Eco-Friendly UPLC–MS/MS Method for Determination of a Fostamatinib Metabolite,Tamatinib, in Plasma: Pharmacokinetic Application in Rats

Fostamatinib is a prodrug of the active metabolite tamatinib, which is a spleen tyrosine kinase (Syk) inhibitor used in the treatment of primary chronic adult immune thrombocytopenia and rheumatoid arthritis. A highly sensitive, rapid, reliable, and green method was developed and validated using ultra-performance liquid chromatography and tandem mass spectrometry (UPLC–MS/MS) for quantification of tamatinib in rat plasma. Ibrutinib was used as internal standard and liquid–liquid extraction was applied using tert-butyl methyl ether. The analyte was separated on an Acquity^TM CSH C₁₈ (2.1 mm × 100 mm, 1.7 µm) column using mobile phase consisting of 10 mM ammonium acetate and acetonitrile (10:90) and the flow rate was 0.25 mL/min. Electrospray ionization (ESI) was carried out in positive mode. Quantitation of tamatinib and the IS was performed using multiple reaction monitoring mode with precursor-to-product transitions of m/z 471.1 > 122.0 and m/z 441.1 > 84.0, respectively. The calibration range was 0.1–1000.0 ng/mL and the linearity of the method was ≥0.997. The developed method greenness was investigated. All principal parameters for the method, including linearity, accuracy, precision, recovery, and stability, were within acceptable ranges. Tamatinib pharmacokinetic study in rats was successfully carried out using the developed method.     

Evaluation of plasma produced by first and second harmonic nano-second laser for enhancing the capability of laser induced breakdown spectroscopy technique

Evaluation of plasmas produced and optimized for improving the capability of convenential laser induced breakdown spectroscopy (LIBS) for analytical purposes of solid samples is the main goal of the present work. The plasma produced in the present study was generated by focusing a single nano-second Nd:YAG laser at the fundamental wavelength of 1064 nm and at the second harmonic wavelength of 532 nm on an Al target in air at atmospheric pressure. The emission spectrum was recorded time resolved over the whole UV-NIR (200–1000 nm) spectral range. This work describes an extension of previously reported studies and focuses now on the determination of the plasma parameters at the optimum condition – highest signal-to-noise ratio (SNR) and minimum limit of detection (LOD) — of the LIBS technique, which is now widely applied to the elemental analysis of materials in atmospheric air. Parameters of the produced plasma in the time interval from 0 to 10 μs are determined for to further understanding the LIBS plasma dynamics. O I and Mn I spectral lines are used in the present work as thermometric lines for the determination of the plasma temperature based on Boltzmann plots. Stark broadening of lines yields the electron density. The widths of the H _α -line at 656.27 nm, of the O I line at 844.65 nm, of Al II lines at 281.65 nm and 466.30 nm and of the Si I line at 288.15 nm has been utilized for that. The plasma temperature ranged from 0.73 eV to around 1 eV for the different laser energies with both laser wavelengths for the optimized plasma used for LIBS analysis. This temperature is very close to that well known for the other spectrochemical analytical techniques or in excitation sources such as inductively coupled plasma-optical emission spectrometry (ICP-OES).     

Thermal stability and crystallization kinetics of ternary Se–Te–Sb semiconducting glassy alloys

This paper presents the results of kinematical studies of glass transition and crystallization in glassy Se_85?x Te₁₅Sb _x (x = 2, 4, 6 and 8) using differential scanning calorimetry (DSC). From the dependence on heating rates of, the glass transition temperatures (T _g), and temperature of crystallization (T _p) the activation energy for glass transition (E _g) and the activation energy for crystallization (E _c) are calculated and their composition dependence can be discussed in term of the average coordination number and cohesive energy. The thermal stability of Se_85?x Te₁₅Sb _x was evaluated in terms of criterion ΔT = T _c ? T _g and kinetic criteria K(T _g) and K(T _p). By analyzing the crystallization results, the crystallization mechanism is characterized. Two (two- and three-dimensional growth) mechanisms are working simultaneously during the amorphous–crystalline transformation of the Se₈₃Te₁₅Sb₃ alloy while only one (three-dimensional growth) mechanism is responsible for the crystallization process of the chalcogenides Se_85?x Te₁₅Sb _x (x = 4, 6 and 8) glass. The phases at which the alloy crystallizes after the thermal process have been identified by X-ray diffraction.     

