Validation and application of a high-performance liquid chromatography/tandem mass spectrometry assay for sumatriptan in human plasma

A sensitive and convenient high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) assay is described for the (5-HT(lB/lD)) receptor agonist sumatriptan in human plasma. Sumatriptan was recovered from plasma (81.8 +/- 6.8%) by liquid-liquid extraction. The mobile phase flow rate was 0.3 mL/min and consisted of methanol:water:formic acid (90:10:0.1, v/v/v). The analytical column (4.6 x 100 mm) was packed with Partisil C(8) (5 micro m). The standard curve was linear from 0.7 to 70.4 ng/mL (r(2) > 0.99). The lower limit of quantitation was 0.7 ng/mL. The assay was specific, accurate (percentage deviation from nominal concentrations were <15%), precise and reproducible (within- and between-day coefficients of variation <10.3%). Sumatriptan in plasma was stable over three freeze/thaw cycles and at room temperature for one day. The utility of the assay was demonstrated by following sumatriptan plasma concentrations in two healthy subjects for 8-12 h following a single 20 mg intranasal dose.     

High performance liquid chromatographic-mass spectrometric assay for the quantitation of BMS-204352 in dog K(3)EDTA plasma

A high performance liquid chromatographic-mass spectrometric (LC/MS) assay was developed and validated for the determination of BMS-204352 in dog K(3)EDTA plasma. A 0.5 mL aliquot of control plasma was spiked with BMS-204352 and internal standard (IS) and buffered with 1 mL of 5 mM ammonium acetate. The mixture was then extracted with 3 mL of toluene. After separation and evaporation of the organic phase to dryness using nitrogen at 40 degrees C, the residue was reconstituted in the mobile phase and 25 microL of the sample were injected onto a Hypersil C(18) column (2 x 50 mm; 3 microm) at a flow rate of 0.5 mL/min. The mobile phase was consisted of two solvent mixtures (A and B). Solvent A was composed of 5 mM ammonium acetate and 0.1% triethylamine in 75:25 v/v water:methanol, pH adjusted to 5.5 with glacial acetic acid, and solvent B was 5 mM ammonium acetate in methanol. A linear gradient system was used to elute the analytes. The mass spectrometer was programmed to admit the de-protonated molecules at m/z 352.7 (IS) and m/z 357.9 (BMS-204352). Standard curves of BMS-204352 were linear (r(2) > or = 0.998) over the concentration range of 0.5-1000 ng/mL. The mean predicted quality control (QC) concentrations deviated less than 5.1% from the corresponding nominal values (ie 4, 80, 400 and 2000 ng/mL); the within- and between-assay precision of the assay were within 5.5% relative standard deviation. Stability of BMS-204352 was confirmed after at least three freeze/thaw cycles and BMS-204532 was stable in dog plasma when stored frozen at or below -20 degrees C for at least 16 weeks in spiked QC samples and for at least 4 1/2 weeks for in vivo study samples. BMS-204352 and IS were stable in the injection solvent at room temperature for at least 24 h. The assay was applied to delineate the pharmacokinetic disposition of BMS-204352 in dogs following a single intravenous dose administration. In conclusion, the assay is accurate, precise, specific, sensitive and reproducible for the pharmacokinetic analysis of BMS-204532 in dog plasma.     

Reaction of ethyl diazoacetate with Co3(CO)9(μ3-CCl): Isolation and X-ray structures of Co3(CO)9(μ3-CCO2Et), Co3(CO)9(μ3-CCH2CO2Et), and [Co3(CO)9(μ3-CCHCO2Et)]2

