Electrochemical determination of prolintane in pharmaceutical formulations and in human urine

The oxidative behavior of 1-[1-(phenylmethyl)butyl]pyrrolidine, prolintane, was studied at a glassy carbon electrode using linear-sweep and differential-pulse voltammetry. The oxidation process was shown to be irreversible using 0.04 M Britton–Robinson buffer and was diffusion-adsorption controlled. Two voltammetric methods were developed for the determination of prolintane using different techniques: linear-sweep and differential-pulse voltammetry. The peak current varied linearly with prolintane concentrations in the range of 1.0 × 10⁻⁵ −2.5 × 10⁻⁴ M, with a detection limit of 8.5 × 10⁻⁶ and 4.0 × 10⁻⁶ M, and with relative standard deviations of 2.1 % and 3.1 %, respectively. The methods were applied to commercial preparations, giving relative errors less than 3.1 % and relative standard deviations lower than 4.8 % (n = 10). Determination of prolintane (down to the 8.5 × 10⁻⁸ M level) can be performed by using a preconcentration step prior to the determination by differential-pulse voltammetry in 0.04 M Britton–Robinson buffer (pH 8.0) with preconcentration potential of 0.0 V. The detection limit was found to be 6.2 × 10⁻⁸ M (4 min preconcentration) and the relative standard deviation for 2.5 × 10⁻⁷ M prolintane (n = 5) was 4.6 %. Applicability to human urine analysis is illustrated (recovery 98 ± 2 %). Standard additions method can be used to determine prolintane in real samples of urine.     

Voltammetric determination of coenzyme Q10 in pharmaceutical dosage forms

A simple and rapid voltammetric method has been developed for the quantitative determination of coenzyme Q(10) (CoQ(10)) in pharmaceutical preparations. Studies with differential pulse voltammetry (DPV) were carried out using a glassy carbon electrode (GCE) in a mixed solvent containing 80 vol.% acetic acid and 20 vol.% acetonitrile. A well-defined reduction peak of CoQ(10) was obtained at -20 mV vs. Ag/AgCl. The voltammetric technique applied provides a precise determination of CoQ(10) using the multiple standard addition method. The statistical parameters and the recovery study data clearly indicate good reproducibility and accuracy of the method. The accuracy of the results assessed by recovery trials was observed to be within the range of 101.1% to 102.5%. The detection and quantification limits were found to be 0.014 mM (12 mg L(-1)) and 0.046 mM (40 mg L(-1)), respectively. An analysis of real samples containing CoQ(10) showed no interferences with common additives and excipients, such as unsaturated fatty acids and soya lecithin. The method proposed does not require any pretreatment of the pharmaceutical dosage forms. A spectrophotometric determination of CoQ(10) in real samples diluted in mixtures containing ethanol and n-hexane was also performed for comparison.     

Gas chromatographic determination of parabens in various pharmaceutical dosage forms

Summary A specific, sensitive and general applicabla gas chromatographic method is described for the determination of parabens in various liquid pharmaceutical preparations: propylparaben and butylparaben in a liquid antacid dosage form (I); methylparaben, ethylparaben and propylparaben in a syrup (II); methylparaben and propylparaben in a solution for injection (III). Each time one of the parabens is used as internal standard. The parabens are extracted with diethylether and derivatized by silylation. Different columns are used for the analysis of the parabens: 3% SE-30 column, a 3% QF-1 column for different selectivity, a 2% OV-1 column for isothermal operation.Special attention is attributed to the standard: the parabens are dissolved in a minimal amount of 0.1 M sodium hydroxide and extracted in the same way as the pharmaceutical dosage form.     

