A novel,rapid and sensitive UPLC–MS/MS method for the determination of macitentan in patients with pulmonary arterial hypertension

Macitentan is an endothelin receptor antagonist commonly used in the treatment of pulmonary arterial hypertension (PAH). A novel, rapid, simple and sensitive UPLC–MS/MS method was developed and validated for pharmacokinetic study and the determination of macitentan in PAH patients. Macitentan and bosentan, which are used as internal standards, were detected using atmospheric pressure chemical ionization in positive ion and multiple reaction monitoring mode by monitoring the mass transitions m/z 589.1 → 203.3 and 552.6 → 311.5, respectively. Chromatographic separation was performed on a reverse‐phase C18 column (5 μm, 4.6 × 150 mm) with an isocratic mobile phase, which consisted of water containing 0.2% acetic acid–acetonitrile (90:10, v/v) at a flow rate of 1 mL/min. Retention times were 1.97 and 1.72 min for macitentan and IS, respectively. The calibration curve with high correlation coefficient (0.9996) was linear in the range 1–500 ng/mL. The lower limit of quantitation and average recovery values were determined as 1 ng/mL and 89.8%, respectively. This method is the first UPLC–MS/MS method developed and validated for the determination of macitentan from human plasma. The developed analytical method was fully validated for linearity, selectivity, specificity, accuracy, precision, sensitivity, stability, matrix effect and recovery according to US Food and Drug Administration guidelines. The developed method was applied successfully for pharmacokinetic study and the determination of macitentan in PAH patients.     

Kinetic and mechanistic features of carbon dioxide reforming of methane over Co–Ce/ZrO2 catalysts

Carbon dioxide reforming of methane (CDRM) is an effective route to utilize CO₂ and CH₄, the most abundant, thermodynamically stable and hazardous greenhouse gases. To overcome the economical impediments to favor CDRM's industrial applicability, its mechanistic features need to be revealed both for developing efficient catalysts and optimizing operational conditions. In this context, this work aims to obtain power-law type CDRM kinetic expressions over 5%Co–2%Ce/ZrO₂ and 10%Co–2%Ce/ZrO₂ catalysts and compare and analyze mechanistic routes to elucidate the effect of the Co:Ce ratio on kinetics. The empirical power-law type rate expressions were estimated with the reaction orders of 1.63 and 1.12 for CH₄ and 0.29 and –0.12 for CO₂ for 5%Co–2%Ce/ZrO₂ and 10%Co–2%Ce/ZrO₂ catalysts, respectively. Limited CH₄ activation and, thus, carbon formation due to low Co loading lead to accumulation of surface oxygen on ZrO₂ as redox ability of Ce becomes suppressed. This causes higher CO₂ activation barrier. The presence of H₂ in the feed slows down mechanistic steps involving CH_x. The reactions including CH₄ activation, most probably reversible direct CH₄ dissociation, are found to be rate determining.     

PM3 semiempirical study and its comparison with X-ray crystal structure of 4-[2-Methyl-4-(4-methoxyphenylazo)] phenoxyphtalonitrile

  The molecular and crystal structures of the title compound, C₂₂H₁₆N₄O₂, were determined by single crystal X-ray diffraction technique. The title compound crystallizes in monoclinic space group P1 2 ₁ /n1, with a=12.7811(9) ?, b=8.2002(4) ?, c=17.8772(14) ?, Z=4, D _calc=1.3112(1) g/cm³, μ (Mo-K_α)=0.087 mm⁻¹. The structure was solved by direct methods and refined to a final R=0.056 for 1891 reflections with I > 2σ (I). The asymmetric unit in the crystal structure contains only one neutral molecule. The positions of nitrogen atoms in the azo groups were disordered. There is no classic hydrogen bond in the crystal structure. The molecules in the crystal structure are stacked by π–π stacking and one edge-to-face interactions. In order to determine conformational flexibility and crystal packing effects on the molecules, molecular energy profile of the title compound was obtained with respect to the selected torsion angle, which is varied from −180° to +180° in every 10° via PM3 semi-empirical method.     

