Determination of ethamsylate in pharmaceutical preparations by irreversible biamperometry

A novel flow-injection irreversible biamperometric method is described for the determination of ethamsylate. The proposed method is based on the oxidation of ethamsylate at one platinum electrode and the reduction of permanganate at another to form an irreversible biamperometric detection system. Ethamsylate can be determined over the range 1.0×10⁻⁶-1.0×10⁻⁴ mol l⁻¹ with a sample measurement frequency of 180 samples h⁻¹. The detection limit for ethamsylate is 4.0×10⁻⁷ mol l⁻¹. The stability of the proposed method is shown by a RSD of 0.52% for 11 replicate determinations of 2.0×10⁻⁵ mol l⁻¹ ethamsylate. The proposed method was applied to the determination of ethamsylate in pharmaceutical preparations.     

Diffusion layer titration of dipyrone in pharmaceuticals at a dual-band electrochemical cell

This paper describes the use of a thin-layered dual-band electrochemical cell operating at flow conditions to determine dipyrone (sodium salt of 1-phenil-2,3-dimethyl-4-methylaminomethanesulfonate-5-pyrazolone) by reaction with electrogenerated iodine. The electrolytic cell consisted of two closely spaced gold electrodes, the upper stream electrode serving as the generator electrode and the downstream electrode working as the collector electrode. A linear dynamic range from 2 to 15 μmol l⁻¹ dipyrone was obtained by using a sample volume of 100 μl, with a detection limit of 1.1 μmol l⁻¹. Standard deviation (S.D.) of 3.4% for 20 repetitive injections of a 40 μmol l⁻¹ dipyrone solution and sampling frequency of 90 h⁻¹ were achieved. The results obtained with the thin-layered dual-band electrochemical cell for dipyrone determination in three different pharmaceutical samples compared well with those found by iodimetry with coulometrically generated iodine.     

Spectrophotometric flow-injection analysis of mercury(II) in pharmaceuticals with p-nitrobenzoxosulfamate

A new, simple and rapid spectrophotometric FI method for the accurate and precise determination of Hg(II) in pharmaceutical preparations has been developed. The method is based on the measuring the decrease of absorbance intensity of p-nitrobenzoxosulfamate (NBS) due to the complexation with Hg(II). The absorption peak of the NBS, which is decreased linearly by addition of Hg(II), occurs at 430 nm in 2×10⁻⁴ mol l⁻¹ HNO₃ as a carrier solution. Optimization of chemical and FI variables has been made. A micro column consisting of several packing materials applied instead of reaction coil was also investigated. A background level of Fe(III) maintained in reagent carrier solution with NBS was found useful for sensitivity and selectivity. Under the optimized conditions, the sampling rate was over 100 h⁻¹, the calibration curve obtained were linear over the range 1-10 μg ml⁻¹, the detection limit was lower than 0.2 μg ml⁻¹ for a 20 μl injection volume, and the precision [S_r=1% at 2 μg ml⁻¹ Hg(II) (n=10)] was found quite satisfactory. Application of the method to the analysis of Hg(II) in pharmaceutical preparations resulted a good agreement between the expected and found values.     

Voltammetric determination of isoprenaline in pharmaceutical preparations using a copper(II) hexacyanoferrate(III) modified carbon paste electrode

The electroanalytical determination of isoprenaline in pharmaceutical preparations of a homemade carbon paste electrode modified with copper(II) hexacyanoferrate(III) (CuHCF) was studied by cyclic voltammetry. Several parameters were studied for the optimization of the sensor such as electrode composition, electrolytic solution, pH effect, potential scan rate and interferences in potential. The optimum conditions were found in an electrode composition (in mass) of 15% CuHCF, 60% graphite and 25% mineral oil in 0.5 mol l⁻¹ acetate buffer solution at pH 6.0. The analytical curve for isoprenaline was linear in the concentration range from 1.96×10⁻⁴ to 1.07×10⁻³ mol l⁻¹ with a detection limit of 8.0×10⁻⁵ mol l⁻¹. The relative standard deviation was 1.2% for 1.96×10⁻⁴ mol l⁻¹ isoprenaline solution (n=5). The procedure was successfully applied to the determination of isoprenaline in pharmaceutical preparations; the CuHCF modified carbon paste electrode gave comparable results to those results obtained using a UV spectrophotometric method.     

