A rapid and sensitive bioanalytical LC–MS/MS method for the quantitation of a novel CDK5 inhibitor 20–223 (CP668863) in plasma: Application to in vitro metabolism and plasma protein-binding studies

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (MS/MS) method was developed and validated for the quantitation of the novel CDK5 inhibitor ‘20–223' in mouse plasma. Separation of analytes was achieved by a reverse-phase ACE Excel C₁₈ column (1.7 μm, 100 × 2.1 mm) with gradient elution using 0.1% formic acid (FA) in methanol and 0.1% FA as the mobile phase. Analytes were monitored by MS/MS with an electrospray ionization source in the positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range 0.2–500 ng/mL for 20–223. The within- and between-batch precision were within the acceptable limits as per Food and Drug Administration guidelines. The validated method was successfully applied to plasma protein binding and in vitro metabolism studies. Compound 20–223 was highly bound to mouse plasma proteins (>98% bound). Utilizing mouse S9 fractions, in vitro intrinsic clearance (CL_int) was 24.68 ± 0.99 μL/min/mg protein. A total of 12 phase I and II metabolites were identified with hydroxylation found to be the major metabolic pathway. The validate method required a low sample volume, was linear from 0.2 to 500 ng/mL, and had acceptable accuracy and precision.     

Comparison of the growth and degradation of poly(glycolic acid) and poly(ε‐caprolactone) brushes

The growth and degradation of poly(glycolic acid) (PGA) and poly(ε‐caprolactone) (PCL) brushes were compared. Using tin (octanoate) as the catalyst, optimal conditions were found for growth of each polyester brush from the hydroxy‐terminated silicon surface via ring‐opening polymerization. PCL brushes grew thicker at elevated temperatures but the thickest PGA brushes grew at room temperature. Unlike bulk polyesters that can degrade under both acidic and basic conditions, the confined surface polyester brushes only degraded under neutral or basic conditions. The degradation mechanism of grafted polyester brushes was probed through a blocking test. It was shown that the terminal hydroxy groups of these polyester brushes were essential to the degradation process indicating a preferential backbiting mechanism. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4643–4649     

Scaling Limits for Width Two Partially Ordered Sets: The Incomparability Window

We study the structure of a uniformly randomly chosen partial order of width 2 on n elements. We show that under the appropriate scaling, the number of incomparable elements converges to the height of a one dimensional Brownian excursion at a uniformly chosen random time in the interval [0, 1], which follows the Rayleigh distribution.     

Shear thickening and shear-induced agglomeration of chemical mechanical polishing slurries using electrolytes

Chemical mechanical polishing is a fundamental technology used in the semiconductor manufacturing industry to polish and planarize a wide range of materials for the fabrication of microelectronic devices. During the high-shear (～1,000,000 s^?1) polishing process, it is hypothesized that individual slurry particles are driven together to form large agglomerates (≥0.5 µm). These agglomerates are believed to trigger a shear-induced thickening effect and cause defects during polishing. We examined how the addition of various monovalent salts (CsCl, KCl, LiCl, and NaCl) and electrostatic stabilizing bases (KOH, NaOH, or CsOH) influenced the slurry’s thickening behavior. Overall, as the added salt concentration was increased from 0.02 to 0.15 M, the shear rate at which the slurry thickened (i.e., the critical shear rate) decreased. Slurries with added CsCl, NaCl, and LiCl thickened at comparable shear rates (～20,000–70,000 s^?1) and, in general, followed ion hydration theory (poorly hydrated ions caused the slurry to thicken at lower shear rates). However, slurries with added KCl portrayed thickening behavior at higher critical shear rates (～35,000–100,000 s^?1) than other chloride salts. Also, slurries stabilized with CsOH thickened at higher shear rates (～90,000–140,000 s^?1), regardless of the added salt cation or concentration, than the slurries with KOH or NaOH. The NaOH-stabilized slurries displayed thickening at the lowest shear rates (～20,000 s^?1). The thickening dependence on slurry base cation indicates the existence of additional close-range structure forces that are not predicted by the Derjaguin–Landau–Verwey–Overbeek colloidal stability theory.     

