Sibel A. Ozkan

Analysis of Pharmaceuticals and Biological Fluids Using Modern Electroanalytical Techniques

A review of the principles and application of modern electroanalytical techniques, namely, cyclic voltammetry, linear sweep voltammetry, differential pulse voltammetry, differential pulse polarography, square wave voltammetry, square wave polarography, stripping voltammetric, and stripping polarographic techniques, is presented. The use and advantages of these techniques at different electrodes are discussed. The analytical applications of these techniques to pharmaceutical compounds in dosage forms and biological media are also discussed. Various selected studies on these subjects since 1995 are reviewed.

Enhanced bioavailability of piroxicam using Gelucire 44/14 and labrasol: in vitro and in vivo evaluation.

Piroxicam is a non-steroidal anti-inflammatory drug that is characterized by low solubility and high permeability. The purpose of the study was to investigate the in vitro and in vivo performance of the semi-solid dispersion prepared with Gelucire 44/14 and Labrasol into hard gelatin capsules (GL) for enhancing the dissolution rate of the drug. The results were evaluated by comparing with pure piroxicam filled into hard gelatin capsules (PP) and a commercially available tablet dosage form containing a piroxicam:beta-cyclodextrin complex (CD). The in vitro dissolution testing of the dosage forms was performed in different media (simulated gastric fluid, pH 1.2; phosphate buffers, pH 4.5 and 6.8; and water). Amongst the dosage forms, GL provided at least 85% piroxicam dissolution within 30 min in each of the media, behaving like a fast-dissolving immediate release drug product. Oral bioavailability of 20 mg piroxicam in GL, CD, and PP was compared after administration of a single dose to eight healthy volunteers. Three treatments were administered in crossover fashion, separated by a washout period of 2 weeks. Piroxicam was monitored in plasma by high-performance liquid chromatography. The apparent rate of absorption of piroxicam from GL (Cmax=2.64 micrograms/ml, tmax=82.5 min) was significantly higher than that of the PP (Cmax=0.999 micrograms/ml, tmax=144 min) (P<0.05) and similar to that of CD (Cmax=2.44 micrograms/ml, tmax=120 min) (P>0.05). The relative bioavailability values as the ratios of mean total AUC for GL relative to PP and CD, were 221 and 98.6%. Piroxicam is characterized by a slow and gradual absorption via the oral route and this causes a delayed onset of therapeutic effect. Thus, plain piroxicam preparations are not indicated for analgesia. The results of the in vivo study revealed that the GL dosage form would be advantageous with regards to rapid onset of action, especially in various painful conditions where an acute analgesic effect is desired.

Simultaneous determination of valsartan and hydrochlorothiazide in tablets by first-derivative ultraviolet spectrophotometry and LC.

First-derivative ultraviolet spectrophotometry and high-performance liquid chromatography (HPLC) were used to determine valsartan and hydrochlorothiazide simultaneously in combined pharmaceutical dosage forms. The derivative procedure was based on the linear relationship between the drug concentration and the first derivative amplitudes at 270.6 and 335 nm for valsartan and hydrochlorothiazide, respectively. The calibration graphs were linear in the range of 12.0-36.1 microg x ml(-1) for valsartan and 4.0-12.1 microg x ml(-1) for hydrochlorothiazide. Furthermore, a high- performance liquid chromatographic procedure with ultraviolet detection at 225 nm was developed for a comparison method. For the HPLC procedure, a reversed phase column with a mobile phase of 0.02 M phosphate buffer (pH 3.2)-acetonitrile (55: 45; v/v), was used to separate for valsartan and hydrochlorothiazide. The plot of peak area ratio of each drug to the internal standard versus the respective concentrations of valsartan and hydrochlorothiazide were found to be linear in the range of 0.06-1.8 and 0.07-0.5 microg x ml(-1), respectively. The proposed methods were successfully applied to the determination of these drugs in laboratory-prepared mixtures and commercial tablets.

Electroanalytical Application of Carbon Based Electrodes to the Pharmaceuticals

Abstract Carbon and its derivatives, as the high performance material, occupy a special place in electrochemistry due to its ‐in many ways‐ extreme properties. Recent trends and advances in the electrochemistry of carbon‐based electrodes are reviewed. The varieties of carbon‐based electrodes, their basic physicochemical properties and some characteristics are surveyed. Special attention is paid to the possibilities of carbon‐based electrodes in electroanalytical investigation in pharmaceutical dosage forms and biological samples using modern electrochemical techniques. This review includes a summary of the rules that must be considered for drug analysis from its dosage forms and biological samples using carbon‐based electrodes. The present review is the first comprehensive report on the heterogeneous and homogeneous carbon electrodes, and an addition to many excellent reviews on carbon electrodes in the literature. This review summarizes some of the recent developments and applications of carbon‐based electrodes for drug compounds in their dosage forms and in biological samples in the period from 1996 till 2006. Also some further selected designs (screen‐printed; carbon nanotubes, etc.) and applications have been discussed.

