Sequential injection technique for automated titration: spectrophotometric assay of vitamin C in pharmaceutical products using cerium(IV) in sulfuric acid

For the first time sequential injection analysis (SIA) technique has been employed for titrimetry. A new SI titrimetric spectrophotometric method for the assay of vitamin C in drug formulations was explored. The method is based on the oxidation reaction of vitamin C with cerium(IV) in sulfuric acid media using a spectrophotometer as a detector with the wavelength monitored at 410 nm. A 2(3) factorial design chemometric approach was employed to study the interaction effect of the chemical and system variables, mainly cerium(IV), sulfuric acid concentrations and the flow rate. The results of the chemometric optimization revealed that the optimum operating conditions for the SI titrimetric analysis of vitamin C were 7.0 x 10(-3) M cerium(IV), 0.455 M sulfuric acid and 28.9 microL s-1 flow rate. A linear calibration plot for the determination of vitamin C was obtained in the concentration range between 30 to 200 ppm. The method was applied to the determination of vitamin C in pharmaceutical preparations and no excipient was found to pose any interference, thus rendering the method suitable for the determination of the drug in pharmaceutical preparations. The SIA method is found to be accurate when the results were statistically compared with the results obtained by the BP standard method. The SIA method is superior when compared to the conventional titration method, the BP standard method and previous methods with respect to precision and automation in solution handling.     

Kinetics and mechanism of naringenin reaction with Ce(IV) in different aqueous solutions of dimethylsulfoxide

The reaction of naringenin with Ce(IV) was studied in different aqueous solutions of DMSO (50–80% v/v) and various sulfuric acid concentrations using a spectrophotometric method. The reaction was arranged to be under pseudo‐first‐order condition with respect to Ce(IV). It was found that 1 mol of Ce(IV)sulfate on average has consumed by about 2 mol of naringenin to complete the reaction. To determine the stoichiometric ratios of metal ion and the ligand in the formed complex species, the continuous variation method has been used. The results showed that pseudo‐first‐order rate constants increase with increasing naringenin concentration and decrease by increasing the amount of DMSO and sulfuric acid in solution. The rate constant (k₁) was measured at different conditions. Finally, a mechanism consistent with the observed results has been proposed and discussed at various aqueous DMSO solutions. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 715–724, 2011     

Oxidative polymerization of acrylamide in the presence of thioglycolic acid

Chemical polymerization of acrylamide at room temperature was examined by using thioglycolic acid-cerium (IV) sulfate and thioglycolic acid-KMnO₄ redox systems in acid aqueous medium. Water soluble polyacrylamides containing thioglycolic acid end groups were synthesized. The effects of the molar ratio of acrylamide to Ce(IV) n _AAm /n _Ce(IV) , the polymerization time, the temperature, the monomer concentration, the molar ratio of cerium (IV) sulfate to thioglycolic acid and the concentration of sulfuric acid on the yield and molecular weight of polymer were investigated. Lower molar ratios of acrylamide/Ce(IV) at constant monomer concentration resulted in an increase in the yield but a decrease in molecular weight of polymer. The increase of reaction temperature from 20 to 70°C resulted in a decrease in the yield but generally resulted in a constant value for the molecular weight of polymer. With increasing polymerization time, the yield and molecular weight of polymer did not change substantially. Ce(IV) and Mn(VII) ions are reduced to Ce(III) and Mn(II) ions respectively in the polymerization reaction. The existence of Ce(III) ion bound to polymer was investigated by UV-visible spectrophotometry and fluoresce measurements. The amount of Mn(II) incorporated into the polymer was determined using graphite furnace atomic absorption spectrometry. The mechanism of this phenomenon is discussed.     