Determination of methimazole and carbimazole by flow-injection with chemiluminescence detection based on the inhibition of the Cu(II)-catalysed luminol-hydrogen peroxide reaction

This paper reports an indirect flow-injection (FI) method for the determination of the anti-hyperthyroid drugs methimazole and carbimazole in pharmaceuticals. The method was based on the inhibition that these thioimidazole drugs caused on the Cu(II)-catalysed chemiluminescence (CL) reaction between luminol and H₂O₂. The CL reaction was induced on-line and injection of the sample produced negative peaks as a result of the Cu(II) complexation by the analytes. The height of the FI peaks was proportional to the drug concentration in the sample. The linear range was 2-100 and 3-120 mg l⁻¹ for methimazole and carbimazole, respectively. The relative standard deviation was 1.9% for methimazole and 2.1% for carbimazole at the 50 mg l⁻¹ level (n=10). Common excipients present in pharmaceutical tablets were found not to interfere with the analysis. The method was applied to the determination of methimazole and carbimazole in pharmaceutical formulations with recoveries in the range 100±4%.     

Flow injection spectrophotometric method for chloride determination in natural waters using Hg(SCN)(2) immobilized in epoxy resin

A flow injection (FI) spectrophotometric method was proposed for the determination of chloride ion in natural waters. The determination of chloride was carried out by reaction with Hg(SCN)₂ immobilized in an epoxy resin bead in a solid-phase reactor (SPR) and the thiocyanate ions released were determined spectrophotometrically at 480 nm after complexing reaction with Fe(III). The analytical curve for chloride was linear in the concentration range from 5.6 × 10⁻⁵ to 2.2 × 10⁻⁴ mol l⁻¹ with a detection limit of 1.4 × 10⁻⁵ mol l⁻¹. The relative standard deviation (R.S.D.) was 2.2% for a solution containing 2.2 × 10⁻⁴ mol l⁻¹ (n = 10). The simple manifold allows a routine analytical frequency of 100 determinations per hour. The main advantage of the developed method is the 400% reduction of the Hg waste solution generated when compared to conventional methods for chloride determination based on the same spectrophotometric reaction.     

Determination of naproxen with solid substrate room temperature phosphorimetry based on an orthogonal array design

A solid substrate room temperature phosphorimetric method (SSRTP) for the determination of naproxen in pharmaceutical products was developed. The experimental conditions were optimized by a L₂₅ (5⁶) orthogonal array design (OAD) with five factors at five levels using statistical analysis. The five factors contained pH value of the sample solution, drying time (t_d) and drying temperature (T_d) of solid substrate paper in the oven, concentration (c_I⁻) of heavy atom (I⁻), and exposure time (t_e) of solid substrate paper after being dried. The pH value, t_d, c_I⁻ and t_e had significant influences on the measurement of phosphorescence intensity. The optimization for sample preparation improved greatly the analytical performance of SSRTP. Under the optimal conditions, naproxen can be determined in a linear range from 10 to 400 ng ml⁻¹ with a detection limit of 2.7 ng ml⁻¹ at 3σ. The method has been applied satisfactorily to the determination of naproxen in a commercial product.     