The reaction between the tricobalt cluster Co₃(CO)₉(₃-CCl) (1) and AlCl₃, followed by treatment with ethyl diazoacetate, N₂CHCO₂Et, affords a complex mixture of products in low yields. Column chromatography has allowed the isolation of the four cluster compounds Co₃(CO)₉(₃-CH) (2), Co₃(CO)₉(₃-CCO₂Et) (3), Co₃(CO)₉(₃-CCH₂CO₂Et) (4), and [Co₃(CO)₉(₃-CCHCO₂Et)]₂ (5). Clusters 4 and 5 are new and have been fully characterized in solution by IR and ¹H NMR spectroscopy. The molecular structures of clusters 3–5 have also been determined by single-crystal X-ray diffraction analysis. Co₃(CO)₉(₃-CCO₂Et) crystallizes in the triclinic space group P , a = 8.8393(5), b = 14.727(1), c = 15.272(1) Å, = 93.361(6), = 105.509(5)°, = 100.336(6)°, V = 1872.6(2) ų, Z = 4, and d _calc = 1.823 g/cm³. Co₃(CO)₉(₃-CCH₂CO₂Et) crystallizes in the monoclinic space group P2₁/n, a = 9.3806(7), b = 9.2617(8), c = 22.455(2) Å, = 94.483(7)°, V = 1944.9(3) ų, Z = 4, and d _calc = 1.803 g/cm³. [Co₃(CO)₉(₃-CCHCO₂Et)]₂ crystallizes in the monoclinic space group C2/c, a = 21.585(2), b = 8.7977(7), c = 20.784(1) Å, = 104.807(6)°, V = 3815.8(5) ų, Z = 4, and d _calc = 1.835 g/cm³. Plausible pathways leading to the formation of clusters 2, 4, and 5 are discussed.     

Generation of an arbitrary chirped microwave waveform with high time-bandwidth product for increasing range resolution of RADAR by using photonic technique

An approach for photonic generation of an arbitrary chirped microwave waveform with an increased time-bandwidth product (TBWP) is proposed and experimentally demonstrated. In the proposed model, light from the mode locked laser is splitted into two parts by using 1 × 2 power splitter: one is sent to linearly chirped fiber Bragg grating (LCFBG) through circulator and the other is time delayed by fiber delay line. The optical pulse in upper arm is time stretched by the LCFBG. Meanwhile, the optical pulse in lower arm experiences a time delay and then stretched by the dispersive single mode fiber. Temporal interference pattern is generated with an increasing or decreasing free spectral range by combination of two time-stretched optical pulses. Finally, the temporal interference pattern which is obtained at the output of optical coupler is transformed into an arbitrary chirped microwave waveform by using a photo-detector. The main advantage of this proposed model is high TBWP in the range of 750–1000 which ultimately results in an increased range resolution of radio detection and ranging.     

Tailoring a robust Al-MOF for trapping C2H6 and C2H2 towards efficient C2H4 purification from quaternary mixtures

Light hydrocarbon separation is considered one of the most industrially challenging and desired chemical separation processes and is highly essential in polymer and chemical industries. Among them, separating ethylene (C₂H₄) from C2 hydrocarbon mixtures such as ethane (C₂H₆), acetylene (C₂H₂), and other natural gas elements (CO₂, CH₄) is of paramount importance and poses significant difficulty. We demonstrate such separations using an Al-MOF synthesised earlier as a non-porous material, but herein endowed with hierarchical porosity created under microwave conditions in an equimolar water/ethanol solution. The material possessing a large surface area (793 m² g⁻¹) exhibits an excellent uptake capacity for major industrial hydrocarbons in the order of C₂H₂ > C₂H₆ > CO₂ > C₂H₄ > CH₄ under ambient conditions. It shows an outstanding dynamic breakthrough separation of ethylene (C₂H₄) not only for a binary mixture (C₂H₆/C₂H₄) but also for a quaternary combination (C₂H₄/C₂H₆/C₂H₂/CO₂ and C₂H₄/C₂H₆/C₂H₂/CH₄) of varying concentrations. The detailed separation/purification mechanism was unveiled by gas adsorption isotherms, mixed-gas adsorption calculations, selectivity estimations, advanced computer simulations such as density functional theory (DFT), grand canonical Monte Carlo (GCMC) and ab initio molecular dynamics (AIMD), and stepwise multicomponent dynamic breakthrough experiments.