Kinetic Spectrofluorometric Determination of Thioctic Acid in Bulk and Pharmaceutical Preparations via its Oxidation with Cerium(IV)

A highly simple and sensitive kinetic spectrofluorometric method was developed for the determination of thioctic acid. The method is based on the oxidation of the studied drug with cerium(IV) ammonium sulfate in acidic medium. The fluorescence of the produced Ce(III) was measured at 365 nm after excitation at 255 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The method is applicable over the concentration range of 0.02 to 0.12 μg/mL with a detection limit of 6.06 × 10^?3 μg/mL and a quantification limit of 0.02 μg/mL. The method was successfully applied for the assay of the studied drug in pharmaceutical formulations. The results obtained were in good agreement with those obtained with the reference method.     

间接荧光检测离子色谱法分析维生素C、亚硫酸根和硫代硫酸根

报道了一种用离子色谱分析维生素Ｃ、亚硫酸根和硫代硫酸根离子的新方法。在这种方法中采用了四价铈柱后氧化还原反应和三价铈荧光检测法。同时也给出了使用这种方法的一些最佳的实验条件。     

Ruthenium(III)‐mediated oxidation of D‐mannitol by cerium(IV) in aqueous sulfuric acid medium: A kinetic and mechanistic approach

The oxidation of D ‐mannitol by cerium(IV) has been studied spectrophotometrically in aqueous sulfuric acid medium at 25°C at constant ionic strength of 1.60 mol dm^?3. A microamount of ruthenium(III) (10^?6 mol dm^?3) is sufficient to enhance the slow reaction between D ‐mannitol and cerium(IV). The oxidation products were identified by spot test, IR and GC‐MS spectra. The stoichiometry is 1:4, i.e., [D ‐mannitol]: [Ce(IV)] = 1:4. The reaction is first order in both cerium(IV) and ruthenium(III) concentrations. The order with respect to D ‐mannitol concentration varies from first order to zero order as the D ‐mannitol concentration increases. Increase in the sulfuric acid concentration decreases the reaction rate. The added sulfate and bisulfate decreases the rate of reaction. The active species of oxidant and catalyst are Ce(SO₄)₂ and [Ru(H₂O)₆]³⁺, respectively. A possible mechanism is proposed. The activation parameters are determined with respect to a slow step and reaction constants involved have been determined. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 440–452, 2010     

Fluorometric determination of diphenhydramine by flow-injection analysis

A sensitive, rapid and simple flow injection procedure for the determination of diphenhydramine has been designed based on a fluorometric approach. An aqueous solution of diphenhydramine is injected into a carrierreagent stream containing Ce(IV) in dilute sulphuric acid and the fluorescence intensity of the Ce(III) produced is monitored. Chemical, FIA and instrumental variables were optimized. Analytical features of the method are: linear range 0.2–2 ppm, precision 0.7%, sample throughput 80/h. The influence of some foreign substances which can be found in typical pharmaceutical samples containing diphenhydramine was also investigated. The diphenhydramine content of a pharmaceutical preparation was determined.     

Determination of total antioxidant capacity by a new spectrophotometric method based on Ce(IV) reducing capacity measurement

Dietary antioxidants widely found in fruits and vegetables may serve the task of reducing oxidative damage in humans induced by free radicals and reactive oxygen species under ‘oxidative stress’ conditions. The aim of this work is to develop a simple, low-cost, sensitive, and diversely applicable indirect spectrophotometric method for the determination of total antioxidant capacity of several plants. The method is based on the oxidation of antioxidants with cerium(IV) sulfate in dilute sulfuric acid at room temperature. The Ce(IV) reducing capacity of the sample is measured under carefully adjusted conditions of oxidant concentration and pH such that only antioxidants and not other organic compounds would be oxidized. The spectrophotometric determination of the remaining Ce(IV) was performed after completion of reaction with antioxidants. Quercetin and gallic acid were used as standards for flavonoids and phenolic acids, respectively, and results of antioxidant measurements were reported as trolox equivalents. The developed procedure was successfully applied to the assay of total antioxidant capacity due to simple compounds such as trolox, quercetin, gallic acid, ascorbic acid, catechin, naringin, naringenin, caffeic acid, chlorogenic acid, ferulic acid, and p-coumaric acid, and due to phenolic acids and flavonoids in the arieal parts of nettle (Urtica Dioica L.). Blank correction of significantly absorbing plant extracts at 320 nm could be made with the aid of spectrophotometric titration. Plant selection was made in respect to high antioxidant content, and extraction was made with water. The proposed method was reproducible, and the trolox equivalent antioxidant capacities (TEAC coefficients) of the tested antioxidant compounds were correlated to those found by reference methods such as ABTS and CUPRAC. Since the TEAC coefficients found with the proposed method of naringin-naringenin and rutin-catechin pairs were close to each other, this Ce(IV)-based assay probably caused the simultaneous hydrolysis of flavonoid glycosides to the corresponding aglycones and their subsequent oxidation such that the hydrolysis products exhibed antioxidant capacities roughly proportional the number of -OH groups contained in a molecule.     