Cobalt phthalocyanine as a biomimetic catalyst in the amperometric quantification of dipyrone using FIA

A biomimetic sensor for the determination of dipyrone was prepared by modifying carbon paste with cobalt phthalocyanine (CoPc), and used as an amperometric detector in a flow injection analysis (FIA) system. The results of cyclic voltammetry experiments suggested that CoPc behaved as a biomimetic catalyst in the electrocatalytic oxidation of dipyrone, which involved the transfer of one electron. The optimized FIA procedure employed a flow rate of 1.5 mL min⁻¹, a 75 μL sample loop, a 0.1 mol L⁻¹ phosphate buffer carrier solution at pH 7.0 and amperometric detection at a potential of 0.3 V vs. Ag/AgCl. Under these conditions, the proposed method showed a linear response for dipyrone concentrations in the range 5.0 × 10⁻⁶-6.3 × 10⁻³ mol L⁻¹. Selectivity and interference studies were carried out in order to validate the system for use with pharmaceutical and environmental samples. In addition to being environmentally friendly, the proposed method is a sensitive and selective analytical tool for the determination of dipyrone.     

Sequential injection method for the direct spectrophotometric determination of bismuth in pharmaceutical products

A spectrophotometric method is reported for the determination of bismuth in pharmaceutical products using sequential injection analysis. Methylthymol blue (MTB) was used as a color forming reagent and the absorbance of the Bi(III)-MTB complex was monitored at 548 nm. The various chemical and physical variables that affected the reaction were studied. A linear calibration graph was obtained in the range 0.0-75.0 mg l⁻¹ Bi(III) at a sampling frequency of 72 h⁻¹. The reagent consumption was considerably reduced compared to conventional flow injection systems, as only 150 μl of MTB were consumed per run. The precision was very satisfactory (s_r=0.5%, at 50.0 mg l⁻¹ Bi(III), n=12) and the limit of detection, c_L, was 0.250 mg l⁻¹. The developed method was applied successfully to the analysis of various pharmaceutical products containing Bi(III). The relative errors e_r, were <1.5% in all cases and were evaluated by comparison of the obtained results with those found using atomic absorption spectrometry as the reference method.     

Speciation of dissolved Fe(II) and Fe(III) in environmental water samples by micro-column packed with N-benzoyl-N-phenylhydroxylamine loaded on microcrystalline naphthalene and determination by electrothermal vaporization inductively coupled plasma-optical emission spectrometry

A novel solid phase extraction technique for the speciation of trace dissolved Fe(II) and Fe(III) in environmental water samples was developed by coupling micro-column packed with N-benzoyl-N-phenylhydroxylamine (BPHA) loaded on microcrystalline naphthalene to electrothermal vaporization inductively coupled plasma-optical emission spectrometry (ETV-ICP-OES). Various influencing factors on the separation and preconcentration of Fe(II) and Fe(III), such as the acidity of the aqueous solution, sample flow rate and volume, have been investigated systematically, and the optimized operation conditions were established. At pH 3.0 Fe(III) could be selectively retained by micro-column (20 mm × 1.4 mm, i.d.) packed with BPHA immobilized on microcrystalline naphthalene, and Fe(II) passed through the micro-column. Both Fe(II) and Fe(III) could be adsorbed by the micro-column at pH 6.5. Thus, the total Fe could be determined without the need for preoxidation of Fe(II) to Fe(III). The retained Fe(III) or the Fe(II) and Fe(III) was subsequently eluted by 0.1 ml of 1 mol l⁻¹ HCl. The adsorption capacity of the solid phase adsorption material was found to be 45.0 mg g⁻¹ for Fe(III) at pH 3.0 and 65.3 mg g⁻¹ for Fe(II) at pH 6.5, respectively. The detection limit (3σ) of 0.053 μg l⁻¹ was obtained with a practical enrichment factor of 156 at a sample volume of 17 ml. The relative standard deviations of 4.2% and 4.6% (C_Fe(III) = C_Fe(II) = 10 μg l⁻¹, n = 7) for Fe(III) and total iron were found, respectively. The method was successfully applied to the determination of trace Fe(II) and Fe(III) in environmental water samples (East Lake water, local tap water and mineral water). In order to validate the method, the developed method was applied to the determination of total iron in certified materials of NIES NO.10-b rice flour and GBW07605 tea leaves, and the results obtained were in good agreement with the certified values.     

