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The electrochemical properties of valacyclovir, an antiviral drug, were investigated in pH range 1.8-12.0 by cyclic, differential pulse and square-wave voltammetry. The drug was irreversibly oxidized at a glassy carbon electrode in one or two oxidation steps, which are pH-dependent. For analytical purposes, a very resolved diffusion controlled voltammetric peak was obtained in Britton-Robinson buffer at pH 10.0 using differential pulse and square-wave modes. Limits of detection were 1.04 x 10(-7) and 4.60 x 10(-8) M for differential pulse and square-wave voltammetry, respectively. The applicability to direct assays of tablets, spiked human serum and simulated gastric fluid, was described. (c) 2005 Elsevier B.V. All rights reserved.

A simple, rapid, specific, sensitive HPLC method has been developed for the determination of piroxicam in the tablet dosage form and in human plasma. The method totally eliminates solvent extraction and time-consuming separation procedures. Plasma proteins were precipitated by addition of 3:1 (v/v) acetonitrile-methanol, ZnSO4, and MgSO4 and the supernatant was injected directly on to a 250 mm × 4.6 mm, 5 μm particle Spherisorb analytical column. Acetonitrile-methanol-0.04 mol L−1 KH2PO4, 40:10:50 (v/v); pH 3.8, was used as mobile phase. The drug was detected by UV detection at 330 nm. The response was linear over the range of 0.01–10 μg mL−1 and 0.025–5 μg mL−1 in mobile phase and human plasma samples, respectively. The proposed method was used without interference from the endogenous substances, for determination of piroxicam in plasma samples obtained from healthy volunteers. The results revealed that the method would be useful in monitoring plasma levels of the drug during pharmacokinetic studies. Assay of piroxicam in its dosage forms for quality-control purposes could also be performed successfully by use of this method.

The electrochemical oxidation of antipsychotic drug amisulpride (AMS) has been studied in pH range 1.8–11.0 at a stationary glassy carbon electrode by cyclic, differential pulse and square-wave voltammetry. Two oxidation processes were produced in different supporting electrolyte media. Both of the oxidation processes were irreversible and exhibited diffusion controlled. For analytical purposes, very resolved voltammetric peaks were obtained using differential pulse and square-wave modes. The linear response was obtained in the range of 4×10−6 to 6×10−4 M for the first and second oxidation steps in Britton-Robinson buffer at pH 7.0 and pH 3.0 (20% methanol v/v), respectively, using both techniques. These methods were used for the determination of AMS in tablets. The first oxidation process was chosen as indicative of the analysis of AMS in biological media. The methods were successfully applied to spiked human serum, urine and simulated gastric fluid samples.

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) (P0.05) and similar to that of CD (Cmax=2.44 micrograms/ml, tmax=120 min) (P0.05). 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.

The electrochemical oxidative behavior of piribedil (PR) was described. It was investigated by cyclic, linear sweep, differential pulse (DPV) and square wave (SWV) voltammetric techniques. The redox behavior of PR was found irreversible. Different parameters were tested to optimize the conditions for the determination of PR. The dependence of intensities of currents and potential on pH, concentration, scan rate, nature of the buffer was investigated. Two sensitive methods for the measurement of PR were described. For analytical purposes, a very well resolved diffusion controlled voltammetric peak was obtained in 0.1 M H(2)SO(4) and pH 5.7 acetate buffer. The determination peaks are obtained at 1.27 and 0.95 V for differential pulse and 1.29 and 0.97 V for SWV in 0.1 M H(2)SO(4) and pH 5.7 acetate buffer, respectively. The linear response was obtained in the ranges of 2 x 10(-6)-1 x 10(-3) M in 0.1 M H(2)SO(4) and 2 x 10(-6)-8 x 10(-4) M in pH 5.7 acetate buffer for both techniques. The proposed techniques were successfully applied to the determination of PR in tablet dosage forms and human serum. Excipients did not interfere in the determination. The necessary statistical validation reveals that the proposed methods are free from significant systematic errors.