Electron spin resonance for quantitative assay of chlorpromazine in drug formulations by oxidation with cerium(IV) in sulfuric acid media

For the first time electron spin resonance (ESR) spectroscopic technique has been used for a highly selective determination of chlorpromazine. The method is based on the oxidation reaction of chlorpromazine with cerium(IV) in sulfuric acid media. In this method 3.8x10(-3) mol dm(-3) cerium(IV) was used in 0.035 mol dm(-3) sulfuric acid with the ESR spectra recorded at room temperature. A calibration equation of the following form was obtained over the linear concentration range of 10-100 ppm with a correlation coefficient (r) of 0.999: A=1.355+0.0382C. The results obtained by the ESR method were found to be comparable with those obtained by the British Pharmacopoeia (BP) method. The method suffers no interferences excipients rendering the method suitable for determination of this drug in pharmaceutical preparations.     

Differential electrolytic potentiometry, a detector in flow injection analysis for oxidation-reduction reactions

For the first time, differential electropotentiometry (DEP) is coupled with the flow injection analysis (FIA) technique for detection of oxidation–reduction reactions, and is utilized for quantitative determination of vitamin C in pharmaceutical preparations using 1.0×10⁻³-M cerium(IV) in 0.50-M sulfuric acid as carrier. Two similar platinum electrodes were employed and polarized by a constant current. Optimization by the univariate method was carried out and the optimum conditions for current density, flow rate, sample size and concentration of sulfuric acid were 4 mA, 0.93 ml min⁻¹, 140 μl and 0.25 M, respectively. Vitamin C was determined in the concentration range 100–300 ppm with 0.9987 correlation coefficient and 1.9 standard deviation. The method was applied to the determination of vitamin C in pharmaceutical preparations and no excipient was found to pose any interference thus rendering the method suitable for determination of the drug in pharmaceutical preparations. The accuracy of the method was determined by comparison with the BP standard method.     

Oxidation of butane-1,3-, butane-1,4-, 2-methyl pentane-2,4- and 3-methyl pentane-2,4-diols by cerium(IV) in aqueous acidic medium catalyzed by rhodium(III)

The oxidation kinetics of butane-1,3-diol, butane-1,4-diol, 2-methyl pentane-2,4-diol and 3-methyl pentane-2,4-diol with cerium(IV) catalyzed by rhodium(III) in aqueous sulfuric acid showed a peculiar nature with respect to the variation in oxidant concentration, such that the reaction follows first-order kinetics in [Ce(IV)] at low [Ce(IV)] and then reaches a maximum with increasing [Ce(IV)], beyond which further increase in the oxidant concentration retards the rate. The rate shows direct proportionality with respect to [diol] at low concentrations, becoming independent of [diol] at higher concentrations. The rate is first order in catalyst. Retarding effects are observed when [H⁺] and [Ce(III)] are increased, while [Cl⁻] and hence ionic strength have a positive effect on the rate. Spectroscopic studies confirmed that the primary hydroxyl groups in butane-1,3-diol and butane-1,4-diol resulted in the formation of 3-hydroxy butanal and 4-hydroxy butanal, respectively. In the case of oxidation of the secondary hydroxyl groups in 2-methyl pentane-2,4-diol and 3-methyl pentane-2,4-diol, the products of oxidation were 4-hydroxy-4-methyl pentan-2-one and 4-hydroxy-3-methyl pentan-2-one, respectively.     