Flow analysis-hydride generation-Fourier transform infrared spectrometric determination of antimony in pharmaceuticals

In this work, a flow analysis system with hydride generation and Fourier transform infrared (FTIR) spectrometric detection has been developed for the determination of antimony in pharmaceuticals. The method is based on the on-line mineralization/oxidation of the organic antimonials present in the sample and pre-reduction of Sb(V) to Sb(III) with K₂S₂O₈ and KI, respectively; prior to the stibine generation. The gaseous SbH₃ is separated from the solution in a gas phase separator, and transported by means of a nitrogen carrier into a short pathway (10 cm) IR gas cell, where the corresponding FTIR spectrum is acquired by accumulating 3 scans in a continuous mode. The 1893 cm⁻¹ band was used for the quantification of the antimony. The procedure is carried out in a closed system, which reduces sample handling and makes possible the complete automation of the antimony determination. The figures of merit of the proposed method (linear range: 0-600 mg l⁻¹, limit of detection (3σ)=0.9 mg l⁻¹, limit of quantification (10σ)=3 mg Sb l⁻¹, precision (R.S.D.) less than 1% and sample frequency=28 h⁻¹), are appropriate for the designed application. Furthermore, precise and accurate results were found for the analysis of different antimonial pharmaceutical samples, indicating that the methodology developed represents a valid alternative for the determination of antimony in pharmaceuticals, which could be suitable for the routine control analysis.     

Sensitive determination of captopril by flow injection analysis with chemiluminescence detection based on the enhancement of the luminol reaction

This work reports a novel flow injection (FI) method for the determination of captopril, 1-[(2S)-3-mercapto-2-methylpropionyl]-l-proline (CPL), based on the enhancement CPL affords on the chemiluminescence (CL) reaction between luminol and hydrogen peroxide. For this purpose alkaline luminol and hydrogen peroxide solutions were mixed online, the sample containing CPL was injected into an aqueous carrier stream, mixed with the luminol-hydrogen peroxide stream and pumped into a glass flow cell positioned in front of a photomultiplier tube (PMT). The increase in the CL intensity was recorded in the form of FI peaks, the height of which was related to the CPL mass concentration in the sample. Different chemical and instrumental parameters affecting the CL response were investigated. Under the selected conditions, the log-log calibration curve was linear in the range 5-5000 μg l⁻¹ of CPL, the limit of detection was 2 μg l⁻¹ (at the 3σ level), the R.S.D., s_r was 3.1% at the 100 μg l⁻¹ level (n=8) and the sampling rate was 180 injections h⁻¹. The method was applied to the determination of CPL in pharmaceutical formulations with recoveries in the range 100±3%.     

Flow injection spectrophotometric determination of fosfestrol, following on-line thermal induced digestion and using an orthophosphate calibration graph

A novel flow injection (FI) system for the spectrophotometric determination of diethyl stilbestrol diphosphate (fosfestrol) in pharmaceutical formulations is described. On-line thermal induced digestion of the analyte by peroxodisulfate ion was performed and the orthophosphate ion generated was determined spectrophotometrically (λ_max=690 nm) using a molybdenum blue based FI approach. As the achieved conversion of the analyte was quantitative, an orthophosphate calibration graph can be used for its determination as well. The chemical and FI variables affecting the digestion were investigated. A linear calibration graph was obtained in the range 5.0×10⁻⁷-1.0×10⁻⁴ mol l⁻¹ fosfestrol. The relative standard deviation was very good (s_r=0.8% at 5.0×10⁻⁵ mol l⁻¹ fosfestrol, n=12) and the 3σ detection limit was 2.5×10⁻⁷ mol l⁻¹. The sampling rate was 60 injections h⁻¹. The average accuracies for the determination of the analyte in a pharmaceutical formulation evaluated by comparison of the results with those obtained by the supplier (Asta Medica) and the method recommended by the US Pharmacopoeia were also very good (e_r of +0.8 and −0.3%, respectively). Average recoveries of known amounts of the analyte ranging between 97.9 and 100.8% were also obtained.     