A detailed study of the electrochemistry of ambroxol at a glassy carbon electrode was carried out in the pH range 1.8 - 11.0 in aqueous solution using cyclic and differential pulse voltammetry. The compound was oxidized irreversibly at high positive potentials resulting in the formation of a chemical product at less positive potentials, which was more readily oxidized than the parent compound. In addition, a differential pulse voltammetric method was proposed for the determination of the drug in different pharmaceutical formulations, and in drug dissolution studies.

Some biologically important indolylthiohydantoin derivatives were investigated electroanalytically by voltammetric determination. Based on this study, a simple, rapid, sensitive and validated voltammetric method was developed for the determination of the indolylthiohydantoin derivatives that are readily oxidized at carbon-based electrodes. Due to the similarity between electrochemical and biological reactions it can be assumed that the oxidation mechanisms taking place at the electrode and in the body share similar principles. The oxidative behavior of the indole derivatives was studied as a function of pH at a glassy carbon electrode in different buffer media. The characteristics of the corresponding electrode reaction were discussed. The studied molecules are extensively metabolized in vivo, mainly through oxidative processes and we assume that the oxidation of the indolic compounds occurs on the nitrogen atom in the indole ring of the molecule. A linear response was obtained in the different media for all the compounds with a detection limit of 1.96 × 10−6 M, 2.32 × 10−6 M, 1.44 × 10−6 M and 7.10 × 10−7 M for compounds 1, 2, 3 and 4 respectively.

A reversed-phase high performance liquid chromatography (RP-HPLC) method with UV detection is described for the simultaneous determination of metronidazole and miconazole in pharmaceutical dosage forms. Chromatography was carried out on a Cl 8 reversed-phase column, using a mixture of methanol-water (40 + 60, v/v) as a mobile phase, at a flow rate of 1.0 ml min(-1). Sulfamethoxazole was used as an internal standard and detection was performed using a diode array detector at 254 nm. The method produced linear responses in the concentration ranges 10-70 and 1-20 mug ml(-1) with detection limits 0.33 and 0.27 mug ml(-1) for metronidazole and micanozole, respectively. This procedure was found to be convenient and reproducible for analysis of these drugs in ovule dosage forms. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

In the present study, a simple, sensitive, precise and rapid reversed-phase high performance liquid chromatographic (HPLC) method with ultraviolet detection for the simultaneous analysis of trimethoprim (TMP) and sulphamethoxazole (SPM) is developed and applied to the determination in commercial pharmaceutical preparations. These compounds are well separated on a Bondapak C(18) reverse phase column using a mobile phase consisted of a mixture of methanol:water (60:40; v/v) adjusted to pH 3 with 10% orthophosphoric acid at a flow rate of 1.8 ml min(-1). The proposed method was linear in the range 2.0-10.0 microgram ml(-1) for TMP and 10.0-50.0 microgram ml(-1) for SPM. The limit of detection were 0.45 and 1.21 microgram ml(-1) for TMP and SPM, respectively. The method which is rapid, simple and does not require any separation step, has been successfully applied to the assay of commercial tablet and oral suspension dosage forms containing TMP and SPM.

Some biologically important and melatonin-related indole-3-propionamide derivatives were synthesized. The compounds synthesized were analyzed and characterized first by NMR and mass spectrometry and then investigated by analytical voltammetric techniques. Based on this study a simple, rapid and sensitive voltammetric method was developed for the determination of the indole derivatives that are readily oxidized at the carbon-based electrodes. The oxidative behavior of the indole derivatives was studied as a function of pH at a glassy carbon electrode. The characteristics of the corresponding electrode reaction were discussed. (C) 2001 Elsevier Science S.A. All rights reserved.