Electrochemical reduction of nicergoline and its analytical determination in dosage forms

Electrochemical reduction of nicergoline was studied at different pH and concentrations using differential pulse polarography and linear sweep voltammetry. Both techniques reveal that the reduction process occurs with strong adsorption of the product. Nicergoline is an excellent model for the previously developed theory related to the effects of strong adsorption of electroactive species in voltammetry. At concentrations below 0.1 mM, the adsorption prepeak is linearly dependent on nicergoline concentration. This peak was used to develop a new differential pulse polarographic method for the determination of the drug in pharmaceutical dosage forms. The method is simple and not time-consuming because nitrogen purging of samples and previous separation of the excipients were not needed. A comparative UV spectrophotometric assay was applied. Recovery data and composite and uniformity content studies for both methods are reported.     

Spectrophotometric determination of metronidazole in pharmaceutical pure and dosage forms using p-benzoquinone

A simple and accurate spectrophotometric method for the determination of metronidazole in pure and pharmaceutical dosage forms has been developed. The proposed method is based on the reduction of the nitro group to amino group of the drug. This can be achieved by heating a mixture of an alcoholic solution of metronidazole, zinc powder and dilute hydrochloric acid in a water bath at 90 ± 5 °C for 15 min. The cold and clear filtrate reacts with p-benzoquinone to develop a purple color, which absorbs maximally at 526 nm. The calibration graph is linear over the concentration range of 15–190 μg ml^?1 with a molar absorptivity of 1.09 × 10³ l mol^?1 cm^?1. The proposed method is applied to commercially available pharmaceutical dosage forms and the results are statistically compared with those obtained by the reference method.     

Spectrophotometric determination of tranexamic acid in pharmaceutical bulk and dosage forms.

In this study, a simple, fast, accurate and sensitive spectrophotometric method has been developed for the determination of tranexamic acid in bulk and pharmaceutical preparations. The method is based on the reaction of ninhydrin with the primary amino group of tranexamic acid in the basic medium at pH 8.0. The reaction produces a bluish-purple color which absorbs maximally at 565 nm. Beer's law was obeyed in the range of 3-40 microg ml(-1) with molar absorptivity of 5.093 x 10(3) L mol(-1) cm(-1). The effects of various factors such as temperature, heating time, concentration of reagent, color stability and interferences were investigated to optimize the procedure. The results have been validated analytically and statistically. The proposed method has been applied for the determination of tranexamic acid in bulk and pharmaceutical preparations with good results.     

Fluorimetric determination of mebendazole and flubendazole in pharmaceutical dosage forms after alkaline hydrolysis

The selective and very sensitive fluorimetric determination of mebendazole and flubendazole is based on alkaline hydrolysis and adsorption on Whatman 42 filter paper. Limits of detection are 0.1 μg ml^?1 and 0.5 μg ml^?1, respectively, with linear response sponse up to 10 μg ml^?1 and 50 μg ml^t?1. The fluorescence produced is very stable (λ_em = 460 nm) and the method is applicable to anthelmintic pharmaceutical preparations.     

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 × 10⁻⁶-2 × 10⁻⁴ M range in supporting electrolyte and spiked serum sample; 8 × 10⁻⁶-2 × 10⁻⁴ M range in urine sample; 6 × 10⁻⁶-1 × 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.     

Spectrophotometric determination of certain CNS stimulants in dosage forms and spiked human urine via derivatization with 2,4-Dinitrofluorobenzene

A new spectrophotometric method is developed for the determination of phenylpropanolamine HCl (PPA), ephedrine HCl (EPH) and pseudoephedrine HCl (PSE) in pharmaceutical preparations and spiked human urine. The method involved heat-catalyzed derivatization of the three drugs with 2,4-dinitrofluorobenzene (DNFB) producing a yellow colored product peaking at 370 nm for PPA and 380 nm for EPH and PSE, respectively. The absorbance concentration plots were rectilinear over the range of 2-20 for PPA and 1-14 μg/mL for both of EPH and PSE, respectively. The limit of detection (LOD) values were 0.20, 0.13 and 0.20 μg/mL for PPA, EPH and PSE, respectively and limit of quantitation (LOQ) values of 0.60 and 0.40 and 0.59 μg/mL for PPA, EPH and PSE, respectively. The analytical performance of the method was fully validated and the results were satisfactory. The proposed method was successfully applied to the determination of the three studied drugs in their commercial dosage forms including tablets, capsules and ampoules with good percentage recoveries. The proposed method was further applied for the determination of PSE in spiked human urine with a mean percentage recovery of 108.17 ± 1.60 for (n = 3). Statistical comparison of the results obtained with those of the comparison methods showed good agreement and proved that there was no significant difference in the accuracy and precision between the two methods. The mechanism of the reaction pathway was postulated.     