Sensitive sequential injection determination of naproxen based on interaction with beta-cyclodextrin

A sensitive sequential injection analysis (SIA) methodology for the fluorimetric determination of naproxen is proposed. The developed automatic analytical procedure is based on the complexation of naproxen with β-cyclodextrin (β-CD) yielding an enhanced fluorimetric signal (λ_ex = 280 nm, λ_em = 356 nm).Linear calibration plots were obtained for naproxen concentrations up to 1 × 10⁻⁵ mol l⁻¹. The developed methodology exhibited a good precision, with a R.S.D. < 2.1% (n = 15). The detection limit of the determination was 1.9 × 10⁻⁷ mol l⁻¹ with a sampling rate of about 70 h⁻¹. The automatic method was applied to the determination of naproxen in pharmaceutical formulations. The obtained results were compared with those furnished by the reference procedure and the relative deviations were lower than 3.6%. No interference was found from the excipients usually used in solid pharmaceutical formulations.     

Rapid spectrophotometric determination of fosfestrol following on-line hydrolysis by alkaline phosphatase using flow injection and chasing zones

A new flow injection (FI) method is reported for the spectrophotometric determination of fosfestrol (diethyl-stilbestrol (DES) diphosphate) in pharmaceutical formulations. The proposed method is based on the on-line hydrolysis of the analyte by alkaline phosphatase (Al-Pase) using a “chasing zones” FI manifold. The orthophosphate ions, thus, generated are determined spectrophotometrically (λ_max=690 nm) using the molybdenum blue approach. The chemical and FI variables affecting the enzymatic reaction were investigated. The proposed method is very precise (s_r=1.1% at 1×10⁻⁴ mol l⁻¹ fosfestrol, n=12), fast (allowing up to 40 samples h⁻¹ to be analyzed) and has a determination range of 2×10⁻⁵ to 2×10⁻⁴ mol l⁻¹, with a satisfactory 3σ detection limit of 5×10⁻⁶ mol l⁻¹. The method was shown to provide accurate determinations of the fosfestrol concentration in a pharmaceutical formulation, giving relative errors, e_r, of +0.6 and −0.5% compared to the value stated by the supplier (Asta Medica Inc.) and the concentration derived using a method recommended by the United States Pharmacopoeia XXI, respectively. In addition, the average recoveries of known amounts of the analyte ranged between 99.2 and 101.2%.     

Solid substrate-room temperature phosphorimetry for the determination of residual clenbuterol hydrochloride based on the catalysis of sodium periodate oxidizing eosine Y

Clenbuterol hydrochloride (CLB) could catalyze NaIO₄ oxidation of eosine Y (R), which caused the room temperature phosphorescence (RTP) signal of R to quench sharply. The ΔI_P (=I_P2 − I_P1, I_P2 was RTP intensities of reagent blank and I_P1 was RTP intensities of test solution) of the system was directly proportional to the content of CLB. According to that academic thought, a new solid substrate-room temperature phosphorimetry (SS-RTP) for the determination of trace CLB has been established. This method has high sensitivity (detection limit (LD): 0.021 zg spot⁻¹, corresponding concentration: 5.2 × 10⁻²⁰ g mL⁻¹) and good selectivity (Er = ±5%, interfering species were of no interference). It has been applied to the determination of residual CLB in the practical samples. The results were verified using HPLC and GC/MS methods. The reaction mechanism of catalytic SS-RTP for the determination of residual CLB was also discussed.     