A validated capillary electrophoretic method with UV detection is described for the determination of enoxacin [ENX] in pharmaceutical preparation and human serum. The experiments were carried out in a fused-silica capillary (ID=75 µm, total 88 cm, effective 58 cm length) using a 20 mM borate buffer at pH 8.6, applying a potential of 30 kV, 1 s of injection. Acetylpipedimic acid was used as an internal standard (IS) and the detection was performed at 265 nm. The tM±RSD% of ENX and IS were 4.8±0.9 and 5.5±1.2 minutes, respectively. A well-correlated calibration equation was obtained in the range of 3.1x10-6-3.1x10-5 M ENX. Limit of detection (LOD) was 3.5x10-6 M (S/N = 3). A modified reversed-phase HPLC was also conducted using a C-18 ODS column for the analysis of ENX to compare to its applicability with the CE method. An isocratic elution was performed using a mobile phase of 10 mM phosphate buffer (pH 4.0) and acetonitrile (85:15;v/v) detecting at 260 nm. The determination of ENX in the pharmaceutical tablet formulation was carried out by both methods and the results of a single tablet (as mg with their RSD% values) was found to be 421.4±1.0 and 415.9±0.9 by CE and HPLC, respectively. ENX analysis was also performed by a standard addition method in serum, and the recoveries were found to be 89.7±0.6 (CE) and 78.8+4.9 (HPLC). It was concluded that capillary electrophoresis for the determination of ENX is a promising method for routine analysis and pharmacokinetic and bioavailability studies.

The oxidation of fluvastatin sodium on a glassy carbon electrode has been studied by use of a variety of voltammetric techniques. Different conditions were investigated to optimize the determination of fluvastatin sodium. The dependence of the intensities of currents and potentials on pH, concentration, scan rate, and nature of the buffer was investigated. Oxidation of fluvastatin sodium was found to be diffusion-controlled and irreversible. The best results for the determination of fluvastatin sodium were obtained by using differential pulse and square-wave voltammetric techniques in Britton-Robinson buffer at pH 10.04. Differential pulse and square-wave voltammetry at a glassy carbon electrode resulted in linear calibration in the range 8x10(-6) to 6x10(-4) mol L(-1) and detection limits of 1.07x10(-6) and 7.99x10(-7) mol L(-1), respectively. The proposed methods were successfully applied to the determination of the drug in capsules and biological fluids. Excipients did not interfere with the determination. Statistical validation revealed that the methods were free from significant systematic errors.

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 mug ml(-1) for valsartan and 4.0-12.1 mug ml(-1) for hydrochlorothiazide. Furthermore, a highperformance liquid chromatographic procedure with ultraviolet detection at 22 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 mug m(-1), respectively. The proposed methods were successfully applied to the determination of these drugs in laboratory-prepared mixtures and commercial tablets. (C) 2001 Elsevier Science B.V. All rights reserved.

A new, simple, precise, accurate, and rapid reverse-phase high performance liquid chromatographic (RP-HPLC) method has been developed for the simultaneous determination of fosinopril sodium and hydrochlorothiazide from tablets. The procedure is based on the use of the RP-HPLC method with a UV detector. Each analysis requires no longer than 6 minutes. A reversed phase C18 column with a mobile phase composed of a mixture of methanol: water (40:60, v/v), adjusted to pH 4 with 10% orthophosphoric acid, was used to separate both compounds with sulfamethoxazole, as an internal standard, in a reasonable time period. The linearity range for fosinopril sodium and hydrochlorothiazide was 1.6–30 μg/mL and 1–30 μg/mL, respectively. The detection limits for fosinopril sodium and hydrochlorothiazide were 0.29 μg/mL and 0.26 μg/mL, respectively.

A high-performance liquid chromatographic procedure with two detectors is presented for the determination of verapamil in pharmaceutical dosage forms. The procedure is based on the use of reversed-phase high-performance liquid chromatography with UV and fluorimetric detectors. Each analysis required no longer than 6 min for both detection procedures. Quantification was achieved by measurement of the ratio of the peak area of the drug to the internal standard (fluoxetine) and the detection limit was 10 ng/ml for the UV detector and 750 pg/ml for the fluorimetric detector. There was no significant difference between inter- and intra-day studies for verapamil determined for two different concentrations (0.05 and 1.00 microgram/ml). This process could be used to determine verapamil concentrations in the range 0.025-50 and 0.0008-20 micrograms/ml for UV and fluorimetric detection, respectively. These methods were applied, without any interference from the excipients, for the determination of the drug in tablets and in drug dissolution studies. It is suggested that the proposed HPLC procedures could be used for routine quality control and dosage form assay of verapamil hydrochloride.

