Determination of quinocide as impurity in primaquine tablets by capillary zone electrophoresis

A capillary zone electrophoretic method has been developed and validated for the determination of the impurity quinocide (QC) in the antimalarial drug primaquine (PQ). Different buffer additives such as native cyclodextrins and crown ethers were evaluated. Promising results were obtained when either β‐cyclodextrin (β‐CD) or 18‐crown‐6 ether (18C6) were used. Their separation conditions such as type of buffer and its pH, buffer additive concentration, applied voltage capillary temperature and injection time were optimized. The use of 18C6 offers slight advantages over β‐CD such as faster elution times and improved resolution. Nevertheless, migration times of less than 5 min and resolution factors (R_s) in the range of 2–4 were obtained when both additives were used. The method was validated with respect to selectivity, linearity, limits of detection and quantitation, analytical precision (intra‐ and inter‐day variability) and repeatability. Concentrations of 2.12 and 2.71% (w/w) of QC were found in pharmaceutical preparations of PQ from two different manufacturers. A possible mechanism for the successful separation of the isomers is also discussed. Copyright © 2008 John Wiley & Sons, Ltd.     

A novel synthesis of 2-arylhydrazono-6-amino-4-arylbenzene-1,3-dicarbonitriles and their conversion into phthalazines

Compounds 1a-d react with benzylidenemalononitrile 2 to yield dihydroaminopyridazines 3a-d and, in contrast, compounds 1e,f react with 2 under the same conditions to yield aminobenzenedicarbonitriles 8e,f compound 8e underwent intramolecular cyclization to phthalazine 9e. Compound 10e reacted with 2a to yield 11e.     

Quantum mechanical studies of the protonation and NBr bond dissociation of the biologically important N-bromosuccinimide

N-Bromosuccinimide (NBS) is a brominating and oxidizing agent that is used as a source of bromine. The proton affinities, the tautomeric forms and NBr bond dissociation of NBS have been computed using the B3LYP functional as implemented in the density functional approach. The electronic structures of all possible tautomeric forms of NBS have been thoroughly investigated. The keto form of NBS has been shown to be more stable than any other tautomeric forms. The geometries and relative energies for various stationary structures were determined. The results indicate clearly that O-site protonation is strongly favored over N-site protonation for the studied compound in case of mono- and di-protonation. The bond dissociation energies (BDEs), involving the formation of the bromine radical, cation, and anion, of the NBr bond have been investigated. The NBr BDE of the Br radical formation is lower than that of the Br anion or cation. These conclusions are in good agreement with the experimental results.     

Kinetic spectrophotometric determination of amodiaquine and chloroquine

Abstract  

Two simple, sensitive, and selective spectrophotometric methods were developed for determining amodiaquine (AQ) and chloroquine (CQ) based on their oxidation with potassium iodate and potassium bromate, respectively. The initial rates of oxidation of AQ and CQ were monitored at 342 and 343 nm, the wavelengths of maximum absorptions of the two drugs. The various experimental parameters affecting oxidation reactions were thoroughly studied and optimized. Beer’s law was obeyed for 0.2–4.0 and 0.5–5.0 μg cm⁻³, with correlation coefficients of 0.9999 and 0.9998 (n = 6) and a detection limit (based on the 3S _b -criterion) of 0.04 and 0.06 μg cm⁻³ for AQ and CQ. The proposed methods were conveniently applied to determining AQ and CQ in pure and dosage forms.     

Counter-flow electrokinetic supercharging for the determination of non-steroidal anti-inflammatory drugs in water samples

Electrokinetic supercharging (EKS) has been used in the last few years as a powerful tool for separation and on-line preconcentration of different types of analytes. We have developed a valuable modification for EKS system, namely counter-flow EKS (CF-EKS) and applied it for the separation and on-line preconcentration of seven non-steroidal anti-inflammatory drugs (NSAIDs) in water samples. In CF-EKS, a hydrodynamic counter-flow is applied during electrokinetic injection of the analytes within the EKS system. This counter-flow minimises the introduction of the sample matrix into the capillary, allowing longer injections to be performed. Careful choice of the optimum counter-flow as well as the optimum injection voltage allowed the sensitivity to be enhanced by 11,800-fold, giving limits of detection (LODs) of 10.7–47.0 ng/L for the selected NSAIDs. The developed method was validated and then applied for the determination of the studied NSAIDs in drinking water as well as wastewater samples from Hobart city.     

Rheological investigation of thermal transitions in vesicular dispersion

The thermal behavior of unsonicated dispersions of a double-chained surfactant, Dioctadecyldimethylammonium bromide (DODAB), has been studied over a wide concentration range using DSC and dynamic rheology. All dispersions are characterized by the pre- and main transition peaks at 35 °C and 43 °C, respectively. But, only above 10 mM DODAB, a third endotherm at 52 °C appears which may correspond to the (ULVs + L_α fragments) → MLVs transition. The thermal-induced MLV’s size is proportionally dependent on the concentration. In addition, and in agreement with DSC data, dynamic rheology has proven to be an indirect way to elucidate the structural transitions in these DODAB vesicular dispersions.     

