Ionization Suppression and Recovery in Direct Biofluid Analysis Using Paper Spray Mass Spectrometry

Paper spray mass spectrometry is a method for the direct analysis of biofluid samples in which extraction of analytes from dried biofluid spots and electrospray ionization occur from the paper on which the dried sample is stored. We examined matrix effects in the analysis of small molecule drugs from urine, plasma, and whole blood. The general method was to spike stable isotope labeled analogs of each analyte into the spray solvent, while the analyte itself was in the dried biofluid. Intensity of the labeled analog is proportional to ionization efficiency, whereas the ratio of the analyte intensity to the labeled analog in the spray solvent is proportional to recovery. Ion suppression and recovery were found to be compound- and matrix-dependent. Highest levels of ion suppression were obtained for poor ionizers (e.g., analytes lacking basic aliphatic amine groups) in urine and approached –90%. Ion suppression was much lower or even absent for good ionizers (analytes with aliphatic amines) in dried blood spots. Recovery was generally highest in urine and lowest in blood. We also examined the effect of two experimental parameters on ion suppression and recovery: the spray solvent and the sample position (how far away from the paper tip the dried sample was spotted). Finally, the change in ion suppression and analyte elution as a function of time was examined by carrying out a paper spray analysis of dried plasma spots for 5 min by continually replenishing the spray solvent.

Open image in new window

Graphical Abstract ?

     

Synthesis and metal cation complexing properties of crown-annelated terthiophenes containing 3,4-ethylenedioxythiophene

Macrocyclic systems derived from crown-annelated terthiophene involving a median EDOT unit have been synthesized by coupling diiodooligooxyethylene chains and bis(2-cyanoethylsulfanyl)terthiophene under high dilution conditions. The metal cation complexing properties of the compounds have been analyzed using 1H NMR, UV-vis spectroscopy, and cyclic voltammetry. These various experiments provide consistent results showing that one of the compounds exhibits interesting complexing properties for Pb2+.     

Bulky Polyfluorinated Terphenyldiphenylboranes: Water Tolerant Lewis Acids

Protocols for the synthesis of the bulky polyfluorinated triarylboranes 2,6-(C₆F₅)₂C₆F₃B(C₆F₅)₂ ( 1 ), 2,6-(C₆F₅)₂C₆F₃B[3,5-(CF₃)₂C₆H₃] ( 2 ), 2,4,6-(C₆F₅)₃C₆H₂B(C₆F₅)₂ ( 3 ), 2,4,6-(C₆F₅)₃C₆H₂B[3,5-(CF₃)₂C₆H₃] ( 4 ) were developed. All boranes are water tolerant and according to the Gutmann-Beckett method, 1 – 3 display Lewis acidities larger than that of the prominent B(C₆F₅)₃.     

Large solutions of elliptic equations with a weakly superlinear nonlinearity

This paper studies the asymptotic behavior near the boundary for large solutions of the semilinear equation Δu + au = b(x)f(u) in a smooth bounded domain Ω of ℝ^N with N ≥ 2, where a is a real parameter and b is a nonnegative smooth function on . We assume that f(u) behaves like u(ln u)^α as u → ∞, for some α > 2. It turns out that this case is more difficult to handle than those where f(u) grows like u ^p (p > 1) or faster at infinity. Under suitable conditions on the weight function b(x), which may vanish on ∂Ω, we obtain the first order expansion of the large solutions near the boundary. We also obtain some uniqueness results. Research of both authors supported by the Australian Research Council.     

Stereochemical Communication within a Chiral Ion Pair Catalyst

Ionic interactions are increasingly appreciated as a key, asymmetry‐inducing factor in enantioselective catalytic transformations, including those involving Brønsted acid or base catalysis, phase‐transfer catalysis, and related processes. However, a detailed understanding of these interactions is often lacking. Herein, we show how an enantiopure anion enforces a chiral conformation onto a catalytically relevant achiral cation. Specifically, we use vibrational circular dichroism (VCD) spectroscopy to monitor the transmission of stereochemical information from a chiral phosphate anion to a flexible manganese(III)–salen cation. We show that VCD can be used to study solvent effects and that the obtained chiroptical data directly and quantitatively correlate with the experimentally observed enantioselectivity in an asymmetric olefin epoxidation reaction.     