The oxidative voltammetric behaviour of zuclopenthixol (ZPT) at a glassy carbon has been studied using cyclic, linear sweep and differential pulse voltammetry. Oxidation of the drug produced three pH dependent anodic steps (representing an irreversible oxidation). Using differential pulse voltammetry, the drug yielded a well-defined voltammetric response in phosphate buffer, pH 5.2 atf 0.82 V (vs. Ag/AgCl). This process could be used to determine ZPT concentrations in the range 8 x 10(-7)-2 x 10(-4) M. The method was applied, without any interferences from the excipients, to the determination of the drug in tablets and oral drops, and in drug dissolution studies. (C) 2000 Elsevier Science B.V. All rights reserved.

A voltammetric study of the oxidation of terbutaline has been carried out at an activated glassy carbon electrode. The compound was oxidized irreversibly at high positive potential. The response was evaluated with respect to pH, scan rate, nature of the buffer and other variables. The peak current, at about 0.8 V (versus a saturated calomel electrode), was proportional to the terbutaline concentration in the range of 8 x 10(-6)-8 x 10(-4) M in phosphate buffer pH 6.0. This method was applied, without any interferences from the excipients, to determine the drug in a tablet dosage form. (C) 1998 Elsevier Science B.V. All rights reserved.

The electrochemical properties of nifedipine have been investigated in aqueous solution by linear sweep and cyclic voltammetry. The method is based both on the reduction and on the oxidation of the drug at a glassy carbon electrode activated by applying a new pre-treatment. The voltammograms of nifedipine on pH, concentration and scan rate have been carefully examined. Both the electroreduction and electrooxidation of nifedipine allow its determination at pH 1.5 in the concentration range of 2 x 10(-5)-6 x 10(-4) M and 8 x 10(-5)-1 x 10(-3) M, respectively. The method has been applied to commercial samples (tablets and capsules).

In this study two butyrophenones, droperidol and benperidol were voltammetrically investigated using platinum and specially activated glassy carbon electrodes. The behaviours of the substances were investigated in various electrolyte solutions having different pH values and by different scan rates. As a result of the studies it was shown that the quantitative determinations of the substances from their pharmaceutical preparations could be made rapidly and simply without any separation from the excipients.

Analytical methods including chromatographic methods are commonly used for the quantitative and qualitative analysis of raw materials, drug substances, drug products, and compounds in biological samples in pharmaceutical industry. The components monitored include chiral or achiral drugs, process impurities, residual solvents, excipients such as preservatives, degradation products, extractable and leachable from container and closure or manufacturing process, pesticide in drug product from plant origin, and metabolites. Validation of an analytical method which is used during drug development and drug manufacturing is required to demonstrate that the methods are fit for their intended purpose. Additionally, the pharmaceutical industry around the world is subject to extensive regulations due to the nature of its products. Analytical chemists play important roles in monitoring the drugs in their dosage forms and biological samples. From the viewpoints mentioned above, the title of this special issue was chosen so as to ask chemists to appreciate their great roles in chemistry science. This special issue features 8research articles. In this special issue, development of chromatographic methods such as high performance liquid chromatography, gas chromatography, micellar liquid chromatography, and their validations is presented. The purpose of this special issue will be to serve as a guide to what chromatographic methods bring to analytical and medicinal chemistry and other pharmaceutical sciences as well as briefly review their role in drugs and the new developments and validation of assay methods of pharmaceutically active compounds. Also, recent developments of application, evaluation, and validation of chromatographic methods are focused on by key topics in drug developments and analysis by assessment of the distinguished authors of this special issue. We hope that the reader will find a number of topics of interest and that additional new ideas will emerge from this special issue.

The electrochemical behaviour of fluphenazine based on its oxidation at platinum and glassy carbon electrodes was investigated by linear sweep and cyclic voltammetry. The influence of pH, concentration, nature of the buffer and scan rate was carefully examined. At both electrodes, three anodic steps (representing an irreversible oxidation) were obtained. The method was applied to the determination of fluphenazine in sugar-coated tablets.