Industrially important C₂H₄ purification from multi-component hydrocarbon mixtures.     

Secretion of human interleukin-2 fused with green fluorescent protein in recombinatn <Emphasis Type="Italic">pichia pastoris</Emphasis>

Methylotrophic yeast Pichia pastoris is convenient for the expression of eukaryotic foreign proteins owing to its potential for posttranslational modifications, protein folding, and facile culturing. In this work, human interleukin (hIL)-2 was successfully produced as a secreted fusion form in recombinant P. pastoris. By employing green fluorescent protein (GFP) as a monitoring fusion partner, clear identification of fusion protein expression and quantification of intracellular hIL-2 were possible even though there was no correlation between culture supernatant fluorescence and secreted hIL-2 owing to high media interference. Importantly, by the addition of casamino acids in basal medium, we were able to enhance threefold amount of secreted hIL-2, which was present both as a fusion and as a clipped fragment.     

Limits of translates of divergent geodesics and integral points on one-sheeted hyperboloids

For any non-uniform lattice Γ in SL₂(?), we describe the limit distribution of orthogonal translates of a divergent geodesic in Γ\SL₂(?). As an application, for a quadratic form Q of signature (2, 1), a lattice Γ in its isometry group, and v ₀ ∈ ?³ with Q(v ₀) > 0, we compute the asymptotic (with a logarithmic error term) of the number of points in a discrete orbit v ₀Γ of norm at most T, when the stabilizer of v ₀ in Γ is finite. Our result in particular implies that for any non-zero integer d, the smoothed count for the number of integral binary quadratic forms with discriminant d ² and with coefficients bounded by T is asymptotic to c · T log T + O(T).     

Direct measurements of local bed shear stress in the presence of pressure gradients

This paper describes the development of a shear plate sensor capable of directly measuring the local mean bed shear stress in small-scale and large-scale laboratory flumes. The sensor is capable of measuring bed shear stress in the range \(\pm\) 200 Pa with an accuracy up to \(\pm\) 1 %. Its size, 43 mm in the flow direction, is designed to be small enough to give spatially local measurements, and its bandwidth, 75 Hz, is high enough to resolve time-varying forcing. Typically, shear plate sensors are restricted to use in zero pressure gradient flows because secondary forces on the edge of the shear plate caused by pressure gradients can introduce large errors. However, by analysis of the pressure distribution at the edges of the shear plate in mild pressure gradients, we introduce a new methodology for correcting for the pressure gradient force. The developed sensor includes pressure tappings to measure the pressure gradient in the flow, and the methodology for correction is applied to obtain accurate measurements of bed shear stress under solitary waves in a small-scale wave flume. The sensor is also validated by measurements in a turbulent flat plate boundary layer in open channel flow.     

Limit distributions of expanding translates of certain orbits on homogeneous spaces

LetL be a Lie group and λ a lattice inL. SupposeG is a non-compact simple Lie group realized as a Lie subgroup ofL and . LetaεG be such that Ada is semisimple and not contained in a compact subgroup of Aut(Lie(G)). Consider the expanding horospherical subgroup ofG associated toa defined as U⁺ ={g&#x03B5;G:a ⁻ⁿ gaⁿ} →e as n → ∞. Let Ω be a non-empty open subset ofU ⁺ andn _i → ∞ be any sequence. It is showed that . A stronger measure theoretic formulation of this result is also obtained. Among other applications of the above result, we describeG-equivariant topological factors of L/gl × G/P, where the real rank ofG is greater than 1,P is a parabolic subgroup ofG andG acts diagonally. We also describe equivariant topological factors of unipotent flows on finite volume homogeneous spaces of Lie groups.