Mehmet Gumustas

Electroanalytical characteristics of antipsychotic drug ziprasidone and its determination in pharmaceuticals and serum samples on solid electrodes.

Ziprasidone is a psychotropic agent used for the treatment of schizophrenia. Its oxidation was investigated electrochemically at boron-doped diamond and glassy carbon electrodes using cyclic, differential pulse, and square wave voltammetry. The dependence of the peak current and peak potentials on pH, concentration, nature of the buffer, and scan rate were examined. The process was diffusion and adsorption controlled for boron-doped diamond and glassy carbon electrodes, respectively. The possible mechanism of oxidation was discussed with some model compounds that have indole and piperazine oxidations. A linear response was obtained between 8 x 10(-7) and 8 x 10(-5) M for the first peak in acetate buffer (pH 5.5) and between 2 x 10(-6) and 2 x 10(-4) M for the second peak in 0.1 M H(2)SO(4) with boron-doped diamond electrode for differential pulse and square wave voltammetric techniques. The reproducibility and accuracy of the proposed methods were found between 0.31 and 1.20, 99.27 and 100.22, respectively. The recovery studies were also achieved to check selectivity and accuracy of the methods. The proposed methods were applied for the determination of ziprasidone from pharmaceutical dosage forms and human serum samples without any time-consuming extraction, separation, evaporation or adsorption steps prior to drug assay except precipitation of the proteins using acetonitrile. The results were statistically compared with those obtained through an established LC-UV technique, no significant differences were been found between the voltammetric and LC methods.

The Role of and the Place of Method Validation in Drug Analysis Using Electroanalytical Techniques

Electroanalytical methods are chosen for the sensitive analysis of pharmaceutically active compounds in their dosage forms and biological samples. Electroanalytical method validation is the process used to confirm that the determination procedure employed for a specific test is suitable for its intended use like other analytical methods. Results from electroanalytical method validation can be used to judge the quality, applicability, accuracy, reliability and

Determination of pKa values of some antihypertensive drugs by liquid chromatography and simultaneous assay of lercanidipine and enalapril in their binary mixtures

In this study, pK(a) values were determined using the dependence of the retention factor on the pH of the mobile phase for three ionizable substances, namely, enalapril, lercanidipine and ramipril (IS). The effect of the mobile phase composition on the ionization constant was studied by measuring the pK(a) at different methanol-water mixtures, ranging between 50 and 65% (v/v), using LC-DAD method. Two simple, accurate, precise and fully validated analytical methods for the simultaneous determination of enalapril and lercanidipine in combined dosage forms have been developed. Separation was performed on an X-Terra RP-18 column (250 mm x 4.60mm ID x 5 microm) at 40 degrees C with the mobile phase of methanol-water 55:45 (v/v) adjusted to pH 2.7 with 15 mM orthophosphoric acid. Isocratic elution was performed in less than 12 min with a flow rate of 1.2 mL min(-1). Good sensitivity for the analytes was observed with DAD detection. The LC method allowed quantitation over the 0.50-20.00 microg mL(-1) range for enalapril and lercanidipine. The second method depends on first derivative of the ratio-spectra by measurements of the amplitudes at 219.7 nm for enalapril and 233.0 nm for lercanidipine. Calibration graphs were established for 1-20 microg mL(-1) for enalapril and 1-16 microg mL(-1) lercanidipine, using first derivative of the ratio spectrophotometric method. Both methods have been extensively validated. These methods allow a number of cost and time saving benefits. The described methods can be readily utilized for analysis of pharmaceutical formulations. The methods have been applied, without any interference from excipients, for the simultaneous determination of these compounds in tablets. There was no significant difference between the performance of the proposed methods regarding the mean values and standard deviations.

