Band 64, Heft 3

The LBOZ criterion is an interesting approach for quantifying selectivity during spectrophotometric analysis by measuring the relative uncertainty increase caused by spectral overlapping. Unfortunately, no reference values for pharmaceuticals analysis in the UV region exist. The current paper presents an estimation of the LBOZ distribution as a random variable for binary and ternary drug mixtures. The estimation was done on a representative group of 170 diverse drug-like compounds. Results of the estimation were fitted to the beta and the Johnson distributions. The obtained parameters can be used to examine the “significance” of the spectral overlap by finding the p-value, interpreted as a chance to obtain higher uncertainty increase among the drugs.

Simple and rapid spectrophotometric methods have been developed for the microdetermination of fluoxetine HCl. The proposed methods are based on the formation of ion-pair complexes between fluoxetine and bromophenol blue (BPB), bromothymol blue (BTB), bromocresol green (BCG), and bromocresol purple (BCP) which can be measured at optimum λmax. Optimization of reaction conditions was investigated. Beerșs law was obeyed in the concentration ranges of 0.5–8.0 μg mL−1, whereas optimum concentration as adopted from the Ringbom plots was 0.7–7.7 μg mL−1. The molar absorptivity, Sandell sensitivity, and detection limit were also calculated. The most optimal and sensitive method was developed using BCG. The correlation coefficient was 0.9988 (n = 6) with a relative standard deviation of 1.25, for six determinations of 4.0 μg mL−1. The proposed methods were successfully applied to the determination of fluoxetine hydrochloride in its dosage forms and in biological fluids (spiked plasma sample) using the standard addition technique.

A new method for saccharin determination in liquid sweetener products was developed. The method is based on the precipitation reaction of Ag(I) ions with saccharin in aqueous medium (pH 3.0), using a flow injection analysis system with merging zones, the suspension was stabilized with 5 g L−1 Triton X-100. All experimental parameters influencing the flow injection system were optimized by means of chemometric approaches. The linear analytical curve was built from 2.4 g L−1 up to 9.64 g L−1 (r = 0.9968) with a quantification limit of 2.40 g L−1. The precision assessed as relative standard deviation (n = 10) was found to be 1.75 % for the saccharin concentration of 7.20 g L−1. Based on interference studies performed with the substances commonly found in liquid sweeteners, such as sodium cyclamate, methylparaben, sodium aspartame, and benzoic and citric acids, at the analyte to interferent mole ratio of up to 1: 10, no interference with the saccharin determination was observed. The presence of chloride ions interferes with the method, but a preceding liquid-liquid saccharin extraction with ethyl acetate was successfully employed to overcome this drawback. Accuracy of the method in sweetener products was evaluated by a comparison with the HPLC method.

This paper describes two isotachophoretic methods of metoprolol tartrate (MT) determination in pure and dosage forms. The first method was used for direct analysis where the following electrolyte system was applied: 10 mmol dm−3 3-morpholino-2-hydroxypropanesulfonic acid, 10 mmol dm−3 NaCl, 2 % hydroxyethylocelulose as leading (LE) and 10 mmol dm−3 glycyl-glycine as terminating (TE) electrolytes. The second method was used for indirect analysis of MT as tartrate ions. In this case, the leading electrolyte consisted of 10 mmol dm−3 HCl, β-alanine (BALA), pH 4-5, and the terminating one of 5 mmol dm−3 glutamic acid, 10 mmol dm−3 β-alanine. Calibration curves were calculated as follows: for system A: y = (0.52 ± 0.05)x − (0.9 ± 0.2) (LOD = 13.0 mg dm−3, LOQ = 31.7 mg dm−3); and for system B: y = (0.240 +- 0.001)x + (0.18 ± 0.06) (LOD = 1.8 mg dm−3, LOQ = 4.4 mg dm−3). The isotachophoretic method was compared with the pharmacopoeial one by statistical tests.

