Simultaneous determination of sibutramine and its active metabolites in human plasma by LC‐MS/MS and its application to a pharmacokinetic study

A simple and sensitive liquid chromatography–electrospray ionization–tandem mass spectrometry (LC‐ESI‐MS/MS) technique was developed and validated for the determination of sibutramine and its N‐desmethyl metabolites (M1 and M2) in human plasma. After extraction with methyl t‐butyl ether, chromatographic separation of analytes in human plasma was performed using a reverse‐phase Luna C₁₈ column with a mobile phase of acetonitrile–10 mm ammonium formate buffer (50:50, v/v) and quantified by ESI‐MS/MS detection in positive ion mode. The flow rate of the mobile phase was 200 μL/min and the retention times of sibutramine, M1, M2 and internal standard (chlorpheniramine) were 1.5, 1.4, 1.3 and 0.9 min, respectively. The calibration curves were linear over the range 0.05–20 ng/mL, for sibutramine, M1 and M2. The lower limit of quantification was 0.05 ng/mL using 500 μL of human plasma. The mean accuracy and the precision in the intra‐ and inter‐day validation for sibutramine, M1 and M2 were acceptable. This LC‐MS/MS method showed improved sensitivity and a short run time for the quantification of sibutramine and its two active metabolites in plasma. The validated method was successfully applied to a pharmacokinetic study in human. Copyright © 2011 John Wiley & Sons, Ltd.     

Signature invariants of covering links

We apply the theory of signature invariants of links in rational homology spheres to covering links of homology boundary links. From patterns and Seifert matrices of homology boundary links, we derive an explicit formula to compute signature invariants of their covering links. Using the formula, we produce fused boundary links that are positive mutants of ribbon links but are not concordant to boundary links. We also show that for any finite collection of patterns, there are homology boundary links that are not concordant to any homology boundary links admitting a pattern in the collection.

     

Nonlinear nanodevices using magnetic flux quanta

All devices realized so far that control the motion of magnetic flux quanta employ either samples with nanofabricated spatially-asymmetric potentials (which strongly limit controllability), or pristine superconductors rectifying with low-efficiency time-asymmetric oscillations of an external magnetic field. Using layered Bi2Sr2CaCu2O8+delta materials, here we fabricate and simulate two efficient nonlinear superconducting devices with no spatial asymmetry. These devices can rectify with high-efficiency a two-harmonic external current dragging vortices in target directions by changing either the relative phase or the frequency ratio of the two harmonics.     

Room-temperature broadband emission of an InGaAs/GaAs quantum dots laser

We report the first demonstration to our knowledge of an ultrabroad emission laser using InGaAs/GaAs quantum dots by cycled monolayer deposition. The device exhibits a lasing wavelength coverage of approximately 40 nm at an approximately 1160 nm center wavelength at room temperature. The broadband signature results from the superposition of quantized lasing states from highly inhomogeneous dots.     

Semiconductor Emitters in Entropy Sources for Quantum Random Number Generation

Random number generation (RNG) is needed for a myriad of applications ranging from secure communication encryption to numerical simulations to sports and games. However, generating truly random numbers can be elusive. Pseudorandom bit generation using computer algorithms provides a high random bit generation rate. Nevertheless, the reliance on predefined algorithms makes it deterministic and predictable once initial conditions are known. Relying on physical phenomena (such as measuring electrical noise or even rolling dice) can achieve a less predictable sequence of bits. Furthermore, if the physical phenomena originate from quantum effects, they can be truly random and completely unpredictable due to quantum indeterminacy. Traditionally, physical RNG is significantly slower than pseudorandom techniques. To meet the demand for high-speed RNG with perfect unpredictability, semiconductor light sources are adopted as parts of the sources of randomness, i.e., entropy sources, in quantum RNG (QRNG) systems. The high speed of their noise, the high efficiency, and the small scale of these devices make them ideal for chip-scale QRNG. Here, the applications and recent advances of QRNG are reviewed using semiconductor emitters. Finally, the performance of these emitters is compared and discuss their potential in future technologies.     

Computational aeroacoustics using the B-spline collocation method

One of the major problems in computational aero-acoustics is the disparity in length scales between the flow field and the acoustic field. As a result, a mapping function is normally used to achieve a non-uniform grid distribution. In this paper, a B-spline collocation method with an arbitrary grid placement capability is proposed. This capability not only allows an optimum grid distribution but also avoids the numerical complexities associated with the mapping function. The B-spline collocation method is applied to the case of spinning co-rotating vortices. The result agrees well with the matched asymptotic solution. To cite this article: R. Widjaja et al., C. R. Mecanique 333 (2005).     

Enantioselective Synthesis of Quaternary Carbon Stereocenters: Addition of 3‐Substituted Oxindoles to Vinyl Sulfone Catalyzed by Pentanidiums

A pentanidium‐catalyzed highly enantioselective conjugate addition of 3‐alkyloxindoles to phenyl vinyl sulfone has been demonstrated. This approach allows the construction of 3,3‐dialkyl‐substituted oxindole frameworks with high yield and excellent enantioselectivity (up to 99 %) under simple phase‐transfer conditions. A variety of oxindoles bearing all‐carbon quaternary stereogenic centers were obtained in the presence of 0.25 mol % pentanidium. Meanwhile, practicality was illustrated by a gram‐scale asymmetric synthesis of two 3,3‐dialkyl‐substituted oxindoles. The resulting adduct can be smoothly transformed to the natural product analogue in a short synthetic route.     

Fused Corrole Dimers Interconvert between Nonaromatic and Aromatic States through Two‐Electron Redox Reactions

A singly linked corrole dimer was synthesized by condensation of a dipyrromethane‐1‐carbinol with 1,1,2,2‐tetrapyrroethane. Oxidation of the dimer gave doubly linked corrole dimers 9 and 10 as the first examples of fused corrole dimers involving a meso–meso linkage. Dimers 9 and 10 exhibit characteristic ¹H NMR spectra, absorption spectra, excited‐state dynamics, and two‐photon absorption (TPA) values, which indicate the nonaromatic nature of 9 and the aromatic nature of 10 . Interestingly, 9 is fairly stable despite its unusual 2H‐corrole structure, which has been ascribed to the presence of two direct connections between the individual corrole units.