Investigating Algebraic and Logical Algorithms to Solve Hopf Bifurcation Problems in Algebraic Biology

Symbolic methods to investigate Hopf bifurcation problems of vector fields arising in the context of algebraic biology have recently obtained renewed attention. However, the symbolic investigations have not been fully algorithmic but required a sequence of symbolic computations intervened with ad hoc insights and decisions made by a human. In this paper we discuss the use of algebraic and logical methods to reduce questions on the existence of Hopf bifurcations in parameterized polynomial vector fields to quantifier elimination problems over the reals combined with the use of the quantifier elimination over the reals and simplification techniques available in REDLOG. We can reconstruct most of the results given in the literature within a few seconds of computation time and extend the investigations on these systems to previously not analyzed related systems. Especially we discuss cases in which one suspects that no Hopf bifurcation fixed point exists for biologically relevant values of parameters and system variables. Here we focus on logical and algebraic techniques of finding subconditions being inconsistent with the hypothesis of the existence of Hopf bifurcation fixed points.      

Synthesis of 5-spirocyclohexyl-2,4-dithiohydantoin derivatives: a potential anti-leishmaniasis agent

Abstract  

A series of spiro-dithiohydantoins were synthesized by heating a mixture of 5-spirocyclohexyl-2,4-dithiohydantoin potassium salt and 3-chloropropanoyl chloride. These compounds were synthesized and evaluated for their activity against five Leishmanial strains in the promastigote stage in vitro. Seventy-two hours inoculation of a variety of products gave an IC ₁₀₀ and average IC ₅₀ values of 1.25 and 0.376 mg/cm³ against all Leishmanial strains tested.     

Synthesis of 5-spirocyclohexyl-2,4-dithiohydantoin derivatives: a potential anti-leishmaniasis agent

Abstract  A series of spiro-dithiohydantoins were synthesized by heating a mixture of 5-spirocyclohexyl-2,4-dithiohydantoin potassium salt and 3-chloropropanoyl chloride. These compounds were synthesized and evaluated for their activity against five Leishmanial strains in the promastigote stage in vitro. Seventy-two hours inoculation of a variety of products gave an IC ₁₀₀ and average IC ₅₀ values of 1.25 and 0.376 mg/cm³ against all Leishmanial strains tested. Graphical Abstract   An erratum to this article can be found at     

Novel syntheses of some new 3,4-dihydrospiro{benzimidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridine-3,3′-indolin}-2′-one derivatives

Abstract  2-Methylbenzimidazole 1 reacted with 3-dicyanomethylidine-1-ethyl-2-oxoindoline 2 in ethyl acetate to afford 1-amino-2-cyano-3,4-dihydro-1′-ethylspiro{benzimidazo[1,2-a]pyridine-3,3′-indolin}-2′-one 6, which was used as a key intermediate in the synthesis of fused spiropolyheterocyclic derivatives of benzimidazopyridopyrimidine and/or benzimidazonaphthyridine nucleus incorporating an indoline moiety. Graphical abstract        

Conversion of novel palladacycles into oxopyrrolo[3,4-b]quinolines

The quinolinylcyclopalladated complexes 3a–b were synthesised in good yields (81% and 77%) by the insertion reaction of the prepared dinuclear palladium complexes [Pd(C,N-2-C₉H₄N-CHO-3-R-6)Cl(PPh₃)]₂ [(R = H (2a), R = OMe (2b)] with isonitrile XyNC (Xy = 2,6-Me₂C₆H₃). The cyclopalladated complexes 3a–b were also obtained in low yields (39% and 33.5%) via a one pot oxidative addition reaction of quinoline chloride 1a–b with isonitrile XyNC:Pd(dba)₂ (4:1). The reactions of 3a–b with Tl(TfO) (TfO = triflate, CF₃SO₃) in the presence of H₂O or EtOH causes depalladation reactions of the complexes to provide the corresponding organic compounds 4a–b, 5a–b and 6a–b in yields (41%, 27% and 18–19%). The products were characterized by satisfactory elemental analyses and spectral studies (IR, ¹H, ¹³C and ³¹P NMR). The crystal structures of 2a, 3a and 3b were determined by X-ray diffraction studies.     

Synthesis and spectroscopic properties of some new N,N'-disubstituted thiorueas of potential biological interest

Thirty-six new N,N'-disubstituted thioureas have been synthesized by the reaction of phenyl-, p-fluorophenyl- and benzoylisothiocyanates with various substituted anilines, aminopyridines and 4-aminoquinolines. The uv, ir and nmr spectral data are presented and discussed.