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.     

Aqueous extracts of Agave sisalana boles have prebiotic potential

Abstract

This work aimed at evaluating the prebiotic potential of the aqueous extract and crude polysaccharides from Agave sisalana boles by an in vitro screening. Crude polysaccharides were obtained from the aqueous bole extract by precipitation with acetone and resuspension in water. The liquid extract and the polysaccharide solution were then spray dried and submitted to thermal analysis and quantification of metabolites. Prebiotic activity was checked on probiotic strains belonging to the Lactobacillus genus using inulin, fructo-oligosaccharides, fructose and glucose as positive controls. The powder of A. sisalana bole extract, which has recently been identified as a rich source of inulin, exhibited higher potential of fermentation compared with crude polysaccharides.     

Development of a capillary electrophoresis method for the enantioselective estimation of primaquine in pharmaceutical formulations

A capillary electrophoresis (CE) method has been developed that allows the separation and estimation of primaquine enantiomers using hydroxypropyl-gamma-cyclodextrin (HP-gamma -CD) as a chiral selector. The influence of chemical and instrumental parameters on the separation, such as type and concentration of CD, buffer concentration, buffer pH, applied voltage, capillary temperature, and injection time, were investigated. Good separation of the racemic mixture of primaquine was achieved using a fused-silica capillary (52.5 cm effective length x 50 microm id) and a background electrolyte composed of tris-phosphate buffer solution (50 mM, pH 2.5) containing 15 mM HP-gamma-CD as a chiral selector. The recommended applied voltage, capillary temperature, and injection time were 15 kV, 25 degrees C, and 6 s, respectively. Within-day and interday reproducibility of peak area and migration time gave relative standard deviation values ranging from 1.05-3.30%. Good recoveries (range of 96.8-104.9%) were obtained from the determination of placebos that were spiked with 0.25-1.00 mg/L primaquine. The proposed CE method was successfully applied to the assay of primaquine diphosphate in pharmaceutical formulations (tablets).     

Turbo charging time-dependent density-functional theory with Lanczos chains

We introduce a new implementation of time-dependent density-functional theory which allows the entire spectrum of a molecule or extended system to be computed with a numerical effort comparable to that of a single standard ground-state calculation. This method is particularly well suited for large systems and/or large basis sets, such as plane waves or real-space grids. By using a superoperator formulation of linearized time-dependent density-functional theory, we first represent the dynamical polarizability of an interacting-electron system as an off-diagonal matrix element of the resolvent of the Liouvillian superoperator. One-electron operators and density matrices are treated using a representation borrowed from time-independent density-functional perturbation theory, which permits us to avoid the calculation of unoccupied Kohn-Sham orbitals. The resolvent of the Liouvillian is evaluated through a newly developed algorithm based on the nonsymmetric Lanczos method. Each step of the Lanczos recursion essentially requires twice as many operations as a single step of the iterative diagonalization of the unperturbed Kohn-Sham Hamiltonian. Suitable extrapolation of the Lanczos coefficients allows for a dramatic reduction of the number of Lanczos steps necessary to obtain well converged spectra, bringing such number down to hundreds (or a few thousands, at worst) in typical plane-wave pseudopotential applications. The resulting numerical workload is only a few times larger than that needed by a ground-state Kohn-Sham calculation for a same system. Our method is demonstrated with the calculation of the spectra of benzene, C(60) fullerene, and of chlorophyll a.     

Stepwise optimization and sensitivity improvement of green micellar electrokinetic chromatography method to simultaneously determine some fluoroquinolones and glucocorticoids present in various binary ophthalmic formulations

A sensitive micellar electrokinetic chromatography method is presented to simultaneously quantify ofloxacin, gatifloxacin, dexamethasone sodium phosphate and prednisolone acetate. The method has the advantages of being rapid, accurate, reproducible, ecologically acceptable and sensitive. The electrophoretic separation utilized 20 mm borate buffer as background electrolyte with pH 10.0 ± 0.1 and 50 mm sodium dodecyl sulfate as a micelle forming molecule. A capillary tube (50 μm i.d., 33 cm) of fused silica was used and on-column diode array detection at 243 nm for dexamethasone sodium phosphate and prednisolone acetate, and 290 nm for ofloxacin and gatifloxacin. Various factors were optimized such as the background electrolyte (type, concentration and pH), addition of sodium dodecyl sulfate and its concentration, detection wavelength, applied voltage and injection parameters. The studied drugs were efficiently separated in 6.2 min, at 20 kV with high resolution. The greenness of the method was estimated using an eco-scale tool and the presented method was found to have excellent green characteristics. The method was validated in conformance with International Conference on Harmonization guidelines, with acceptable accuracy, precision and selectivity. The suggested method can be employed for the economic analysis of the four drugs in dissimilar binary combinations of eye drops saving solvents and chemicals.     

Volumes of activation for dissociation of pentacyanoferrates(II) through pressure and salt effects on reactivity

Summary Dependences of rate constants on pressure (up to 1 kbar) and on added salt concentration (up to 6.0 mol dm^–3 LiNO₃, NaNO₃, NaCl, Na₂SO₄ or KNO₃) have been established for dissociative substitution of pentacyanoferrates(II), [Fe(CN)₅L]^3– with L = 4-cyanopyridine, 4,4-bipyridyl, 4-phenylpyridine and 4-t-butylpyridine. Activation volumes derived directly from pressure effects, and indirectly from salt effects via surface tension dependences and derived surfaces of activation, are reported, compared and discussed.     