Chemiluminescence determination of sodium 2-mercaptoethane sulfonate by flow injection analysis using cerium(IV) sensitized by quinine

A flow injection method with chemiluminescence (CL) detection is proposed for the determination of sodium 2-mercaptoethane sulfonate (MESNA), a drug often used to reduce the urotoxic effects of antineoplastic alkylating agents. The procedure is based on the reaction of the thiol with Ce(IV) in a sulfuric acid medium and measurement of the CL intensity produced by quinine used as a sensitizer. The optimum conditions for CL emission were investigated. Using the CL peak height as the analytical parameter, MESNA was determined over the concentration range 0.29–2.21 ng (1.97–9.85 μg·l⁻¹) with a detection limit of 0.21 ng (1.38 μg·l⁻¹) and a relative standard deviation (R.S.D.) of 4.1%. The method was applied satisfactorily to the determination of MESNA in pharmaceutical preparations with percentages of recovery between 94 and 105.     

Spectrofluorometric determination of ketorolac tromethamine via its oxidation with cerium(IV) in pharmaceutical preparations and biological fluids

A simple and sensitive fluorometric method for determination of ketorolac tromethamine was studied. The method depends on oxidation of the drug with cerium(IV) and subsequent monitoring of the fluorescence of the induced cerium(III) at lambda(em) 365 nm after excitation at 255 nm. Different variables affecting the reaction conditions, such as the concentrations of cerium(IV), sulfuric acid concentration, reaction time, and temperature, were carefully studied and optimized. Under the optimum conditions, a linear relationship was found between the relative fluorescence intensity and the concentration of the investigated drug in the range of 0.1-0.8 microg/mL. No interferences could be observed from the excipients commonly present in dosage forms. The proposed method was successfully applied to the analysis of the investigated drug in its pure form, pharmaceutical preparations, and biological fluids with good accuracy and precision. The recoveries for pharmaceutical formulations ranged from 99.8-101.0 +/- 0.6% for tablets, 98.5-101.0 +/- 1.0% for ampoules, and 99.0-100.5 +/- 0.7% for eye drops. The results obtained by the proposed method were satisfactory compared with those obtained by the official method. The recoveries for biological fluids were 99.1-100.4 +/- 0.7 and 99.0-100.0 +/- 0.5% for plasma and urine, respectively.     

Simultaneous chemiluminescence determination of thebaine and noscapine using support vector machine regression

In this work, a batch chemiluminescence (CL) method has been proposed for the simultaneous determination of two structurally similar alkaloids, noscapine and thebaine. The method is based on the kinetic distinction of the CL reactions of noscapine and thebaine with Ru(bipy)₃²⁺ and Ce(IV) system in a sulfuric acid medium. The least squared support vector machine (LS-SVM) regression was applied for relating the concentrations of both compounds to their CL profiles. The parameters of the model consisting of σ² and γ were optimized by constructing LS-SVM models with all possible combinations of these two parameters to select the model with the minimum root mean squared error of cross validation (RMSECV) as the best. The parameters of this model were then selected as optimized values. Under the optimized experimental conditions for both compounds, the detection limits obtained using the LS-SVM regression were 0.08 and 0.1 μmol L^?1 for noscapine and thebaine, respectively. The proposed method was utilized for the simultaneous determination of the compounds in pharmaceutical formulations and plasma samples with satisfactory results.     