Determination of As(III) and As(V) in soils using sequential extraction combined with flow injection hydride generation atomic fluorescence detection

An analytical procedure for determination of As(III) and As(V) in soils using sequential extraction combined with flow injection (FI) hydride generation atomic fluorescence spectrometry (HG-AFS) was presented. The soils were sequentially extracted by water, 0.6 mol l⁻¹ KH₂PO₄ solution, 1% (v/v) HCl solution and 1% (w/v) NaOH solution. The arsenite (As(III)) in extract was analyzed by HG-AFS in the medium of 0.1 mol l⁻¹ citric acid solution, then the total arsenic in extract was determined by HG-AFS using on-line reduction of arsenate with l-cysteine. The concentration of arsenate (As(V)) was calculated by the difference. The optimum conditions of extraction and determination were studied in detail. The detection limit (3σ) for As(III) and As(V) were 0.11 and 0.07 μg l⁻¹, respectively. The relative standard deviation (R.S.D.) was 1.43% (n=11) at the 10 μg l⁻¹ As level. The method was applied in the determination of As(III) and As(V) of real soils and the recoveries of As(III) and As(V) were in the range of 89.3-118 and 80.4-111%, respectively.     

Analytical strategy photodegradation/chemiluminescence/continuous-flow multicommutation methodology for the determination of the herbicide Propanil

The present paper is dealing with an analytical strategy based on coupling photodegradation, chemiluminescence and multicommutation continuous-flow methodology for the determination of the pesticide Propanil, a common herbicide. The pesticide solution is inserted as small segments sequentially alternated with segments of the solution for adjusting the suitable medium for the photodegradation. Both flow-rates (sample and medium) are adjusted to required time for photodegradation, 2.0 min; and then, the resulting solution is also sequentially inserted as segments alternated with segments of the oxidizing solutions system, 1.00 × 10⁻⁴ mol l⁻¹ potassium permanganate in 2.00 mol l⁻¹ sulphuric acid medium. The calibration range, from 10 μg l⁻¹ to 25 mg l⁻¹, resulted in a linear behaviour over the range 10 μg l⁻¹-5 mg l⁻¹ and fitting the linear equation: I = 780.30C + 95.28; correlation coefficient 0.9999. The limit of detection was 8 μg l⁻¹ and the sample throughput 20 h⁻¹. After testing the influence of a large series of potential interferents the method is applied to water samples obtained from different places and to one formulation. The method is valid for the determination of other pesticides from the same chemical family, namely: alachlor, flumetsulam, furalaxyl and ofurace. Calibration graphs, limits of detection, repeatability and determination in water samples are obtained for each reported pesticide.     

Determination of adrenaline by using inhibited Ru(bpy)3 electrochemiluminescence

Adrenaline was found to inhibit strongly the electrochemiluminescence (ECL) from the Ru(bpy)₃²⁺/tripropylamine system when a working Pt electrode was maintained at 1.05 V (versus Ag/AgCl) in pH 8.0 phosphate buffer. On this basis, a flow injection (FI) procedure with inhibited electrochemiluminescence detection has been developed for determination of adrenaline. The method exhibited a good reproducibility, sensitivity, and stability with a detection limit (signal-to-noise ratio = 3) of 7.0×10⁻⁹ mol l⁻¹ and dynamic concentration range of 2×10⁻⁸ to 1×10⁻⁴ mol l⁻¹. The relative standard deviation was 2.2% for 1.0×10⁻⁶ mol l⁻¹ adrenaline (n=11). The method was successfully applied to the determination of adrenaline in pharmaceutical samples. Moreover, ECL emission spectra, UV-Vis absorption spectra and cyclic voltammograms of Ru(bpy)₃²⁺/tripropylamine/adrenaline were studied. The inhibition mechanism has been proposed as the interaction of electrogenerated Ru(bpy)₃^2+* and the o-benzoquinone derivatives, adrenochrome and adrenalinequinone, at the electrode surface.