Enantioselective LC–ESI–MS/MS method for quantitation of (−)-lumefantrine and (+)-lumefantrine in mice plasma and application to a pharmacokinetic study

We developed and validated a simple, sensitive, selective, and reliable LC–MS/MS–ESI method for the direct quantitation of lumefantrine (LFN) enantiomers [(−)-LFN and (+)-LFN] in mice plasma as per regulatory guideline. LFN enantiomers and carbamazepine (internal standard) were extracted from mice plasma using Strata X SPE (solid-phase extraction) cartridges. Good resolution between enantiomers was achieved on a Chiralpak IA-3 column using an isocratic mobile phase (0.1% of diethyl amine in methanol), which was delivered at a flow rate of 0.8 mL/min. Detection and quantitation were performed using multiple reaction monitoring mode following the transitions m/z 530.27 → 512.30 and 237.00 → 194.00 for LFN enantiomers and the internal standard, respectively, in the positive-ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 2.39–895 ng/mL for each enantiomer. The intra- and inter-day precisions were in the range of 1.03–6.14 and 6.36–8.70 and 2.03–4.88 and 5.82–11.5 for (−)-LFN and (+)-LFN, respectively. Both (−)-LFN and (+)-LFN were found to be stable under different stability conditions. The method was successfully used to delineate stereoselective pharmacokinetics of LFN enantiomers in mice after an oral administration of rac-LFN (20 mg/kg). The pharmacokinetic results indicated that the disposition of LFN enantiomers was stereoselective in mice.     

Validated LC–MS/MS method for quantitation of a selective JAK1 inhibitor,filgotinib in rat plasma,and its application to a pharmacokinetic study in rats

Filgotinib is a selective JAK1 (Janus kinase) inhibitor, filed in Japan for the treatment of rheumatoid arthritis. In this paper, we report a validated liquid chromatography coupled with tandem mass spectrometry for the quantification of filgotinib in rat plasma using tofacitinib as an internal standard (IS) as per the Food and Drug Administration regulatory guidelines. Filgotinib and the IS were extracted from rat plasma using ethyl acetate as an extraction solvent and chromatographed using an isocratic mobile phase (0.2% formic acid:acetonitrile; 20:80, v/v) at a flow rate of 0.9 mL/min on a Gemini C₁₈ column. Filgotinib and the IS were eluted at ~1.31 and 0.89 min, respectively. The MS/MS ion transitions monitored were m/z 426.3 → 291.3 and m/z 313.2 → 149.2 for filgotinib and the IS, respectively. The calibration range was 0.78–1924 ng/mL. No matrix effect and carryover were observed. Intra- and inter-day accuracies and precisions were within the acceptance range. Filgotinib was stable for three freeze–thaw cycles: on bench-top up to 6 h, in an autosampler up to 21 h, and at −80 ° C for 1 month. This novel method has been applied to a pharmacokinetic study in rats.     

Probing Electronic Symmetry Reduction during Charge Migration via Time-Resolved X-Ray Diffraction

The present work focuses on probing ultrafast charge migration after symmetry-breaking excitation using ultrashort laser pulses. LiCN is chosen as prototypical system because it can be oriented in the laboratory frame and it possesses optically-accessible charge transfer states at low energies. The charge migration is simulated within the hybrid time-dependent density functional theory/configuration interaction framework. Time-resolved electronic current densities and simulated time-resolved x-ray diffraction signals are used to unravel the mechanism of charge migration. Our simulations demonstrate that specific choices of laser polarization lead to a control over the symmetry of the induced charge migration. Moreover, time-resolved x-ray diffraction signals are shown to encode transient symmetry reduction at intermediate times.     