Formation of a Single-Crystal Aluminum-Based MOF Nanowire with Graphene Oxide Nanoscrolls as Structure-Directing Agents

An innovative strategy is proposed to synthesize single-crystal nanowires (NWs) of the Al³⁺ dicarboxylate MIL-69(Al) MOF by using graphene oxide nanoscrolls as structure-directing agents. MIL-69(Al) NWs with an average diameter of 70±20 nm and lengths up to 2 μm were found to preferentially grow along the [001] crystallographic direction. Advanced characterization methods (electron diffraction, TEM, STEM-HAADF, SEM, XPS) and molecular modeling revealed the mechanism of formation of MIL-69(Al) NWs involving size-confinement and templating effects. The formation of MIL-69(Al) seeds and the self-scroll of GO sheets followed by the anisotropic growth of MIL-69(Al) crystals are mediated by specific GO sheets/MOF interactions. This study delivers an unprecedented approach to control the design of 1D MOF nanostructures and superstructures.     

Extraction of biogenic amines using sorbent materials containing immobilized crown ethers

Three sorbent materials (A18C6-MS, DA18C6-MS and AB18C6-MS) based on the crown ether ligands, 1-aza-18-crown-6, 1,4,10,13-tetraoxa-7,16-diazacyclo octadecane and 4′-aminobenzo-18-crown-6, respectively, were prepared by the chemical immobilization of the ligand onto mesoporous silica support. The sorbents were characterized by FT-IR, scanning electron microscopy-energy dispersive X-ray microanalysis, elemental analysis and nitrogen adsorption-desorption test. The applicability of the sorbents for the extraction of biogenic amines by the batch sorption method was extensively studied and evaluated as a function of pH, biogenic amines concentration, contact time and reusability. Under the optimized conditions, all the sorbents exhibited highest selectivity toward spermidine (SPD) compared to other biogenic amines (tryptamine, putrescine, histamine and tyramine). Among the sorbents, AB18C6-MS offer the highest capacity and best selectivity towards SPD in the presence of other biogenic amines. The AB18C6-MS sorbent can be repeatedly used three times as there was no significant degradation in the extraction of the biogenic amines (%E > 85). The optimized procedure was successfully applied for the separation of SPD in food samples prior to the reversed-phase high performance liquid chromatography separation.     

Syntheses, crystal structures, transport properties and first-principles electronic structure study of the (tTTF)2X (X=Br, I) low-dimensional antiferromagnets

An efficient synthetic procedure for the preparation of unsymmetrically substituted tetrathiafulvalene (TTF) donors has been used to obtain the trimethylene-tetrathiafulvalene (tTTF) donor with high purity. Good quality crystals of the two (tTTF)(2)X (X = Br, I) salts have been obtained by electrocrystallization. The two salts are isomorphous and contain tTTF layers which are built from (tTTF)(2) dimeric units. Both systems are low-dimensional antiferromagnets with the highest Ne?el temperatures for TTF based radical cation salts: ≈ 35 K (Br salt) and ≈43 K (I salt). The resistivity is found to substantially decrease with pressure although both salts still have activated conductivity at 25 kbar. First-principles Density Functional Theory (DFT) calculations have been used to investigate the relative strength of the three different types of magnetic interactions in the tTTF layers as well as the potential magnetic ground states. These calculations successfully predict the nature of the ground state and suggest a possible correlation between structural details and Ne?el temperatures for the bromine and iodine salts. Remarkably, the calculated antiferromagnetic ground state can be predicted from the nesting properties of the Fermi surface for the hypothetical Pauli paramagnetic metallic state.     

Hydrazone-based ligands for micro-solid phase extraction-high performance liquid chromatographic determination of biogenic amines in orange juice

Eight hydrazone-based ligands were synthesized, trapped in a silica sol-gel matrix, and were subsequently used in the micro-solid phase extraction (μ-SPE) of biogenic amines (BAs). The BAs investigated were tryptamine, phenylethylamine, putrescine, histamine, tyramine and spermidine. Prior to the extraction, dansyl chloride was added to the samples which were heated to 70°C for 10 min. The samples were extracted with μ-SPE, after which analytes were desorbed using acetonitrile via ultrasonication. The extracts were analysed by high performance liquid chromatography (HPLC) with ultraviolet detection. Of the eight ligands investigated as sorbents, benzophenone 2,4-dinitrophenylhydrazone was found to be the most promising. The enhanced π-π interaction between the analytes and the ligand facilitated the adsorption process. Under the most suitable extraction conditions, the method demonstrated good linearity with correlation coefficient of more than 0.985 over a concentration range of 1-50 μg L(-1). Satisfactory repeatability with relative standard deviations of 7.43-11.30% (n=3) were obtained. Detection limits ranged from 3.8 to 31.3 ng L(-1). The μ-SPE method exhibited lower recoveries (71.5-87.4%) when compared to the solid phase extraction technique (79.7-95.0%), but enrichment factors of 94-460 were obtained. The proposed μ-SPE-HPLC method was applied to the determination of BAs in orange juice purchased from local supermarkets, with satisfactory results. The orange juices were characterized by the presence of relatively high levels of putrescine (range, 550-2210 μg L(-1)) but tryptamine and phenylethylamine were not detected in any of the tested samples.