This paper presents a case study of model predictive control (MPC) applied to a continuous stirred tank reactor (CSTR). It is proposed to approximate nonlinear behavior of a plant by several local linear models, enabling a piecewise affine (PWA) description of the model used to predict and optimize future evolution of the reactor behavior. Main advantage of the PWA model over traditional approaches based on single linearization is a significant increase of model accuracy which leads to a better control quality. It is also illustrated that, by adopting the PWA modeling framework, MPC strategy can be implemented using significantly less computational power compared to nonlinear MPC setups.

Simulation of a hydrocarbons mixture separation by extractive distillation was based on binary vapor-liquid as well as liquid-liquid equilibrium data. Sulfolane was considered as extractive solvent for the selective toluene separation from a model mixture with heptane. For simulation of the chosen hydrocarbons mixture separation in the presence of an extractive solvent, the NRTL model was considered. A set of temperature-dependent binary NRTL parameters was evaluated independently by fitting the experimental vapor-liquid and liquid-liquid equilibrium data of the respective binary subsystems. In order to improve the description of the ternary vapor-liquid equilibrium, original NRTL model extended by the ternary contribution term was used. Parameters of the ternary contribution were obtained by direct fitting of available ternary liquid-liquid equilibrium data while employing the original binary NRTL parameters. Quality of the ternary vapor-liquid-liquid equilibrium description using the original and the extended excess Gibbs energy models was assessed by comparing the calculated compositions of conjugate liquid phases with experimental data. Using the extended NRTL model, mean deviation of the computed mole fractions decreased by approximately four times (9.73 × 10−3) compared to the value obtained using the original NRTL model. Both original and extended NRTL models were employed for the simulation of a model mixture separation by extractive distillation. At chosen experimental conditions, high purity distillate (x 1 > 0.999) was obtained. Results of the aromatics extractive distillation in the presence of sulfolane were compared to those obtained with N-methylpyrrolidone as the extractive solvent.

A novel series of Co(II), Ni(II), Cu(II), Zn(II), and VO(IV) complexes has been synthesized from the Schiff base derived from 4-[(3,4-dimethoxybenzylidene)amino]-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one and 1,2-diaminobenzene. Structural features were determined by analytical and spectral techniques. Binding of synthesized complexes with calf thymus DNA (CT DNA) was studied by spectroscopic methods and viscosity measurements. Experimental results indicate that the complexes are able to form adducts with DNA and to distort the double helix by changing the base stacking. Lower DNA affinity of the VO(IV) complex is caused by the change of coordination geometry by the vanadyl ion resulting in a somewhat unfavorable configuration for the DNA binding. Oxidative DNA cleavage activities of the complexes were studied with supercoiled (SC) pUC19 DNA using gel electrophoresis; the mechanism studies revealed that the hydroxyl radical is likely to be the reactive species responsible for the cleavage of pUC19 DNA by the synthesized complexes. The in vitro antimicrobial screening effects of the investigated compounds were monitored by the disc diffusion method. The synthesized Schiff base complexes exhibit higher antimicrobial activity than the respective free Schiff base.

New 4-cyanopyridine halide and mixed-halide Cu4OBrnCl(6−n)(4-CNpy)4 complexes (4-CNpy = 4-cyanopyridine, n = 0–6) were synthesised, characterised, and studied by infrared spectra, electronic spectra, and cyclic voltammetry. Infrared spectra revealed donor-acceptor vibrational couplings of the Cu4O, Cu-Cl, and Cu-N stretching vibrations with the in-plane and out-of-plane pyridine ring vibrations. The infrared spectra, electronic spectra, and half-wave potentials correspond to a weak donor and a strong acceptor behaviour of the 4-cyanopyridine ligands and to π-back bonding, Cu(II)→pyridine rings. The results were compared with the related pyridine and 4-substituted pyridine complexes.