Preparation of sinapinaldehyde modified mesoporous silica materials and their application in selective extraction of trace Pb(II)

A new solid phase extractant, sinapinaldehyde (SA) modified SBA-15 mesoporous silica, was developed for selective extraction and preconcentration of trace Pb(II) from aqueous solutions. The successful immobilization of SA on SBA-15 and the strong interaction between SA-SBA-15 and Pb(II) were characterized and confirmed by FTIR spectroscopy and scanning electron microscopy. Parameters such as solution pH, shaking time, eluent condition and sample volume were optimized so that the maximum removal of Pb(II) from solution could be achieved. At pH 4.0, the maximum adsorption capacity of the sorbent for Pb(II) was found to be 33.6?mg?g^?1 and the adsorbed Pb(II) could be completely eluted using a mixed solution of 2?M HCl and 5% CS(NH₂)₂. Some common metal ions such as K(I), Na(I), Mg(II), Ca(II), Cr(III), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) did not interfere with the adsorption of trace Pb(II). The detection limit of the present method was found to be 1.3?ng?mL^?1 and the relative standard deviation was less than 2.0% (n?=?8). These results suggested that this new sorbent is very efficient and selective for the removal of trace Pb(II) in water samples.     

On Random Field Induced Ordering in the Classical <Emphasis Type="Italic">XY</Emphasis> Model

Consider the classical XY model in a weak random external field pointing along the Y axis with strength ε. We study the behavior of this model as the range of the interaction is varied. We prove that in any dimension d≥2 and for all ε sufficiently small, there is a range L=L(ε) so that whenever the inverse temperature β is larger than some β(ε), there is strong residual ordering along the X direction.     

Collinear laser spectroscopy with reverse-extracted bunched beams at TRIUMF

Collinear laser spectroscopy with reverse-extracted cooled bunched beams was performed at TRIUMF with radioactive ion beams. Surface-ionized ^78,78mRb ions were injected into TITAN??s cooler-buncher, and reverse-extracted to the laser beam line. There they were neutralised and excited with a counter-propagating laser beam. The fluorescence signal from the D ₂ line was recorded with a photomultiplier tube. The cooler provided typically 50 ion bunches per second, with each bunch containing approximately 10⁵ ions, temporally distributed with a 1.6 ??s width. A hardware gate was set on the signal, suppressing the background by four orders of magnitude.     

Total synthesis of lansiumamides A and B and alatamide

The total syntheses of lansiumamide A, lansiumamide B and alatamide have been completed taking advantage of the dihalo-olefination of N-formylimides. The syntheses are convergent, flexible and allow for the generation of analogues not accessible through other routes.     

Lower-rim versus upper-rim functionalization in di-ionizable calix[4]arene-crown-5 isomers. Synthesis and divalent metal ion extraction

Two series of di-ionizable calix[4]arene-crown-5 isomers in the cone conformation are synthesized to probe the effect of the pendant acidic group location on their metal ion extraction properties. In one series, the ionizable groups are attached to the lower rim of the calix[4]arene scaffold, which orients them near the crown ether cavity. In the second series, the ionizable groups are connected to the upper rim positioning them away from the crown ether ring, but close to the hydrophobic pocket of the calix[4]arene unit. The metal ion extraction behaviors of the two series of ligands are compared in extractions of alkaline earth metal cations, Hg²⁺, and Pb²⁺.     

The impact of comet Shoemaker-Levy 9 on Jupiter

We have performed computational shock-physics simulations of the hypervelocity (60 km/s) impact of 1–3 km, water-ice spheres entering a hydrogen-helium Jovian atmosphere. These conditions simulate the best current estimates for the collision of fragments of periodic comet Shoemaker-Levy 9 with Jupiter in July, 1994. We used the Eulerian shock-physics code CTH, and its parallel version PCTH to perform 2-D analyses of penetration and breakup, and 3-D analyses of the growth of the resulting fireball during the first 100 seconds after fragment entry. We can use our simulations to make specific predictions of the time interval between fragment entry and fireball arrival into line-of-sight from the earth. For a fragment larger than about 1 km, we believe that the time of fireball arrival above Jupiter's limb will be directly observable from earth. Measurements of this time by observers, in conjunction with our simulations, may allow mass of cometary fragments to be determined.This article was processed using Springer-Verlag T_EX Shock Waves macro package 1.0 and the AMS fonts, developed by the American Mathematical Society.