with strong back-reflections like Bragg gratings and photonic crystals. The main difficulty of this method is that for lossy structures, the propagation constants of modes are to be searched in the complex plane. To speed-up this procedure, a two-step algorithm for eigenmode calculation based on the expansion into the modes of an empty metallic waveguide has recently been proposed. Proper truncation rules possessing good convergence of the expansion method for both TE and TM modes have also been recently published. In this contribution, both these approaches are combined in the development of an extremely simple version of the two-dimensional BEP method that makes use of the field expansion into the eigenmodes of a parallel-plate waveguide. The method is strictly reciprocal and appeared to be computationally reliable also for strongly lossy structures. High numerical stability is ensured using the scattering matrix formalism, and an efficient method of calculating Bloch modes for symmetric as well as asymmetric periodic waveguide structures is adopted. A wide range of applicability of the method is demonstrated by a few examples.     

The Discounted Limit Theorems

The large deviation theorems, exponential inequalities and a non-uniform estimate of the Berry–Esséen theorem in a discounted version are proved.Dedicated to Professor Vytautas Statulevičius on the occasion of his 75th birthday.     

Discrete limit theorems for general Dirichlet series. III

Here we prove a limit theorem in the sense of the weak convergence of probability measures in the space of meromorphic functions for a general Dirichlet series. The explicit form of the limit measure in this theorem is given. Partially supported by Lithuanian Foundation of Studies and Science     

An expansion in the exponent for compound binomial approximations

The purpose of this paper is two-fold. First, we introduce a new asymptotic expansion in the exponent for the compound binomial approximation of the generalized Poisson binomial distribution. The dependence of its accuracy on the symmetry and shifting of distributions is investigated. Second, for compound binomial and compound Poisson distributions, we present new smoothness estimates, some of which contain explicit constants. Finally, the ideas used in this paper enable us to prove new precise bounds in the compound Poisson approximation. Published in Lietuvos Matematikos Rinkinys, Vol. 46, No. 1, pp. 67–110, January–March, 2006.