Voltammetric studies on the potent carcinogen, 7,12-dimethylbenz[a]anthracene: Adsorptive stripping voltammetric determination in bulk aqueous forms and human urine samples and detection of DNA interaction on pencil graphite electrode.

7,12-Dimethylbenz[a]anthracene (DMBA), is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a very potent carcinogen. Initially, the electrochemical oxidation of DMBA at the glassy carbon and pencil graphite electrodes in non-aqueous media (dimethylsulphoxide with lithium perchlorate) was studied by cyclic voltammetry. DMBA was irreversibly oxidized in two steps at high positive potentials, resulting in the ill-resolved formation of a couple with a reduction and re-oxidation wave at much lower potentials. Special attention was given to the use of adsorptive stripping voltammetry together with a medium exchange procedure on disposable pencil graphite electrode in aqueous solutions over the pH range of 3.0-9.0. The response was characterized with respect to pH of the supporting electrolyte, pre-concentration time and accumulation potential. Using square-wave stripping mode, the compound yielded a well-defined voltammetric response in acetate buffer, pH 4.8 at +1.15V (vs. Ag/AgCl) (a pre-concentration step being carried out at a fixed potential of +0.60V for 360s). The process could be used to determine DMBA concentrations in the range 2-10nM, with an extremely low detection limit of 0.194nM (49.7ngL(-1)). The applicability to assay of spiked human urine samples was also illustrated. Finally, the interaction of DMBA with fish sperm double-stranded DNA based on decreasing of the oxidation signal of adenine base was studied electrochemically by using differential pulse voltammetry with a pencil graphite electrode at the surface and also in solution. The favorable signal-to-noise characteristics of biosensor resulted in low detection limit (ca. 46nM) following a 300-s interaction. These results displayed that the electrochemical DNA-based biosensor could be used for the sensitive, rapid, simple and cost effective detection of DMBA-DNA interaction.

Single-dose depot leuprolide is as efficient as daily short-acting leuprolide in ICSI cycles.

BACKGROUND: In this prospective randomized study, we aimed to compare the efficacy of a single depot (1.88 mg) reduced dose with a daily low dose (0.5 mg/day) of leuprolide for pituitary suppression as part of controlled ovarian hyperstimulation (COH) in an ICSI program. METHODS: The study population consisted of 103 patients randomized into two groups. Group 1 (n = 52) consisted of patients who had daily low-dose leuprolide injections. Group 2 (n = 51) consisted of patients who had the 1.88 mg single-dose leuprolide injection. RESULTS: The age of the patients, the number of metaphase II oocytes, the number and quality of embryos transferred were similar between the two groups. Although the length of gonadotrophin stimulation was significantly longer in group 2 (P < 0.01), the amount of gonadotrophins used was similar (P = 0.34). Leuprolide levels were significantly lower in group 2 within the first 8 h after injection (P < 0.05), but no difference was observed thereafter. Although LH levels on the day of hCG (P = 0.06) administration and estradiol levels on day 3 (P < 0.01) were lower in group 2, LH levels and progesterone levels 1 week after embryo transfer did not show any statistically significant difference. Clinical pregnancy rates per embryo transfer, implantation rates and first trimester abortion rates were also similar for both groups. CONCLUSIONS: A single reduced depot dose (1.88 mg) of leuprolide was found to be as effective as classical long multi-dose protocol for pituitary desensitization in COH for ICSI cycles.

Endometrial polyps smaller than 1.5 cm do not affect ICSI outcome.

