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.     

An optodynamic method for the real-time determination of the depth of a laser-drilled hole

An experimental method for determining the real-time depth of laser-drilled holes is presented. The proposed method involves detecting the laser-induced optoacoustic waves generated during the interaction of the laser beam with the material. Our optodynamic study involved measuring the propagation times of these waves as they traveled through the material and analyzing their temporal behavior during the drilling process. The experimental observations revealed an exponential relationship between the propagation time of the longitudinal stress wave and the number of consecutive laser pulses. Received: 25 October 2001 / Accepted: 27 October 2001 / Published online: 20 December 2001     

Fast electrons generation by RF and random fields near the antenna I. One dimensional model and regular fields

Test particle motion and acceleration has been explored in strong radio frequency (RF) fields, for which quasilinear ponderomotive force approximation is not valid. By nonlinear acceleration in spatially varying wave amplitude of RF travelling wave, electrons may be accelerated to time averaged velocities significantly larger than the RF wave phase velocity, and than the boundary plasma thermal velocity, in RF fields of several Volts per centimeter at wave frequency of 7 MHz. It is also demonstrated that even weak spatial gradients, much weaker than those expected in experiments, of the RF wave field amplitude, have significant consequences for the particle motion. Estimates are presented of the total energy transferred from the near antenna RF field to the plasma due to the nonlinear electron acceleration effects.     

Transient binary nucleation from ethanol-hexanol vapour

We study condensation of ethanol-hexanol vapour by numerical solution of kinetic equations. The number of droplets formed in unit volume is computed within self-consistent classical model. It is shown that formation of ethanol-rich droplets prevails at the initial stage of nucleation process, but in the stationary state formation of droplets near the saddle point (on cluster formation energy surface) plays the dominant role. Presented at the 6th Joint Seminar “Development of Materials Science in Research and Education”, Karlštejn, Czech Republic, 17–19 September 1996. This work was supported by Grant No. A1010615 of the Grant Agency of the Academy of Sciences of the Czech Republic.     

Quantum Interference, Quantum Theory of Measurement, and (In)completeness of Quantum Mechanics

The new techniques and ideas in quantum interferometry with neutrons, photons, atoms, electrons, and Bose condensates that fluorished in the last two decades have influenced in a decisive way the thinking and the research in the foundations and interpretation of quantum mechanics. The controversies existing among different schools on the reality of matter waves of quantum theory, the postulates of quantum measurement theory, and the (in)completeness of quantum mechanics have to be approached now in a new way. Our argumentation follows the spirit of the Paris school.     

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