Analytical method development and validation of anticancer agent, 5-fluorouracil,and its metabolites in biological matrices: An updated review

Abstract

5-fluorouracil (5-FU) refers to a fluorinated pyrimidine analogue that has been widely used as an anticancer agent for colon, head, and neck cancers. Detection of 5-FU and its metabolites; 5-fluorouridine and 5-fluoro-2-deoxyuridine in biological samples allows optimization of pharmacotherapy and encourages fundamental investigations of this medication. The development of accurate and reliable sample preparation, as well as analytical methods, is critical to isolate targeted analytes from complex matrices, apart from increasing detection sensitivity of analytes. With that, this paper presents a review of prior studies pertaining to chromatographic and electrophoretic methods that focused on the analysis of 5-FU and its metabolites in biological matrices such as plasma and urine. This paper concentrates on HPLC, GC and CE systems, which are the most commonly used strategies for analytical separation of 5-FU and its metabolites from samples. Detection of these antineoplastic agents at trace level demands highly sensitive and selective analytical methodologies. Application of these analytical techniques to biological matrices is reviewed with a focus on method development strategies, including types of mobile phases and background electrolytes employed in LC and CE systems.     

Development and validation of HPLC method for simultaneous estimation of piperine and guggulsterones in compound Unani formulation (tablets) and a nanoreservoir system

An attempt has been made to develop and validate a simultaneous HPLC method for novel approach of drug release via oil‐in‐water (o/w) nanoemulsion formulation and Habb‐e‐Khardal Unani tablet containing piperine and guggul sterones E and Z as main ingredients. Nanoemulsion was prepared by titration method using sefsol‐218 as an oily phase, cremophor‐EL as a surfactant, transcutol as a co‐surfactant and distilled water as an aqueous phase. The formulation was optimized on the basis of thermodynamic stability and dispersibilty test. The nanoformulation was evaluated for particle size, surface morphology, electrical conductivity and viscosity determination. The in vitro dissolution was carried out by dialysis bag method. Drugs were quantified using an HPLC method developed in‐house with a C₁₈ column as stationary phase and acetonitrile and water as mobile phase at λ_max of 240 nm. The optimized formulation showed higher drug release, lower droplet size and less viscosity as compared with the conventional Habb‐e‐Khardal Unani tablet. The present study illustrated the potential of nanoemulsion dosage form in improving biopharmaceutic performance of piperine and guggul sterone. The HPLC method was also found to be quite sufficient for the routine quality control of formulations containing piperine and guggul sterone E and Z as ingredients and also for in vitro drug release studies. Copyright © 2011 John Wiley & Sons, Ltd.     

Plumbagin Alleviates Intracerebroventricular-Quinolinic Acid Induced Depression-like Behavior and Memory Deficits in Wistar Rats

Plumbagin, a hydroxy-1,4-naphthoquinone, confers neuroprotection via antioxidant and anti-inflammatory properties. The present study aimed to assess the effect of plumbagin on behavioral and memory deficits induced by intrahippocampal administration of Quinolinic acid (QA) in male Wistar rats and reveal the associated mechanisms. QA (300 nM/4 μL in Normal saline) was administered i.c.v. in the hippocampus. QA administration caused depression-like behavior (forced swim test and tail suspension tests), anxiety-like behavior (open field test and elevated plus maze), and elevated anhedonia behavior (sucrose preference test). Furthermore, oxidative–nitrosative stress (increased nitrite content and lipid peroxidation with reduction of GSH), inflammation (increased IL-1β), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were observed in the hippocampus region of QA-treated rats as compared to normal controls. Plumbagin (10 and 20 mg/kg; p.o.) treatment for 21 days significantly ameliorated behavioral and memory deficits in QA-administered rats. Moreover, plumbagin treatment restored the GSH level and reduced the MDA and nitrite level in the hippocampus. Furthermore, QA-induced cholinergic dysfunction and mitochondrial impairment were found to be ameliorated by plumbagin treatment. In conclusion, our results suggested that plumbagin offers a neuroprotective potential that could serve as a promising pharmacological approach to mitigate neurobehavioral changes associated with neurodegeneration.     

Study of isotope shifts,isotone shifts and nuclear compressibility from the analysis of muonic x-ray transitions

Muonic x-ray transitions in various spherical nuclei in the region 13?Z?83 have been analysed and the isotope and isotone shifts in charge radiusR are investigated. AssumingR=r ₀ A ^1/3, the isotopic and isotonic behaviour of the parameterr ₀ (=RA ^?1/3) is also studied. The variation ofr ₀ with mass numberA reveals the variation of average nucleon density, which in turn sheds light on the compressibility of nuclear matter. The isotope and isotone shifts inR exhibit the shell effects in the vicinity of magic neutron and proton numbers: 20, 28, 50, 82 and 126. The results indicate that neutron-proton interaction is maximum at the beginning of a major neutron shell and decreases gradually as the shell gets filled up. The behaviour of parameterr ₀ clearly suggests that low-Z nuclei are highly compressible while high-Z nuclei are more or less incompressible. The parameterr ₀ too is observed to exhibit profound shell effects.     