Seven new 3-cyanopyridine Cu4OBrnCl(6−n)(3-CNpy)4 (n = 0–6) complexes were prepared and studied by infrared spectra, electronic spectra, and cyclic voltammetry. Infrared spectra revealed a distortion of the tetrahedral Cu4O core to C 2ν or C 3ν symmetries and a donor-acceptor vibrational coupling with the in-plane pyridine ring bending within the O-Cu-(pyridine ring)CN system involving the π-back bonding between Cu(II) atoms and 3-CNpy ligands. Bands of the electronic spectra and half-wave potentials of the complexes are consistent with the weak donor and strong acceptor behaviour of the 3-CNpy ligands. The results were compared with analogous complexes of pyridine, 3-substituted and 4-substituted pyridine ligands.

Therapeutic activity of locally applied drugs depends on both the thermodynamic activity of the active molecule and the pharmaceutical system which enables the release of the molecule; also the vasoconstrictive activity of vessels plays an important role. In this study, the release of chlorhexidine was assessed considering the use of ionic and non-ionic polymeric carriers at temperatures in the range between 22°C and 42°C, including the temperature of 32°C as the reference surface body temperature. The obtained release rates and concentrations of chlorhexidine, loaded to methylcellulose and poly(acrylic acid) gels, were compared with respective viscositiy, pH, and conductivity of the assessed systems. The deposition patterns of chlorhexidine in the polymeric matrix were studied using energy dispersive X-ray spectrometry to evaluate the possible influence of chlorhexidine distribution in/on the carrier on the respective release rates. This study is significant for patients with various skin temperature conditions, who are required to receive local biocides applied on skin or into the oral cavity. The obtained precipitate of polyacrylic acid-chlorhexidine preparation was extensively studied to evaluate the chlorhexidine release and to develop an application in skin and dental care.

A series of new coumarin derivatives has been synthesized by condensation of 4-chloro-3-nitrocoumarin and the appropriate arylamine and sulfonamide in ethyl acetate in the presence of triethylamine. The synthesized compounds were screened for their in vitro antimicrobial activity against thirteen strains of bacteria and three fungal/yeast strains using disk diffusion assays. They were shown to possess a wide range of activities from almost completely inactive compounds to medium active ones. (4-[(5-Chloropyridin-2-yl)amino]-3-nitro-2H-chromen-2-one) showed similar activity against Klebsiella pneumoniae as tetracycline.

An efficient Knoevenagel route using green chemistry conditions was applied for the synthesis of halogen- and cyano- substituted pyridinevinylene compounds. Absorption and fluorescence emission spectra of these conjugated compounds were recorded and compared in order to evaluate the effect of substituents on the electronic properties of pyridinevinylene compounds. The substituents studied were terminal Cl and F, two or three aromatic rings, as well as a cyano group attached to a C=C double bond. The compounds synthesized are: (E)-2-(4-fluorostyryl)pyridine, (E)-2-(4-chlorostyryl)pyridine, (E)-4-(4-chlorostyryl)pyridine, 2,3-diphenylacrylonitrile, 3-phenyl-2-(pyridin-2-yl)acrylonitrile, 3-phenyl-2-(pyridin-3-yl)acrylonitrile, 2-phenyl-3-(pyridin-2-yl)acrylonitrile, 3,3′-(1,4-phenylene)bis(2-phenylacrylonitrile), 3,3′-(1,4-phenylene)bis(2-(pyridin-2-yl)acrylonitrile), and 3,3′-(1,4-phenylene)bis(2-(pyridin-3-yl)acrylonitrile). The solvent-free method used in this work allows obtaining each compound by controlling the reaction temperature. The compounds were characterized by infrared spectroscopy and 1H-NMR spectroscopy.

The present study gives results of chemical composition analyses and antimicrobial activity testing of three Erodium species: E. ciconium L., E. cicutarium L., and E. absinthoides Willd. Essential oils were obtained by hydro-distillation from air-dried entire plants and analyzed by GC and GC-MS. A total of 209 different compounds were identified: 162 for E. cicutarium, 107 for E. ciconium, and 79 for E. absinthoides. Antimicrobial activity (broth microdilution method) of the oils was screened against a panel of Gram positive and Gram negative bacteria and a number of fungi. Moderate susceptibility of all tested strains was observed. Determined MIC values were 0.156–5 mg mL−1 (bacterial strains) and 0.039–0.325 mg mL−1 (fungal strains). Major component of the most active oil, palmitic acid, was also tested for activity together with stearic and myristic acids.