1,10-Phenanthroline-5,6-dione and 9,10-phenanthrenequinone as redox mediators for amperometric glucose biosensors

In this study, two ortho-quinoidal compounds, 1,10-phenanthroline-5,6-dione (PD) and 9,10-phenanthrenequinone (PQ), were examined as electron transfer mediators suitable for amperometric glucose biosensors. The dependences of the electrochemical responses of PD- and PQ-based amperometric glucose biosensors on varied concentrations of glucose were investigated under aerobic and anaerobic conditions. The PD-modified graphite rod (GR) electrode revealed a current response seven times higher than that of the PQ-modified GR electrode. The reactivity indices of ortho-quinoidals assessed by means of B3LYP functional method applying 6-311G(D) basis set showed that the electron-accepting potency for PD was markedly higher as compared with that of PQ. Compared to PQ, considerably higher reactivity of PD has been defined in the reactions with NADP⁺-ferredoxin reductase (FNR, EC 1.18.1.2) as a model single-electron transfer FAD-dependent enzyme, which provided an additional evidence for PD as a more efficient mediator compared to PQ. This study illustrates that PD can be applied as a redox mediator for glucose oxidase and it could be more suitable for a reagent-less biosensor design than PQ.     

Measurements of indoor radon concentration levels in Kilis,Osmaniye and Antakya,Turkey during spring season

The fact that 50% of the natural radiation dose to which humans are exposed is caused by radon gas makes indoor radon measurements important. In this study, levels of indoor radon gas were measured in 204 houses in Kilis, Osmaniye and Antakya using passive nuclear track detectors. Cr-39 radon detectors were left in the living rooms of participants’ houses, then analyzed at the Radon Laboratory of Health Physics Department in Çekmece Nuclear Research and Training Center (ÇANEM) of Atomic Energy Agency of Turkey (TAEK). Average indoor radon activity concentrations for Kilis, Osmaniye and Antakya were 50 Bq/m³ (1.26 mSv/y), 51 Bq/m³ (1.29 mSv/y) and 40 Bq/m³ (1.01 mSv/y), respectively.     

Chemical guiding of magnetic nanoparticles in dispersed media containing poly-(methylmethacrylate-co-vinylpyrrolidone)

The differential reactivity of methylmethacrylate (MMA) and vinylpyrrolidone (VP) in free radical copolymerization, with stirring in methanol, renders an emulsified two phase system. The dispersed and continuous liquid phases contain copolymers rich in MMA and VP, respectively. When Fe(3)O(4) magnetic nanoparticles (mNPs) stabilized with tetramethylammonium hydroxide are added to this emulsion, the mNPs are located in the continuous phase. Very small chemical changes in the methacrylic or vinylic chains are able to guide the mNP toward the interface or to the inside of the dispersed phase since quite a selective functionalization of each phase may be achieved separately. Thus, a small addition of methacrylic acid as comonomer (0.5% molar) guides all of the mNPs to the interface while a 0.5% molar of sulfopropyl methacrylate induces the migration of all mNPs to the dispersed phase. When 0.5% molar of a VP derivative bearing sulfonate functionality is added, the mNPs are found both in the interface and in the continuous phase. The addition of water allows solid MMA-based microspheres to be obtained incorporating the mNPs selectively either at the surface or in the core.     

A Differential Calculus on the (h,j)-Deformed Z3-Graded Superplane

In this work, Z₃-graded quantum (h, j)-superplane is introduced with a help of proper singular g matrix and a Z₃-graded calculus is constructed over this new h-superplane. A new Z₃-graded (h, j)-deformed quantum (super)group is constructed via the obtained calculus.     

On the univalence of an integral operator defined by Hadamard product

In this paper, we introduce a new general integral operator defined by the Hadamard product. Furthermore, we obtained new sufficient conditions for this operator to be univalent in the open unit disk.