Voltammetric and RP-LC assay for determination of benidipine HCl

The detailed electrooxidative behavior of benidipine (BEN) has been studied by using glassy carbon (GC) and boron-doped diamond (BDD) electrodes. Using cyclic voltammetry, depending on the pH values and the working electrodes, BEN showed one or two sharp and irreversible oxidation responses. The voltammetric experiments on some model compounds allowed elucidation of the oxidation mechanism of BEN. Highly sensitive, selective, rapid, and fully validated voltammetric methods for the determination of BEN in tablet dosage form were also presented. Under optimized conditions, the peak current showed a linear dependence with concentration in the range between 3.25 μg mL(-1) and 54.20 μg mL(-1) for GC and 1.08 μg mL(-1) and 54.20 μg mL(-1) for BDD electrodes by using differential pulse (DPV) and square wave (SWV) voltammetric techniques. In this study, acid dissociation constant (pK(a)) value of BEN was determined by using the dependence of the retention factor on the pH of the mobile phase using reverse phase-liquid chromatographic (RP-LC) method. The effect of the composition of the mobile phase on the ionization constant was studied by measuring the pK(a) at different acetonitrile-water mixtures, ranging between 50 and 65% (v/v). Also simple, accurate, precise and fully validated RP-LC method for the assay of BEN in dosage form has been developed. XTerra RP-18 column at 25 °C with the mobile phase of acetonitrile:water 55:45 (v/v) adjusted to pH 3.0 with 15 mM o-phosphoric acid was used. Isocratic elution was performed in less than 5.0 min with a flow rate of 1.0 mL min(-1). The RP-LC method allowed quantitation over the 0.25-15.00 μg mL(-1) range for BEN. The proposed voltammetric and RP-LC methods allow a number of cost and time saving benefits. BEN was also exposed to thermal, photolytic, oxidative stress, acid-base catalyzed hydrolyses, and the stressed samples were detected by the proposed RP-LC method.

Dynamic computer simulation of electrophoretic enantiomer migration order and separation in presence of a neutral cyclodextrin

One‐dimensional dynamic computer simulation was employed to investigate the separation and migration order change of ketoconazole enantiomers at low pH in presence of increasing amounts of (2‐hydroxypropyl)‐β‐cyclodextrin (OHP‐β‐CD). The 1:1 interaction of ketoconazole with the neutral cyclodextrin was simulated under real experimental conditions and by varying input parameters for complex mobilities and complexation constants. Simulation results obtained with experimentally determined apparent ionic mobilities, complex mobilities, and complexation constants were found to compare well with the calculated separation selectivity and experimental data. Simulation data revealed that the migration order of the ketoconazole enantiomers at low (OHP‐β‐CD) concentrations (i.e. below migration order inversion) is essentially determined by the difference in complexation constants and at high (OHP‐β‐CD) concentrations (i.e. above migration order inversion) by the difference in complex mobilities. Furthermore, simulations with complex mobilities set to zero provided data that mimic migration order and separation with the chiral selector being immobilized. For the studied CEC configuration, no migration order inversion is predicted and separations are shown to be quicker and electrophoretic transport reduced in comparison to migration in free solution. The presented data illustrate that dynamic computer simulation is a valuable tool to study electrokinetic migration and separations of enantiomers in presence of a complexing agent.

Electrochemical Behavior of Indole-3-Carboxaldehyde Izonicotinoyl Hydrazones: Discussion on Possible Biological Behavior

Electrochemical techniques provide valuable information about drug molecules and their mechanisms in the body such as metabolism is getting one of the important actions in drug discovery. Since many physiological processes are depending on oxido-reduction reactions, it is not difficult to find associations between electrochemical and biological reactions regarding electron transfers. To investigate this proposal two compounds namely 1-methylindole-3-carboxaldehyde izonicotinoyl hydrazone and 5-chloro-1H-indole-3-carboxaldehyde izonicotinoyl hydrazone were synthesized, characterized and examined electrochemically using different voltammetric techniques in order to evaluate the possible biological behavior. The characteristics of the corresponding electrode reaction were discussed. A linear response was obtained in the different media for the compounds with low detection limits of the synthesized compounds.

