Integrated quality by design (QbD) and design of experiments (DoE) approach for UFLC determination of telaprevir in rat serum

An ultrafast liquid chromatographic bioanalytical method was developed and validated for the determination of telaprevir in Wistar albino rat serum. Principles of quality by design (QbD) were implemented for enhancing the bioanalytical liquid–liquid extraction of telaprevir from rat serum. A Box–Behnken design was utilized in the studies by selecting extraction time, centrifugation speed, and vortex time as the critical method variables for evaluating their effect on the critical analytical attribute, i.e., %recovery of telaprevir. Chromatographic separation was achieved within a run time of 10?min using a C-18 column and mobile phase comprising of methanol:borate buffer of pH 9 (90:10 v/v) flowing at 1.2?mL/min. Photodiode array detection was performed at 270?nm. Results of validation studies were satisfactory. The method was linear over a concentration of 25–10,000?ng/mL. Limit of detection for the developed method was 10?ng/mL. Further, design of experiments (DoE) used for inter-day accuracy and precision study suggested superior method reliability. This integrated QbD- and DoE-based approach ensured the development of a validated and reliable analytical method for optimum bioanalysis of telaprevir in biological matrix.     

Steric-effect induced alterations in streaming potential and energy transfer efficiency of non-newtonian fluids in narrow confinements

In this work, we explore the possibilities of utilizing the combined consequences of interfacial electrokinetics and rheology toward augmenting the energy transfer efficiencies in narrow fluidic confinements. In particular, we consider the exploitation of steric effects (i.e., effect of finite size of the ionic species) in non-Newtonian fluids over small scales, to report dramatic augmentations in the streaming potential, for shear-thickening fluids. We first derive an expression for the streaming potential considering strong electrical double layer interactions in the confined flow passage and the consequences of the finite conductance of the Stern layer, going beyond the Debye-Hu?ckel limit. With a detailed accounting for the excluded volume effects of the ionic species and their interaction with pertinent interfacial phenomena of special type of rheological fluids such as the power law fluids in the above-mentioned formalism, we demonstrate that a confluence of the steric interactions with the non-Newtonian transport characteristics may result in giant augmentations in the energy transfer efficiency for shear-thickening fluids under appropriate conditions.     

Examining the lateral displacement of HL60 cells rolling on asymmetric P-selectin patterns

The lateral displacement of cells orthogonal to a flow stream by rolling on asymmetrical receptor patterns presents a new opportunity for the label-free separation and analysis of cells. Understanding the nature of cell rolling trajectories on such substrates is necessary to the engineering of substrates and the design of devices for cell separation and analysis. Here, we investigate the statistical nature of cell rolling and the effect of pattern geometry and flow shear stress on cell rolling trajectories using micrometer-scale patterns of biomolecular receptors with well-defined edges. Leukemic myeloid HL60 cells expressing the PSGL-1 ligand were allowed to flow across a field of patterned lines fabricated using microcontact printing and functionalized with the P-selectin receptor, leveraging both the specific adhesion of this ligand-receptor pair and the asymmetry of the receptor pattern inclination angle with respect to the fluid shear flow direction (α = 5, 10, 15, and 20°). The effects of the fluid shear stress magnitude (τ = 0.5, 1, 1.5, and 2.0 dyn/cm(2)), α, and P-selectin incubation concentration were quantified in terms of the rolling velocity and edge tracking length. Rolling cells tracked along the inclined edges of the patterned lines before detaching and reattaching on another line. The detachment of rolling cells after tracking along the edge was consistent with a Poisson process of history-independent interactions. Increasing the edge inclination angle decreased the edge tracking length in an exponential manner, contrary to the shear stress magnitude and P-selectin incubation concentration, which did not have a significant effect. On the basis of these experimental data, we constructed an empirical model that predicted the occurrence of the maximum lateral displacement at an edge angle of 7.5°. We also used these findings to construct a Monte Carlo simulation for the prediction of rolling trajectories of HL60 cells on P-selectin-patterned substrates with a specified edge inclination angle. The prediction of lateral displacement in the range of 200 μm within a 1 cm separation length supports the feasibility of label-free cell separation via asymmetric receptor patterns in microfluidic devices.     

An efficient biomaterial supported bifunctional organocatalyst (ES-SO3- C5H5NH+) for the synthesis of β-amino carbonyls

A biomaterial supported organocatalyst, readily synthesized by the reaction of chemically modified sulfonic group containing expanded corn starch with pyridine exhibited excellent catalytic activity for the synthesis of β-amino carbonyls in excellent yields via aza-Michael addition of amines to electron deficient alkenes. A remarkable enhancement in the reaction rates was observed with the prepared bifunctional organocatalyst in comparison to the either starch grafted sulfonic acid or the corresponding homogeneous pyridinium p-toluenesulfonate.     

Synthesis of novel quinoline analogues of nimesulide: An unusual observation

Reduction of nimesulide followed by treating the N‐acyl derivative of resulting arylamine with Vilsmeier‐Haack reagent provided novel 2‐chloro‐3‐formylquinoline derivatives. The construction of quinoline ring using Vilsmeier‐Haack reagent afforded an unexpected compound, N‐(2‐chloro‐3‐formyl‐7‐phenoxy quinolin‐6‐yl)formamide, in addition to the expected product. The structure of this unexpected quinoline derivative was established via single‐crystal X‐ray analysis and its formation could be explained by an unprecedented N‐S bond cleavage under Vilsmeier‐Haack reaction conditions. The 2‐chloro‐3‐formylquinoline derivatives obtained were converted to a number of corresponding Schiff bases with potential pharmacological importance. J. Heterocyclic Chem., 2011.     

Molecular-shape selectivity by molecular gel-forming compounds: bioactive and shape-constrained isomers through the integration and orientation of weak interaction sites

A molecular gel system was assembled on carrier particles and the integrated effect of weak interaction sites enabled highly efficient separation of the bioactive and shape-constrained isomers of tocopherols, β-carotene, and polycyclic aromatic hydrocarbons (PAHs) by multiple interaction mechanisms.     

Baryogenesis at the electroweak scale

The generation of the baryon asymmetry of the universe is considered in the standard model of the electroweak theory with simple extensions of the Higgs sector. The propagation of quarks of masses up to about 5 GeV are considered, taking into account their markedly different dispersion relations due to propagation through the hot electroweak plasma. It is shown that the contribution of the b quark to the baryon asymmetry can be comparable to that for the t quark considered earlier.     

Photoinduced switch of a DNA/RNA inactive molecule into a classical intercalator

Spectroscopic titrations and thermal denaturation experiments show that "acyclic" analogue 1 does not bind to ds-DNA, but under same conditions "cyclic" 2 strongly interacts with ds-DNA and ds-RNA by intercalation into the double helix. Besides, 2 is significantly more effective in inhibition of the tumor cell growth in vitro than 1. We have shown that it is possible to efficiently and irreversibly convert "DNA inactive" compound 1 into "DNA active" compound 2 by light irradiation of the aqueous solutions of the former. This strategy offers a new and attractive approach to photoinduced anticancer therapy.