Anodic voltammetric behavior of resveratrol and its electroanalytical determination in pharmaceutical dosage form and urine

The anodic voltammetric behavior of resveratrol was studied using cyclic and square wave voltammetric techniques. The oxidation of resveratrol is irreversible and exhibits an adsorption controlled process which is of pH dependence. The oxidation mechanism was proposed in this work. The dependence of the current on pH, the concentration and nature of buffer, and scan rate was investigated to optimize the experimental conditions for the determination of resveratrol. It was found that the optimum buffer for the determination of resveratrol is 1.0 × 10⁻³ M KCl + 0.1 M HNO₃ solution with the pH of 1.0. In the range of 5.00 × 10⁻⁹ to 1.65 × 10⁻⁷ M, the current measured by square wave voltammetry presents a good linear property as a function of the concentration of resveratrol. In addition, the reproducibility, precision and accuracy of the method were checked as well. The method was applied for the determination of resveratrol in Chinese patent medicine and diluted urine.     

Chemometrics-assisted simultaneous determination of atenolol and chlorthalidone in synthetic binary mixtures and pharmaceutical dosage forms

Resolution of binary mixtures of atenolol (ATE) and chlorthalidone (CTD) with minimum sample pre-treatment and without analyte separation has been successfully achieved, using a new and rapid method based on partial least squares (PLS1) analysis of UV spectral data. The simultaneous determination of both analytes was possible by PLS1 processing of sample absorbances between 255 and 300 nm for ATE and evaluation of absorbances in the 253–268 nm region for CTD. The mean recoveries for synthetic samples were 100.3±1.0% and 100.7±0.7% for ATE and CTD, respectively. Application of the proposed method to two commercial tablet preparations in the content uniformity test showed them to contain 103.5±0.8% and 104.9±1.8% ATE respectively, as well as 103.4±1.2% and 104.5±2.2% CTD. Use of this method also allowed the elaboration of dissolution profiles of the drugs in two commercial combined formulation products, through the simultaneous determination of both drugs during the dissolution test. At the dissolution time of 45 min specified by USP XXIV, both pharmaceutical formulations complied with the test.     

Validation of a liquid chromatographic method for determination of tacrolimus in pharmaceutical dosage forms

An accurate, simple, and reproducible liquid chromatographic method was developed and validated for the determination of tacrolimus in capsules. The analysis is performed at room temperature on a reversed-phase C18 column with UV detection at 210 nm. The mobile phase is methanol-water (90 + 10) at a constant flow rate of 0.8 mL/min. The method was validated in terms of linearity, precision, accuracy, and specificity by forced decomposition of tacrolimus, using acid, base, water, hydrogen peroxide, heat, and light. The response was linear in the range of 0.09-0.24 mg/mL (r2 = 0.9997). The relative standard deviation values for intra- and interday precision studies were 1.28 and 2.91%, respectively. Recoveries ranged from 98.06 to 102.52%.     

Optimization of two flow-injection spectrophotometric methods for the determination of indapamide in pharmaceutical dosage forms

Multivariate experimental design has been used to optimize 2 flow-injection spectrophotometric methods for the determination of indapamide in pharmaceutical dosage forms, both pure and commercial tablets. The methods are based on the oxidation of this drug with iron (III) in acidic medium and the subsequent formation of an intensive orange-red complex between the liberated iron (II) and 2,2'-bipyridyl or 1,10-phenanthroline reagents. Plackett-Burman designs were applied as a screening method to evaluate the most significant factors with few experiments. Central composite 2(3)+ star designs were performed to evaluate the response surfaces. The methods have been fully validated and were applied successfully to the determination of indapamide in pure and pharmaceutical forms with good accuracy and precision. Therefore, the 2 proposed procedures are simple, inexpensive, and rapid flow methods for the routine determination of indapamide in pharmaceutical preparations.     