Preparation and Characterization of Chitosan-Based Spray-Dried Microparticles for the Delivery of Clindamycin Phosphate to Periodontal Pockets

Biodegradable spray-dried chitosan microparticles loaded with clindamycin phosphate (CDP) were formulated to deliver drugs locally into the periodontal pocket. The effects of spray dryer conditions, drug/polymer ratio, and added amounts of glutaraldehyde (GA) solution on the characterization of microparticles were investigated by determining process yield, encapsulation efficiency, particle size and size distribution, surface morphology, drug release, release kinetics, thermal analysis, and antimicrobial efficacy of formulations. Burst release was obtained for all formulations due to the water solubility of the drug, but the increased amount of chitosan decreased the drug release rates. Microparticles with a more wrinkled surface were obtained by increasing the amount of the drug. Incorporation efficiencies higher than 80% were obtained for all preparation conditions. The addition of GA caused higher viscosity of the chitosan solution, leading to larger particles with more spherical and smooth surface characteristics. However, the increased GA amount did not significantly influence the drug release. The data obtained from in vitro release experiments were best fitted to the Weibull and Higuchi models. The amorphous nature of the drug-loaded microparticles was detected by differential scanning calorimetric (DSC) thermographs. A delayed drug release of more than one week could be obtained by loading the drug into the chitosan microparticles. Antimicrobial efficacy studies reflected a positive drug release profile. These results indicate that spray-dried clindamycin-loaded microparticles with sustained antimicrobial efficacy appear to be a promising periodontal therapy for drug delivery into the periodontal pocket.

Separation and elution order of the enantiomers of some β-agonists using polysaccharide-based chiral columns and normal phase eluents by high-performance liquid chromatography.

In this study separation of enantiomers of 8 chiral β-agonists were studied on 6 polysaccharide-based chiral columns in polar-organic and alcohol-hydrocarbon mobile phases. No separation of enantiomers was observed on any column with polar-organic mobile phase eluents such as pure methanol, ethanol or acetonitrile. Most of the chiral analytes were resolved into enantiomers when alcohol-hydrocarbon type mobile phases were used. The most successful column was Lux Cellulose-2 on which all 8 chiral analytes were baseline resolved into enantiomers at least with one mobile phase used. The reversal of enantiomer elution order was observed dependent on the chemistry of the chiral selector and the composition of the mobile phase.

Optimization of a validated stability‐indicating RP‐LC method for the determination of fulvestrant from polymeric based nanoparticle systems, drugs and biological samples

Fulvestrant is used for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. Several reversed-phase columns with variable silica materials, diameters, lengths, etc., were tested for the optimization study. A good chromatographic separation was achieved using a Waters X-Terra RP(18) column (250 × 4.6 mm i.d. × 5 µm) and a mobile phase, consisting of a mixture of acetonitrile-water (65:35; v/v) containing phosphoric acid (0.1%). The separation was carried out 40 °C with detection at 215 nm.The calibration curves were linear over the concentration range between 1.0-300 and 1.0-200 µg/mL for standard solutions and biological media, respectively. The proposed method is accurate and reproducible. Forced degradation studies were also realized. This fully validated method allows the direct determination of fulvestrant in dosage form and biological samples. The average recovery of the added fulvestrant amount in the samples was between 98.22 and 104.03%. The proposed method was also applied for the determination of fulvestrant from the polymeric-based nanoparticle systems. No interference from using polymers and other excipients was observed in in vitro drug release studies. Therefore an incorporation efficiency of fulvestrant-loaded nanoparticle could be determined accurately and specifically.

Simultaneous estimation and validation of some binary mixtures of antihypertensive drugs by RP-LC methods using two new generation silica columns

Two reversed phase liquid chromatographic (RP-LC) techniques are presented for the rapid, accurate, precise, simultaneous determination of olmesartan-hydrochlorothiazide and zofenopril-hydrochlorothiazide binary mixtures in their dosage forms. The separation of these binary mixtures was carried out by using two new stationary phases that have different surface chemistries which were used for the first time in the determination of these binary mixtures. The analyte peaks were detected at 216 nm. Linearity was obtained in different concentration ranges between 0.5 and 20 μg mL(-1) for all compounds. The proposed methods have been extensively validated and sample preparation, flow rate, run time of the analytical systems were at low levels. The proposed methods would decrease the consumption of organic solvents and reagents further safeguarding to our environment.