Single-beam analysis of damaged beams: Comparison using Euler–Bernoulli and Timoshenko beam theory

A new general formulation that is applicable to the damaged, linear elastic structures ‘unified framework’ is used to obtain analytical expressions for natural frequencies and mode shapes. The term mode shapes is used to mean the displacement modes, the section rotation modes, the sectional bending strain modes and sectional shear strain modes. The formulation is applicable to damaged elastic self-adjoint systems. The formulation has two unique aspects: First, the theory is mathematically rigorous since no assumptions are made regarding the physical behavior at a damage location, therefore there is no need to substitute the damage with a hypothetical elastic element such as a spring. Since the beam is not divided at the damage location, rather than an 8 by 8, only a 4 by 4 matrix is solved to obtain the natural frequencies and mode shapes. Second, the inertia effects due to damage which have till now been neglected by researchers are accounted for. The formulation uses a geometric damage model, perturbation of mode shapes and natural frequencies, and a modal superposition technique to obtain and solve the governing differential equation. Timoshenko beam theory is then taken as an example, and its results are compared with results using Euler–Bernoulli beam theory and finite element models. The range of applicability of the two theories is ascertained for damage characteristics such as depth and extent of damage and beam characteristics such as slenderness ratio and Poisson?s ratio. The paper considers rectangular notch like non-propagating damage as an example of the damage.     

Designs of all-optical NOR gates using SOA based MZI

The paper investigates the non-linear behavior of semiconductor optical amplifier with Mach–Zehnder interferometer (SOA-MZI) configuration which makes it to work as a logic gate. The two designs of NOR gate based on SOA-MZI have been verified. The basic principal of both designs are same. The summation of data pulses have been taken and inverted to perform a NOR operation. In the design, the first 3 dB coupler creates a phase difference of π/2 in clock pulse and data pulse while passing through two interferometer arms. The clock and data pulses pass through SOA which attenuates the clock pulse wherever the data pulse is present. After passing through second 3 dB coupler a phase difference of π/2 is again created. Therefore, if the clock pulse is in the same phase will be added and if it is out of phase, will be canceled. The designs have been investigated at different bit-rates to achieve higher extinction ratio (ER), Q-factor and bit-error rate (BER) for different pump currents of SOA.     

Design and performance analysis in multiuser optical CDMA systems

The article presents comparative performance analysis of the proposed Optical CDMA system for 32 and 16 users with two dimensional codes. Numerical simulations have been done under interference significant environment, considering noise and dark current at data rates 2.5, 5, 7.5 and 10 Gbps over single mode fiber for transmission distance of more than 270 km. Results illustrate overall good performance, degraded with augment in bit rate and transmission distance, impervious with raise in number of simultaneous active users. Depicts significant performance improvement with inclusion of forward error correction RS (255,239), for low attenuation and chirp factor. It perceived, this is one of the efficient functional techniques for next generation broadband optical networks together with higher security owing to encoding and decoding, as it allow multiple users in the network to access the same fiber channel asynchronously.     

Tuning electrochemical potential of LiCoO2 with cation substitution: first-principles predictions and electronic origin

With a goal to improve the performance of LiCoO₂ as a cathode material in Li-ion batteries, we simulate substitution of various elements (X = Be, Mg, Al, Ga, Si and Ti) for Co using first-principles density functional theory and predict changes in its electrochemical potential. While the electrochemical potential of LiCoO₂ is enhanced with substitution of Be, Mg, Al and Ga for Co, an opposite effect is predicted of Si and Ti substitution. We determine the electronic origin of these changes in electrochemical potential using (a) Bader method of topological analysis of charge density, (b) partial density of electronic states to estimate oxidation states of metal and oxygen, and charge re-distribution upon lithiation. We find that the distribution of electronic charge donated by Li is influenced by the nature of the X–O bond. A larger electron transfer to O (in XO₆ octahedron) upon lithiation leads to stronger Li intercalation and thereby higher electrochemical voltage. Our findings provide a platform for a rational design of cathode materials in Li batteries with enhanced voltage.     

Droplet shape analysis and permeability studies in droplet lipid bilayers

We apply optical manipulation to prepare lipid bilayers between pairs of water droplets immersed in an oil matrix. These droplet pairs have a well-defined geometry allowing the use of droplet shape analysis to perform quantitative studies of the dynamics during bilayer formation and to determine time-dependent values for the droplet volumes, bilayer radius, bilayer contact angle, and droplet center-line approach velocity. During bilayer formation, the contact angle rises steadily to an equilibrium value determined by the bilayer adhesion energy. When there is a salt concentration imbalance between droplets, there is a measurable change in the droplet volume. We present an analytical expression for this volume change and use this expression to calculate the bilayer permeability to water.