Sibel A. Ozkan studied at Ankara University, from where she received her Pharmacy degree in 1985. She obtained her Master’s (1988) and PhD (1994) degrees in the same university, Analytical Chemistry Department. She has become full professor 2003. She has been involved in several analytical chemistry projects related to electroanalytical chemistry and separation techniques on drug active compounds and DNA-Drug interactions. She has organized and participated in organizing committees of a number of international meetings related to Pharmaceutical Sciences (Series of ISOPS-Ankara-Turkey). Her research interest focuses on the electrochemical investigations of pharmaceutically active compounds and their analysis using electroanalytical, chromatographic and spectrophotometric methods, and their validations. Her research area currently moves to the development of DNA biosensors and their interactions with drugs. She is currently a faculty member at the Analytical Chemistry Department at Faculty of Pharmacy, Ankara University.

The electrochemical oxidation of S-adenosyl-L-methionine (SAM) has been carried out in aqueous solution in the pH range 1.5–11.0 by cyclic, linear sweep, differential pulse (DPV) and square-wave (SWV)voltammetry. SAM exhibits one oxidation peak or wave depending on pH. The oxidation process was shown to be irreversible. For analytical purposes, a very well resolved diffusion controlled voltammetric peak was obtained in phosphate buffer at pH 2.04 for DPV and SWV techniques. The linear response was obtained in the ranges of 2×10−5–6×10−4 M for both techniques with a detection limit of 2.6×10−6 M for DPV and 2.4×10−6 M for SWV. Based on this study, simple, rapid and selective two voltammetric methods were developed for the determination of SAM in tablet dosage forms.

Ceftazidime (CFT) is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In this study, the copper(II) complex of CFT has been synthesized. This prepeared complex was characterized by physicochemical and spectroscopic methods. Its UV-Vis, IR and mass spectra suggest that CFT potentially acts as a bi-dentate ligand. The electrochemical behavior of this synthesized complex was studied over glassy carbon electrode in various buffer solutions using cyclic, linear sweep, differential pulse (DP) and square wave (SW) voltammetric techniques. CFT enrichment is observed over Cu(II) complex. The peak current and peak potential of the complex depend on pH, initial potential, and scan rate. DP and SW voltammetric techniques were used for the determination of CFT-Cu(II) complex. For solid synthesis complex, the linear response was within 1x10(-6) - 1x10(-4) M with a detection limit on one decimal point: 2.36x10(-7) for DPV and 1.60x10(-7) M for SWV techniques in Britton Robinson (BR) buffer at pH 8. All necessary validation parameters were investigated as detailed in all media. The complex and CFT have been screened for antibacterial activity and results were compared with the activity of the uncomplexed antibiotic against Pseudomonas aeruginosa, Kluvyeromyces fragilis, Saccharomyces cerevisiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Bacillus megaterium, Candida albicans, Mycobacterium smegmatis, Bacillus cereus, Enterococcus cloacae and Micrococcus leteus. The complex was found to be more potent against two bacterial species than the uncomplexed CFT.

In this extended special feature to celebrate the 35th anniversary edition of LCGC Europe, leading figures from the separation science community explore contemporary trends in separation science and identify possible future developments.

Amlodipine besylate (AML) is a long-acting calcium channel blocker used as an antihypertensive agent. Valsartan (VAL) is also used to treat hypertension, either alone or in combination with other agents. Two-component mixtures of AML and VAL were analyzed by HPLC and the ratio spectra of the first derivative spectrophotometric technique. The spectrophotometric method depends on the first derivative of the ratio-spectra by measurements of the amplitudes at 234.0 nm for VAL and 351.0 nm for AML. Calibration graphs were established for 0.520 g/mL AML and 132 g/mL VAL using the ratio spectra of the first derivative spectrophotometric method. In the HPLC method, an ACE 5 C18 (4.6 150 mm, 5 m) RP column at 30C with the mobile phase methanolacetonitrileNaH2PO4H2O buffer, including 5 mL/L triethylamine and adjusted to pH 3.0 (42 + 18 + 40, v/v/v) at 2.0 mL/min flow rate was used to separate both compounds with detection at 254.0 nm. Linearity was obtained in the concentration range of 0.5500 g/mL for AML and 5.0900 g/mL for VAL. The proposed methods have been extensively validated. These methods allow a number of cost- and time-saving benefits. They were successfully applied to the determination of AML and VAL in synthetic mixtures and in a pharmaceutical dosage form. There was no significant difference between the performance of the proposed methods regarding the mean and SD values. The proposed methods are simple, rapid, and suitable for QC applications.