This study aimed to determine whether the presence of endometrial polyps discovered during ovarian stimulation affects the outcomes of intracytoplasmic sperm injection (ICSI) cycles. This retrospective descriptive study was conducted in a private assisted reproductive technology unit. Medical records of ICSI cycles performed between January 2003 and December 2004 were reviewed. Patients were divided into three groups: patients with endometrial polyps discovered during ovarian stimulation (group 1, n=15), patients who underwent hysteroscopic polyp resection prior to their ICSI cycle (group 2, n=40) and patients without polyps (group 3, n=956). Main outcome measures were clinical pregnancy rates and implantation rates. Age of the patients, age of the husbands, body mass index, total amount of gonadotrophins used, length of stimulation, peak oestradiol concentrations, peak endometrial thickness and number of embryos replaced were not significantly different between the groups, nor were the pregnancy and implantation rates. Only one patient (12.5%) from the first group experienced miscarriage within 12 weeks of pregnancy. In conclusion, endometrial polyps discovered during ovarian stimulation do not negatively affect pregnancy and implantation outcomes in ICSI cycles.

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.

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.

Simultaneous determination of melatonin and pyridoxine in tablet formulations by differential pulse voltammetry.

A method has been developed for the simultaneous determination of melatonin (MT) and pyridoxine hydrochloride (PY) in pharmaceutical dosage forms by differential pulse voltammetry, based on the oxidation of both drugs at a glassy carbon electrode. Cyclic and linear scan voltammetry were used to examine the influence of pH, nature of the buffer, scan rate and concentration. The results in 0.5 M H2SO4 with 20% methanol allowed a method to be developed for the determination of MT and PY simultaneously and in the presence of each other in the ranges 2 x 10(-5)-8 x 10(-5) and 2 x 10(-5)-4 x 10(-4) M, with the detection limits of 5.86 x 10(-6) and 2.45 x 10(-6) M, respectively. The proposed method was successfully applied to the commercial tablets containing this drug combination without any interference by the excipients.

Voltammetric investigation of oxidation of zuclopenthixol and application to its determination in dosage forms and in drug dissolution studies.

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 at + 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.

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.

Determination of terbutaline based on oxidation by voltammetry.

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.

Electroanalytical study of nifedipine using activated glassy carbon electrode.

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).

Determination of ornidazole in pharmaceutical dosage forms based on reduction at an activated glassy carbon electrode.

The electrochemical reduction of ornidazole was studied at a glassy carbon electrode activated by applying a new pretreatment. The dependence of intensities of currents and potentials on pH, concentration, scan rate, nature of the solvent (aqueous media, mixed aqueous-organic systems) and surfactant was investigated. Linear calibration plots were obtained over the concentration ranges 4x10(-6)-6x10(-4) and 6x10(-6)-6x10(-4) mol l(-1) in 0.2 M H(2)SO(4) and acetate buffer (pH 4.7), respectively. The method was applied to the determination of ornidazole in different drug formulations.

Anodic voltammetry of fluphenazine at different solid electrodes.

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.

Electrochemical behavior of zopiclone.

The electrochemical properties of zopiclone, an anxiolytic and hypnotic drug, have been investigated by different techniques. The compound is reduced in two 2-electron steps in the pH range 0-12. The first step, which corresponds to the reduction of the pyrazine ring, is reversible in acidic and neutral solutions. Strong adsorption phenomena accompany the reduction process in acidic and neutral media. Zopiclone can be quantitatively measured over the entire pH range using DC polarography. However, the use of differential pulse and square-wave modes for quantitative measurements is more limited due to a slope modification in the current-concentration relationship. Adsorptive stripping voltammetry can be applied to the determination of low levels of the drug at pH 9, but only short deposition times may be used because large amounts of material accumulated under stirring conditions due to fast adsorption kinetics are rapidly released from the electrode surface. Detection limits are 1 x 10(-7)M and 2 x 10(-10)M for polarography and adsorptive stripping voltammetry, respectively. Only the first wave is of analytical interest for both techniques.

Investigation of the mechanism of the electrochemical oxidation of bamipine hydrochloride by voltammetry.

The electrochemical oxidation of bamipine hydrochloride in sulphuric acid and phosphate buffer solutions was examined using a platinum electrode. Two different reaction mechanisms for two different potential regions are proposed. It was shown that the determination of the drug by this method is feasible.