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.     

Efficient eco-friendly syntheses of dithiocarbazates and thiosemicarbazones

ABSTRACT

Eight Schiff bases have been synthesized by conventional and three different eco-friendly methods, whereby two aromatic carbonyl compounds viz. 2-thiophenecarboxaldehyde and salicylaldehyde were reacted with S-methyl, S-benzyl, and S-n-octyl-dithiocarbazates and thiosemicarbazide. In order to evaluate the efficiency of the synthesis methods, the time to complete the reaction and the yield of the Schiff base synthezised by eco-friendly methods, such as solvent-free grinding, water as a solvent, and lemon juice as catalyst, were compared with those synthesized by the conventional method. The chemical structures of all the synthesized Schiff bases, where two of them are novel and reported for the first time, were fully characterized by a variety of physico-chemical, analytical, and spectroscopic techniques. The molecular and crystal structures of the Schiff bases especially those having 2-thiophene moiety were further elucidated by single crystal X-ray diffraction analyzes.     

Fluid Flow Analysis of Integrated Porous Bone Scaffold and Cancellous Bone at Different Skeletal Sites: In Silico Study

The dynamic characteristic of bone is its ability to remodel itself through mechanobiological responses. Bone regeneration is triggered by mechanical cues from physiological activities that generate structural strain and cause bone marrow movement. This phenomenon is crucial for bone scaffold when implanted in the cancellous bone as host tissue. Often, the fluid movement of bone scaffold and cancellous bone is studied separately, which does not represent the actual environment once implanted. In the present study, the fluid flow analysis properties of bone scaffold integrated into the cancellous bone at different skeletal sites are investigated. Three types of porous bone scaffolds categorized based on pore size configurations: 1 mm, 0.8 mm and hybrid (0.8 mm interlaced with 0.5 mm) were used. Three different skeletal sites of femoral bone were selected: neck, lateral condyle and medial condyle. Computational fluid dynamics was utilized to analyze the fluid flow properties of bone scaffold integrated cancellous bone. The results of this study reveal that the localization and maximum value of shear stress in an independent bone scaffold are significantly different compared to the bone scaffold integrated with cancellous bone by about 160% to 448% percentage difference. Low shear stress and high permeability were found across models that have higher Tb.Sp (trabecular separation). Specimen C and femoral lateral condyle showed the highest permeability in their respective category.

     

Dielectric Properties of Colossal-Dielectric-Constant Na1/2La1/2Cu3Ti4O12 Ceramics Prepared by Spark Plasma Sintering

In the current study, we report on the dielectric behavior of colossal-dielectric-constant Na_1/2La_1/2Cu₃Ti₄O₁₂ (NLCTO) ceramics prepared by mechanochemical synthesis and spark plasma sintering (SPS) at 850 °C, 900 °C, and 925 °C for 10 min. X-ray powder diffraction analysis showed that all the ceramics have a cubic phase. Scanning electron microscope observations revealed an increase in the average grain size from 175 to 300 nm with an increase in the sintering temperature. SPS NLCTO ceramics showed a room-temperature colossal dielectric constant (>10³) and a comparatively high dielectric loss (>0.1) over most of the studied frequency range (1 Hz–40 MHz). Two relaxation peaks were observed in the spectra of the electrical modulus and attributed to the response of grain and grain boundary. According to the Nyquist plots of complex impedance, the SPS NLCTO ceramics have semiconductor grains surrounded by electrically resistive grain boundaries. The colossal dielectric constant of SPS NLCTO ceramics was attributed to the internal barrier layer capacitance (IBLC) effect. The high dielectric loss is thought to be due to the low resistivity of the grain boundary of SPS NLCTO.     

Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases

Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs.     

Determination of the effective atomic and mass numbers for mixture and compound materials in high energy photon interactions

In consideration the radiological properties of materials and studying the scattering processes in atomic and nuclear physics, the effective atomic and mass numbers is widely employed. These numbers have been calculated for any mixed or composite materials in interaction with high energy photons (Linac in radiation therapy). A pair equation in terms of these numbers is obtained. The first equation has been derived from the conservation of mass energy law and the second by minimizing the binding energy from the semiempirical mass formula (Myers and Swiatecki formula) that gives a relation between atomic and mass numbers for stable nuclei approximately. By these equations one can obtain the effective atomic and mass numbers for any compound or mixed materials uniquely. These numbers are calculated for some materials and compared with the other studies.     

Effect of styrene–acrylonitrile content on 0.5?M NaI/0.05?M I2 liquid electrolyte encapsulation for dye-sensitized solar cells

The effect of a gel polymer electrolyte (GPE) as the redox electrolyte used in dye-sensitized solar cells was studied. A GPE solution consisting of 0.5?M sodium iodide, 0.05?M iodine, and ethylene carbonate/propylene carbonate (1:1 w/w) binary solvents was mixed with increasing amounts of styrene–acrylonitrile (SAN). Bulk conductivity measurements show a decreasing trend from 4.54 to 0.83×10^?3?S?cm^?1 with increasing SAN content. The GPE exhibits Newtonian-like behavior and its viscosity increases from 0.041 to 1.093?Pa?s with increasing SAN content. A balance between conductivity (1.3?×?10^?3?S?cm^?1) and viscosity (1.4?Pa?s) is observed at 19?wt.% SAN. Fourier transform infrared spectroscopy detects elevated ring torsion at 706?cm^?1 upon the addition of SAN into the liquid electrolyte. This indicates that SAN does not bond with the liquid electrolyte. Finally, the potential stability window of 19?wt.% SAN, which ranges from ?1.68 to 1.38?V, proves its applicability in solar cells.     

Malayanines A and B, two novel limonoids from Chisocheton erythrocarpus Hiern

Two structurally interesting novel limonoids, malayanine A and malayanine B, were isolated from the bark of Chisocheton erythrocarpus Hiern. The structures were fully characterized through spectroscopic methods.