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.     

A tight Hermite–Hadamard inequality and a generic method for comparison between residuals of inequalities with convex functions

Periodica Mathematica Hungarica - We present a tight parametrical Hermite–Hadamard type inequality with probability measure, which yields a considerably closer upper bound for the mean value...     

Nonlinear frequency response analysis: a recent review and perspectives

The nonlinear frequency response analysis (NFRA) can be seen as an extension of electrochemical impedance spectroscopy. NFRA gives a full and detailed representation of the system response and can establish a connection between model parameters and the experimentally observed phenomena. In this article, different theoretical NFRA approaches and the most recent application examples are discussed. A simple electrochemical example is used to showcase the benefits and disadvantages of analyzing the system response by using different approaches. In addition, it was shown how to extract experimental harmonic values and analyze them.     

Sensitivity analysis for discrete optimal control problems

We present local sensitivity analysis for discrete optimal control problems with varying endpoints in the case when the customary regularity of boundary conditions can be violated. We study the behavior of the optimal solutions subject to parametric perturbations of the problem.