Flow due to a plate that applies an accelerated shear to a second grade fluid between two parallel walls perpendicular to the plate

The velocity field and the shear stresses corresponding to the motion of a second grade fluid between two side walls, induced by an infinite plate that applies an accelerated shear stress to the fluid, are determined by means of the integral transforms. The obtained solutions, presented under integral form in term of the solutions corresponding to the flow due to a constant shear on the boundary, satisfy all imposed initial and boundary conditions. In the absence of the side walls, they reduce to the similar solutions over an infinite plate. The Newtonian solutions are obtained as limiting cases of the general solutions. The influence of the side walls on the fluid motion as well as a comparison between the two models is shown by graphical illustrations.     

Regioselective orthopalladation of (Z)-2-aryl-4-arylidene-5(4H)-oxazolones: scope, kinetico-mechanistic, and density functional theory studies of the C-H bond activation

Orthopalladated complexes derived from (Z)-2-aryl-4-arylidene-5(4H)-oxazolones have been prepared by reaction of the oxazolone with palladium acetate in acidic medium. The reaction is regioselective, only the ortho C-H bond of the arylidene ring being activated, producing a six-membered ring. The scope and reaction conditions of the orthopalladation are dependent on the acidity of the solvent. In CF(3)CO(2)H a large number of oxazolones can be metalated under mild conditions. As acidity decreases a lesser number of oxazolones can be efficiently palladated and harsher conditions must be used to achieve similar yields. The C-H bond activation in acidic medium agrees with an ambiphilic mechanism, as determined from kinetic measurements at variable temperature and pressure for different oxazolones substituted at the arylidene ring. The mechanism has been confirmed by density functional theory (DFT) calculations, where the formation of the six-membered ring is shown to be favored from both a kinetic and a thermodynamic perspective. In addition, the dependence of the reaction rate on the acidity of the medium has also been accounted for via a fine-tuning between the C-H agostic precoordination and the proton abstraction reaction in the overall process occurring on coordinatively saturated [Pd(κ(N)-oxazolone)(RCO(2)H)(3)](2+).     

High-performance separation techniques hyphenated to mass spectrometry for ganglioside analysis

Gangliosides, sialic-acid-containing glycosphingolipids are involved in numerous biological processes and play essential roles in severe pathologies, with predilection in those of the central nervous system. Formerly, ganglioside composition and quantity were assessed exclusively by thin-layer chromatographic (TLC), immunochemical, and immunohistochemical methods, which have limited effectiveness being unable to detect minor components in mixtures of high heterogeneity. Increased awareness of the biological importance of gangliosides stimulated the development of analytical methods that are better amenable to complex ganglioside mixtures. More recently, MS in online conjunction with high-performance separation techniques brought a significant progress to the field. This review highlights the state-of-the-art development and application of separation methods online coupled to MS for ganglioside analysis. Most original and successful protocols based on GC-MS, LC-MS, and CE-MS are presented here together with the special instrumental and sample preparation requirements to be met for effective ganglioside separation, detection, and structural identification. Finally, the advantages and downsides of each methodology as well as the perspectives for simplification, standardization, and upgrading are assessed.     

Thermal behavior of verapamil in pure and in solid dosage forms

Verapamil is a phenyl-alchil-amine type pharmaceutical largely used as a specific calcium antagonist. Knowledge of drug-excipient compatibility represents an important phase in development of different dosage forms. Hyphenated techniques are versatile for obtaining such necessary information’s. The TG/DTG/DTA curves were obtained in air at different heating rates and in nitrogen. The IR spectra of pure compound and its char at 400 °C (by U-ATR technique) and the IR identification of Evolved Gasses allowed some discussions on the thermally induced events. In the solid dosage forms verapamil was mixed with talc, magnesium stearate, starch, and cellulose, and the corresponding thermoanalytical curves were compared with that one of pure I. No physical or chemical interactions were observed till 250 °C. A kinetic analysis was performed for TG step of verapamil between 250 and 350 °C. The data at four heating rates (7, 10, 12, 15 °C min⁻¹) were processed on a strategy using at last three different kinetic methods. For these, the NPK method seems to be less speculative, allowing an objective determination of the kinetic parameters.