Interaction of biological buffers with electrolytes: Densities of aqueous solutions of two substituted aminosulfonic acids and ionic salts from T = (298.15 to 328.15) K

Biological buffers are of utmost importance for research in biological and clinical chemistry and in oceanography, but they may not be inert enough, thus interfering with the system under study. The N-[Tris(hydroxymethyl)methyl]-3-aminopropanesulfonic acid (TAPS) and N-[Tris(hydroxymethyl)methyl]-3-amino-2-hydroxypropanesulfonic acid (TAPSO) are useful zwitterionic buffers for pH control as standard buffers in the physiological region of pH 7.7 to 9.1 for TAPS and 7.0 to 8.2 for TAPSO, respectively. In this work, interaction between these zwitterionic compounds and electrolytes of potassium acetate (KAc), potassium bromide (KBr), potassium chloride (KCl), and sodium chloride (NaCl) were investigated through measuring the densities of these buffers in aqueous and in aqueous electrolyte solutions by a high precision vibrating tube digital densitometer from T = (298.15 to 328.15) K under atmospheric pressure. In this series of measurements, the aqueous samples were prepared with various concentrations of the zwitterionic buffers, up to saturated conditions, and over salt concentrations from (1 to 4) mol · dm^?3. The measured densities served to evaluate the cubic expansion coefficients, α(m, T) and the apparent molar volumes, V_?(m, T). An empirical equation was used to correlate quantitatively the experimental densities over the entire concentration ranges.     

Photoinduced processes of newly synthesized bisferrocene- and bisfullerene-substituted tetrads with a triphenylamine central block

Photoinduced electron transfer processes of two newly synthesized tetrads with a triphenylamine (TPA) as central building block, to which bisfullerenes (C₆₀) and bisferrocenes (Fc) are covalently connected, have been studied. One of them has a TPA linked with one C₆₀ moiety and two ferrocene moieties C₆₀-TPA-(Fc)₂ and another tetrad has a TPA linked with two C₆₀ moieties and one ferrocene unit (C₆₀)₂-TPA-Fc. The photophysical properties of (C₆₀)_m-TPA-(Fc)_n have been investigated by applying the picosecond time-resolved fluorescence and nanosecond transient absorption techniques in both polar and nonpolar solvents. The charge separation process via the excited singlet state of the C₆₀ moiety of the C₆₀-TPA-(Fc)₂ is more efficient than that of the (C₆₀)₂-TPA-Fc. It is found that the ratio of Fc-donor to C₆₀-acceptor affects charge separation efficiency via the excited singlet state of the C₆₀ moiety.     

Development and Validation of HPLC,TLC and Derivative Spectrophotometric Methods for the Analysis of Ezetimibe in the Presence of Alkaline Induced Degradation Products

Reversed phase‐high performance liquid chromatography (RP‐HPLC), thin layer chromatography (TLC) densitometry and first derivative spectrophotometry (1D) techniques are developed and validated as a stability‐indicating assay of ezetimibe in the presence of alkaline induced degradation products. RP‐HPLC method involves an isocratic elution on a Phenomenex Luna 5μ C₁₈ column using acetonitrile: water: glacial acetic acid (50:50:0.1 v/v/v) as a mobile phase at a flow rate of 1.5 mL/min. and a UV detector at 235 nm. TLC densitometric method is based on the difference in Rf‐values between the intact drug and its degradation products on aluminum‐packed silica gel 60 F₂₅₄ TLC plates as stationary phase with isopropanol: ammonia 33% (9:1 v/v) as a developing mobile phase. On the fluorescent plates, the spots were located by fluorescence quenching and the densitometric analysis was carried out at 250 nm. Derivative spectrophotometry, the zero‐crossing method, ezetimibe was determined using first derivative at 261 nm in the presence of its degradation products. Calibration graphs of the three suggested methods are linear in the concentration ranges 1–10 mcg/mL, 0.1–1 mg/mL and 1–16 mcg/mL with a mean percentage accuracy of 99.05 ± 0.54%, 99.46 ± 0.63% and 99.24 ± 0.82% of bulk powder, respectively. The three proposed methods were successfully applied for the determination of ezetimibe in raw material and pharmaceutical dosage form; the results were statistically analyzed and compared with those obtained by the reported method. Validation parameters were determined for linearity, accuracy and precision; selectivity and robustness and were assessed by applying the standard addition technique.     

Isolation of tumor cells using size and deformation

The isolation and analysis of circulating tumor cells (CTCs) from blood are the subject of intense research. Although tests to detect metastasis on a molecular level are available, progress has been hampered by a lack of tumor-specific markers and predictable DNA abnormalities. The main challenge in this endeavor is the small number of available cells of interest, 1–2 per mL in whole blood. We have designed a micromachined device to fractionate whole blood using physical means to enrich for and/or isolate rare cells from peripheral circulation. It has arrays of four successively narrower channels, each consisting of a two-dimensional array of columns. Current devices have channels ranging in width from 20 to 5 μm, and in depth from 20 to 5 μm. Several optimizations resulting in the fabrication of a total of 10 derivative devices have been carried out; only two types are used in this study. Both have increasingly narrower gap widths between the columns along the flow axis with 20, 15, 10, and 5 μm spacing all on one device. The first 20 μm wide segment disperses the cell suspension and creates an evenly distributed flow over the entire device, whereas the others were designed to retain increasingly smaller cells. The channel depth is constant across the entire device, the first type was 10 μm deep and the second type is 20 μm deep. When cells from each of eight tumor cell lines were loaded into the device, all cancerous cells were isolated. In mixing experiments using human whole blood, we were able to fractionate cancer cells without interference from the blood cells. Additionally, either intact cells, or DNA, could be extracted for molecular analysis. The ultimate goal of this work is to characterize the cells on the molecular level to provide non-invasive methods to monitor patients, stage disease, and assess treatment efficacy. Furthermore, this work will use gene expression profiles to gain insights into metastasis.