Flow-injection determination of phenylephrine hydrochloride in pharmaceutical dosage forms with on-line solid-phase extraction and spectrophotometric detection

A flow injection method is proposed for the determination of phenylephrine hydrochloride in pharmaceutical dosage forms. The method involves the use of on-line solid-phase extraction by means of a microcolumn containing Dowex 50W X8 ion-exchange resin for the separation of the analyte prior to colour development and spectrophotometric detection in the visible region.

The influence of preconcentration flow, preconcentration pH and elution volume was studied.

The method exhibits appropriate linearity (r² = 0.9999) which was proved statistically by means of the “F”-test. When applied to commercial samples containing several active ingredients and excipients, a significant reduction of interferences was found. Accuracy, evaluated by means of the spike recovery method was in the range 99.7–100.8%, with precision (R.S.D., %) better than 1%.

In order to achieve the automation the system was controlled from a notebook computer by means of a program written in QuickBASIC language. Under these conditions, a sampling frequency of 40 samples per hour could be attained.     

Electrochemical investigation of redox reactions of herbal drug-shikonin and its determination in pharmaceutical preparations

The electrochemical behaviour of the anticancer herbal drug shikonin was investigated at glassy carbon electrode in 0.16 M HAc-NaAc (20% ethanol, pH 3.98) buffer solution using cyclic voltammetry, square-wave voltammetry and chronocoulometry. Shikonin gives a pair of quasi-reversible redox peaks at potentials of E _pc = 0.698 V and E _pa =0.632 V by absorption-controlled process at a scan rate of 100 mV/s. The electrode process dynamics parameters (saturated adsorptive amount Γ, charge transfer coefficient α, and apparent rate constant K _s) and reaction mechanism were also investigated with result of two electrons and two hydrogen ions participating in electrode reaction. The experimental conditions were optimized for the determination of shikonin and the square-wave anodic peak currents were linearly related to the shikonin concentrations in the range from 2.08 × 10⁻⁸ to 1.82 × 10⁻⁶ M with correlation coefficient of 0.998 and detection limit of 7.8 × 10⁻⁹ M. Using the established method without pretreatment and pre-separation, shikonin in herbal drug Gromwell Root was determined with satisfactory result.     

Stability-indicating high-performance liquid chromatographic assay for the determination of metoclopramide hydrochloride in pharmaceutical dosage forms

A simple, reliable and selective high-performance liquid chromatographic method for the determination of metoclopramide hydrochloride in pharmaceutical dosage forms has been developed and evaluated. The drug and the internal standard (phenobarbitone) were eluted from a 5-micron C8 reversed-phase column at ambient temperature with a mobile phase consisting of phosphate buffer (10 mM)-methanol-acetonitrile (50 + 28 + 22) adjusted to pH 4.8 with orthophosphoric acid. The mobile phase was pumped at a flow-rate of 1.5 ml min-1 and the effluent was monitored spectrophotometrically at 214 nm. The retention times of the internal standard and metoclopramide hydrochloride were 3.0 and 7.5 min, respectively. Quantification was achieved by measuring the peak-height ratio of the drug to the internal standard. A linear relationship was found over the range 1-10 micrograms ml-1. Within-day coefficients of variation (CVs) ranged from 0.50 to 1.70% and between-day CVs from 0.68 to 4.07% at three different concentrations. The developed procedure was compared with the current BP method for the assay of metoclopramide hydrochloride in tablets. The proposed method was also used to study the stability of metoclopramide hydrochloride.