A review of bioanalytical methods for chronic lymphocytic leukemia drugs and metabolites in biological matrices

Quantitation of drugs used for the treatment of chronic lymphocytic leukemia in various biological matrices during both pre-clinical and clinical developments is very important, often in routine therapeutic drug monitoring. The first developed methods for quantitation were traditionally done on LC in combination with either UV or fluorescence detection. However, the emergence of LC with mass spectrometry in tandem in early 1990s has revolutionized the quantitation as it has provided better sensitivity and selectivity within a shorter run time; therefore it has become the choice of method for the analysis of various drugs. In this article, an overview of various bioanalytical methods (HPLC or LC–MS/MS) for the quantification of drugs for the treatment of chronic lymphocytic leukemia, along with applicability of these methods, is given.     

Simultaneous determination of colchicine and febuxostat in rat plasma: Application in a rat pharmacokinetic study

A selective, sensitive and rapid LC–MS/MS method has been developed and validated as per US Food and Drug Administration regulatory guidelines for the simultaneous quantitation of colchicine and febuxostat in rat plasma. Colchicine and febuxostat were extracted from the rat plasma using 10% tert-butyl methyl ether in ethyl acetate using colchicine-d₆ as an internal standard (IS). The chromatographic separation of colchicine, febuxostat and the IS was achieved using a mobile phase comprising 5 mm ammonium formate and 0.025% formic acid in acetonitrile (20:80, v/v) in isocratic mode on an Eclipse XDB-C₁₈ column. The injection volume and flow rate were 5.0 μl and 0.9 ml/min, respectively. Colchicine and febuxostat were detected by positive electrospray ionization in multiple reaction monitoring mode using transition pairs (Q1 → Q3) of m/z 400.10 → 358.10 and 317.05 → 261.00, respectively. The assay was linear in the ranges of 0.25–254 and 2.60–622 ng/ml for colchicine and febuxostat, respectively. The inter- and intra-day precision values were 0.58–13.0 and 1.03–4.88% for colchicine and febuxostat, respectively. No matrix or carryover effects were observed during the validation. Both analytes were stable on the bench-top, in the autosampler and in storage (freeze–thaw cycles and long-term storage at −80 ° C). A pharmacokinetic study in rats was performed to show the applicability of the validated method.     

Positive Solutions to Singular Boundary Value Problems with Sign Changing Nonlinearities on the Half-Line via Upper and Lower Solutions

This paper presents a lower and upper solution technique for singular second order boundary value problems on the half line.     

Surface studies on bimetallic thiocyanate ligand based single crystals of MnHg(SCN)4, CdHg(SCN)4 and ZnCd(SCN)4

Bimetallic SCN ligand based single crystals of manganese mercury thiocyanate (MMTC), cadmium mercury thiocyanate (CMTC) and zinc cadmium thiocyanate (ZCTC) are grown by slow solvent evaporation technique. The growth mechanism and surface features are investigated by optical microscopic techniques such as scanning electron microscopy (SEM) and atomic force microscopy (AFM). The laser induced surface damage measurements were carried out using a Q-switched Nd:YAG laser at 1064 nm with laser beam of 1.0 Hz and pulse duration 25 ps. The laser damage threshold values of MMTC, CMTC and ZCTC are found to be 15.9, 22.9 and 19.7 GW/cm², respectively. The SEM analysis of MMTC reveals the formation of elongated dendrite growth pattern caused by the fluctuations of Mn and Hg metal ligands when thiocyanate (SCN) bridges them. The etching study indicates the occurrence of different types of etch pit patterns like terraced triangles, pillars, pyramids and rods. The AFM images confirm the formation of three major hillocks with cavities in MMTC. The measured roughness values for CMTC crystal are very much lower than that of MMTC.     

Ply-by-Ply Failure Analysis of Laminates Under Dynamic Loading

Ply-by-ply failure analysis of symmetric and anti-symmetric laminates under uniform sinusoidal transverse dynamic loading is performed for a specified duration. The study investigates the first ply failure load, followed by the detection of successive ply failures along with their failure modes using various failure theories. Some of the well-established failure theories, mostly used by the researchers, are considered for the failure prediction in laminates. The finite element computational model based on higher order shear deformation displacement field is used for the failure analysis and the complete methodology is computer coded using FORTRAN. The ply-discount stiffness reduction scheme is employed to modify the material properties of the failed lamina. The failure theories used in the analysis are compared according to their ability to predict failure load, failed ply, failure mode and progression of failure. The failure analysis is performed for both the cross-ply and angle-ply laminates with all edges simply supported and clamped. The significance of fibre orientation and stacking sequence in terms of the strength of a laminate and failure progression is also highlighted.     

On pathwise behavior of multiserver queues

In this paper, by exploiting recent results on the pathwise behavior of the workload process in single server, work conserving queues of theG/G/1/ type, we show that the workload of multiserver, work conserving queues ofG/G/m/ (m<) (andG/G/) queues satisfies an o(t) growth condition, provided that the time average of the work brought into the system is less thanm form < (and finite form=).     

Theoretical studies on the structure,sensitivity, density,thermodynamic properties and detonation performance of dinitrobitriazoles

Azodinitro- and dinitroethylene-bridged bitriazoles are of interest in the contest of high explosives, and were found to have true local energy minima at the B3LYP/aug-cc-pVDZ level of theory. The optimised structures, vibrational frequencies and thermodynamic quantities for bitriazoles were obtained in the ground state. Kamlet–Jacobs equations were used to evaluate the performance of bitriazoles based on the predicted density and the calculated heat of explosion. Detonation properties (D = 8.12 to 9.23 km s^?1 and P = 28.0 to 39.83 GPa) of bitriazoles were found to be promising compared with those of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX, D = 8.75 km s^?1 and P = 34.7 GPa) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX, D = 8.96 km s^?1 and P = 35.96 GPa). The fusion of azoles particularly appears to be a promising area for investigation, since it may lead to the desirable consequences of higher heat of explosion, higher density and thus improved detonation performance.     

Spectral features of laser induced plasma from YBa2Cu3O7 and GdBa2Cu3O7 highT c superconductors

Laser induced plasma emission spectra from highT _c superconducting samples of YBa₂Cu₃O₇ and GdBa₂Cu₃O₇ obtained with 1.06μm radiation from a Q switched Nd:YAG laser beam has been analysed. The results clearly show the presence of diatomic oxides in addition to ionized species of the constituent metals in the plasma thus produced.     

Behavior of nonlinear fluid viscous dampers for control of shock vibrations

Fluid viscous dampers have been widely used for suppression of high velocity shocks. While linear fluid viscous dampers have been used for a long time, nonlinear fluid viscous dampers show considerable promise due to their superior energy dissipation characteristics and significant reduction in the damper force compared to a linear fluid viscous damper for the same peak displacement. This paper presents results from experimental study to characterize fluid viscous dampers when subjected to half-cycle sine shock excitation. The mathematical formulation and a numerical study to evaluate the relative performance of structures with fluid viscous dampers subjected to short-duration shock (impulse) loading are also discussed. The influence of damper nonlinearity (α) and the supplemental damping ratio (ξ_sd) on response has been investigated. The supplemental damping ratio of nonlinear fluid viscous dampers when subjected to shock excitation is found by equivalent linearization using the concept of equal energy dissipation. The paper also presents some design charts, which can be used for preliminary decisions on parameters of nonlinear dampers to be used in design.