Degradation of methyl orange (MO) was carried out by the photo-Fenton process (Fe2+/H2O2/UV) and photo-Fenton-like processes (Fe3+/H2O2/UV, Fe2+/S2O82−/UV, and Fe3+/S2O82−/UV) at the acidic pH of 3 using hydrogen peroxide and ammonium persulfate (APS) as oxidants. Oxidation state of iron had a significant influence on the efficiency of photo-Fenton/photo-Fenton-like processes. It was found that a process with a source of Fe3+ ions as the catalyst showed higher efficiency compared to a process with the Fe2+ ion as the catalyst. H2O2 served as a better oxidant for both oxidation states of iron compared to APS. The lower efficiency of APS is attributed to the generation of excess protons which scavenges the hydroxyl radicals necessary for degradation. Further, the sulfate ions produced from S2O82− form a complex with Fe2+/Fe3+ ions thereby reducing the concentration of free iron ions in the solution. This process can also reduce the concentration of hydroxyl radicals in the solution. Efficiency of the various MO degradation processes follows the order: Fe3+/H2O2/UV, Fe3+/APS/UV, Fe2+/H2O2/UV, Fe2+/APS/UV.

Electrochemical behavior of resazurin on HMDE in Britton-Robinson (B-R) buffers (pH 2.0–10.0) was studied using the square-wave voltammetry (SWV), square-wave adsorptive stripping voltammetry (SWAdSV), and cyclic voltammetry (CV) techniques. The voltammogram of resazurin in B-R buffer at pH < 4.0 exhibited two cathodic reduction peaks. The voltammetric peaks were obtained at −0.144 V (reversible) and −1.250 V (irreversible) at pH 3.2, and correspond to the reduction of resorufin to dihydroresorufin and to the catalytic hydrogen wave, respectively. At pH > 4.0, a new irreversible cathodic reduction peak, assigned to the protonation of N-oxide on the phenoxazin ring, was observed. Electrochemical parameters (I p/E p, I p/v, I p/pH, I p/t acc) of the compound were determined. From the voltammetric data, electrochemical reduction mechanisms for all peaks have been suggested. Maximum peak current for the reversible peak was obtained at pH 4.1. A linear relationship between the current and concentration was determined, and also the lowest detection limit was found as 3.25 × 10−8 mol L−1 and 1.98 × 10−10 mol L−1 for SWV and SWAdSV, respectively.

The Becke3LYP density functional was used to study structural and thermodynamic parameters of bivalent zinc cation complexes with selected substrates and ACE inhibitors (H2O/OH−, neutral forms of captopril, zofenoprilat, omapatrilat, CH3CONHCH3, and N-terminal anions of captopril, zofenoprilat, omapatrilat, enalaprilat, perindoprilat, trandolaprilat, and fosinoprilat). The combination of DFT and the conductor-like polarizable continuum model (CPCM) were employed to compute the Gibbs interaction energies (ΔG) between Zn2+ and the selected ACE inhibitors for dielectric media with ɛ = 5 (to simulate the protein environment) and for water media (ɛ = 78.39) for comparison purposes. The results show that ΔG is sensitive to the dielectric constant of the environment and that lower dielectric medium favors the binding of inhibitors to the zinc cation.

The present paper deals with the evaluation of nimesulide, 2-phenoxy-4-nitroaniline, the main hydrolytic degradation product of nimesulide, of methylparaben and propylparaben, and eventually of 4-hydroxybenzoic acid by HPLC with UV detection at 254 nm in syrup as a pharmaceutical formulation. HPLC analysis was employed on the reversed phase C18 with methanol and 0.01 M dibasic ammonium phosphate (ρ r = 60: 40, pH 4.0). Validation was performed using standards and a pharmaceutical preparation containing the compounds described above.