SIMULTANEOUS DETERMINATION OF PARACETAMOL AND METHOCARBAMOL IN TABLETS BY RATIO SPECTRA DERIVATIVE SPECTROPHOTOMETRY AND LC

The application of the ratio spectra derivative spectrophotometry and high-performance liquid chromatography (HPLC) to the simultaneous determination of paracetamol (PAR) and methocarbamol (MET) in combined pharmaceutical tablets is presented. The spectrophotometric procedure is based on the use of the first derivative of the ratio spectra obtained by dividing the absorbtion spectrum of the binary mixtures by a standard spectrum of one of the compounds. The first derivative amplitudes were measured at 243.0 and 230.3 nm for the assay of PAR and MET, respectively. Calibration graphs were established for 2-30 microg ml for PAR and 2-36 microg/ml for MET in binary mixture. The detection limits for PAR and MET were found 0.097 and 0.079 microg/ml, respectively; while the quantification limits were 0.573 microg/ml for PAR and 1.717 microg/ml for MET. For the HPLC procedure, a reversed-phase column with a mobile phase of methanol-water (60:40, v/v), was used to separate both compounds with a detection of 274.0 nm. Linearity was obtained in the concentration range of 2 300 and 1.5-375 microg/ml for PAR and MET, respectively. The detection and quantification limits were found to be 0.42 and 1.4 microg/ml for PAR and 0.36 and 1.2 microg/ml for MET, respectively. The relative standard deviations were found to be less than 0.52%, indicating reasonable repeatibility of both methods. The proposed methods were successfully applied to the determination of these drugs in commercial tablets.

Solid Electrodes in Electroanalytical Chemistry: Present Applications and Prospects for High Throughput Screening of Drug Compounds

This review summarizes recent progress in the development and application of solid electrodes to the screening of pharmaceutical dosage forms and biological fluids. Recent trends and advances in the electroanalytical chemistry of solid electrodes, microelectrodes and electrochemical sensors are reviewed. The varieties of solid electrodes and their basic physico-chemical properties and some specific characteristics including some supramolecular phenomena at their surface are surveyed. This review also includes some selected designs and their applications. Despite many reviews about individual solid electrodes in the literature, this review offers the first comprehensive report on all forms of solid electrodes. Special attention is paid to the possibilities of solid electrodes in high throughput electroanalytical investigation of drug dosage forms and biological samples using modern electroanalytical techniques. Various selected studies on these subjects since 1996 are reviewed in this paper.

Anodic voltammetric behavior and determination of cefixime in pharmaceutical dosage forms and biological fluids.

The voltammetric behavior of cefixime was studied using cyclic, linear sweep, differential pulse and square wave voltammetric techniques. The oxidation of cefixime was irreversible and exhibited diffusion controlled process depending on pH. The oxidation mechanism was proposed and discussed. Different parameters were tested to optimize the conditions for the determination of cefixime. The dependence of current intensities and potentials on pH, concentration, scan rate, nature of the buffer was investigated. According to the linear relationship between the peak current and the concentration, differential pulse (DPV) and square wave (SWV) voltammetric methods for cefixime assay in pharmaceutical dosage forms and biological fluids were developed. For the determination of cefixime were proposed in acetate buffer at pH 4.5, which allows quantitation over the 6 x 10(-6)-2 x 10(-4)M range in supporting electrolyte and spiked serum sample; 8 x 10(-6)-2 x 10(-4)M range in urine sample; 6 x 10(-6)-1 x 10(-4)M range in breast milk samples for both techniques. The repeatability, reproducibility, precision and accuracy of the methods in all media were investigated. No electroactive interferences from the excipients and endogenous substances were found in the pharmaceutical dosage forms and in the biological samples, respectively.

Electrochemical reduction of metronidazole at activated glassy carbon electrode and its determination in pharmaceutical dosage forms.

A voltammetric method has been developed for the determination of metronidazole in dosage forms. The method is based on the electrochemical reduction of the drug at a glassy carbon electrode activated by applying a new pretreatment. The influence of pH, concentration, scan rate and presence of organic solvent and surfactant has been studied. The current is proportional to the concentration and permits the drug to be determined in the concentration range 2 x 10(-6)-6 x 10(-4) M in Britton-Robinson buffer (pH 10). Furthermore, results obtained by the proposed method have been compared with USP XXIII procedure which involves a HPLC method.

Electroanalytical Methods for the Determination of Pharmaceuticals: A Review of Recent Trends and Developments

Electroanalysis is a powerful analytical technique that is increasing in utility in the pharmaceutical industry. It is used as an alternative or complementary technique to spectrophotometric and separation techniques due to its high sensitivity, speed of analysis, reduction in solvent and sample consumption, and low operating cost compared to other analytical methods. A review of the principles and application of modern electroanalytical techniques, namely, cyclic, linear sweep, differential pulse, square wave and stripping voltammetric techniques, is presented. This review gives recent pharmaceutical analysis applications used for each mode of electroanalytical chemistry. The review will also describe recent developments for enhancing concentration limits of detection, electrode types, and so forth. Selected studies on these subjects are given as examples.

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.