Lie-optics, geometrical phase and nonlinear dynamics of self-focusing and soliton evolution in a plasma

It is useful to state propagation laws for a self-focusing laser beam or a soliton in group-theoretical form to be called Lie-optical form for being able to predict self-focusing dynamics conveniently and amongst other things, the geometrical phase. It is shown that the propagation of the gaussian laser beam is governed by a rotation group in a non-absorbing medium and by the Lorentz group in an absorbing medium if the additional symmetry of paraxial propagation is imposed on the laser beam. This latter symmetry, however, needs care in its implementation because the electromagnetic wave of the laser sees a different refractive index profile than the laboratory observer in this approximation. It is explained how to estimate this non-Taylor paraxial power series approximation. The group theoretical laws so-stated are used to predict the geometrical or Berry phase of the laser beam by a technique developed by one of us elsewhere. The group-theoretical Lie-optic (or ABCD) laws are also useful in predicting the laser behavior in a more complex optical arrangement like in a laser cavity etc. The nonlinear dynamical consequences of these laws for long distance (or time) predictions are also dealt with. Ergodic dynamics of an ensemble of laser beams on the torus during absorptionless self-focusing is discussed in this context. From the point of view of new physics concepts, we introduce a stroboscopic invariant torus and a stroboscopic generating function in classical mechanics that is useful for long-distance predictions of absorptionless self-focusing.     

Fabrication and characterization of sputtered titanium dioxide films

TiO₂ thin films were prepared under various conditions by using a reactive RF sputtering technique. The structural, optical and electrical characteristics of the films have been investigated. All as-deposited films were amorphous. After annealing at T > 673 K, the crystallinity of the observed tetragonal anatase phase appeared improved. The optical band gap, determined by using Tauc plot, has been found to amount to 3.38 ± 0.03 and 3.21 ± 0.03 eV for the direct and indirect transition, respectively. Also the complex optical constants for the wavelength range 300-2500 nm are reported. Using the two-point probe technique, the dark resistivity has been measured as a function of the film thickness, d. The resistivity, ρ, of the samples has been found to decrease markedly with increasing thickness, but only for d < 100 nm. The behaviour of ρd versus d was found to fit properly with the Fuchs and Sondheimer relation with parameters ρ_o = 4.95 × 10⁶ Ω cm and mean free path, l = 310 ± 2 nm. The log ρ versus 1/T curves show three distinct regions with values for the activation energy of 0.03 ± 0.01, 0.17 ± 0.01 and 0.50 ± 0.02 eV, respectively.     

Band structures of symmetrical graphene superlattice with cells of three regions

We study the electronic band structures of massless Dirac fermions in symmetrical graphene superlattice with cells of three regions. opening gaps and additional Dirac points. Finally, we inspect the potential effect on minibands, the anisotropy of group velocity and the energy bands contours near Dirac points. We also discuss the evolution of gap edges and cutoff region near the vertical Dirac points.     

Bridging the Green Gap: Metal–Organic Framework Heteromultilayers Assembled from Porphyrinic Linkers Identified by Using Computational Screening

In organic photovoltaics, porphyrins (PPs) are among the most promising compounds owing to their large absorption cross-section, wide spectral range, and stability. Nevertheless, a precise adjustment of absorption band positions to reach a full coverage of the so-called green gap has not been achieved yet. We demonstrate that a tuning of the PP Q- and Soret bands can be carried out by using a computational approach for which substitution patterns are optimized in silico. The most promising candidate structures were then synthesized. The experimental UV/Vis data for the solvated compounds were in excellent agreement with the theoretical predictions. By attaching further functionalities, which allow the use of PP chromophores as linkers for the assembly of metal-organic frameworks (MOFs), we were able to exploit packing effects resulting in pronounced redshifts, which allowed further optimization of the photophysical properties of PP assemblies. Finally, we use a layer-by-layer method to assemble the PP linkers into surface-mounted MOFs (SURMOFs), thus obtaining high optical quality, homogeneous and crystalline multilayer films. Experimental results are in full accord with the calculations, demonstrating the huge potential of computational screening methods in tailoring MOF and SURMOF photophysical properties.