Spectrofluorimetric Determination of the Hypertensive Drug Captopril Based on Its Oxidation with Cerium(IV)

A highly sensitive and specific spectrofluorimetric method for the analysis of captopril (CAP) in the pure form and in the tablet dosage forms has been described. The method was based on the oxidation of captopril by cerium(IV) in the presence of sulphuric acid and subsequent monitoring the fluorescence of the induced Ce(III) ion produced at λ_ex = 256 nm and λ_em = 354 nm. All variables affecting the reaction conditions such as cerium(IV) concentration, type and concentration of acid medium, reaction time, diluting solvents, temperature and heating time were carefully studied and optimized. Under the experimental conditions used, an excellent linear relationship was obtained between fluorescence intensity and the concentration of CAP. A linear range of determination was verified for captopril concentrations between 0.1–1.3 μg mL^?1 and the correlation coefficient of determination was 0.9997. Quantitation and detection limits were calculated. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 1.14%. No interference could be observed from the excipients and additives are commonly presented in dosage forms. The proposed method was applied successfully for the assay of the studied drug in pure form and in pharmaceutical dosage forms. Recovery experiments revealed recovery of 99.82–100.21%. The results of the analysis show a good agreement with those obtained by official method stated in the United State Pharmacopoeia.     

Polymerization of acrylamide with ceric ion–malic acid redox pair

The polymerization of acrylamide (M) in aqueous sulfuric acid medium initiated with ceric ammonium sulfate–malic acid redox pair was investigated at 35 ± 0.2°C under nitrogen atmosphere. The initiation was caused by the free radical generated by the decomposition of the complex formed between ceric ion and malic acid (MA). The rate of monomer disappearance was proportional to the first power of malic acid, ceric ion, and monomer concentrations at lower ceric ion concentrations. However, at higher ceric ion concentrations the rate was independent of [Ce(IV)]. The rate of ceric ion disappearance was proportional to [MA] and [Ce(IV)] but independent of [M] at lower ceric ion concentrations. The activation energy was found to be 57.74 kJ/mol. Sulfuric acid retarded the reaction. Molecular weights increased with increasing [M] and decreasing [Ce(IV)].     

Spectrophotometric determination of H(2)-receptor antagonists via their oxidation with cerium(IV)

A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of H(2)-receptor antagonists: cimetidine, famotidine, nizatidine and ranitidine hydrochloride. The method was based on the oxidation of these drugs with cerium(IV) in presence of perchloric acid and subsequent measurement of the excess Ce(IV) by its reaction with p-dimethylaminobenzaldehyde to give a red colored product (lambda(max) at 464nm). The decrease in the absorption intensity of the colored product (DeltaA), due to the presence of the drug was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990-0.9994) were found between DeltaA values and the concentrations of the drugs in a concentration range of 1-20microgml(-1). The assay limits of detection and quantitation were 0.18-0.60 and 0.54-1.53microgml(-1), respectively. The method was validated, in terms of accuracy, precision, ruggedness and robustness; the results were satisfactory. The proposed method was successfully applied to the determination of the investigated drugs in pure and pharmaceutical dosage forms (recovery was 98.3-102.6+/-0.57-1.90%) without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.     

Factorial design and response surface optimization of spectrophotometric sequential injection analysis of olanzapine formulations

A new spectrophotometric sequential injection analysis (SIA) method for the assay of olanzapine in pharmaceutical formulations was optimized by the factorial design and the response surface approaches. The method was based on the oxidation of olanzapine by an excess amount of permanganate in sulfuric acid media. The reduction of permanganate was spectrophotometrically detected at 570 nm. The 2³ full factorial design was adopted for the optimization of permanganate concentration, sulfuric acid concentration and flow rate. The method was validated based on the IUPAC guidelines. Real pharmaceutical samples were subjected to the proposed SIA method and the results were in satisfactory agreement with those obtained by a previous spectrophotometric method. The full-automation of SIA empowered the proposed method with high repeatability (RSD 1.74%, n = 7) and intermediate-precision (RSD 2.53%, n = 5). Additionally, both automation and miniaturization offered high sampling frequency (26 samples/h). Furthermore, the employment of chemometric optimization enhanced sensitivity of the method with limits of detection and quantification of 1.07 and 3.57 mg/L, respectively. Comparing with previous olanzapine assay methods, which employing conventional analytical techniques, the new SIA method is inexpensive in terms of instrumentation, consumption of reagents and samples as well as effort and manpower. The SIA method is also safer for handling solutions and for the environment.     

Interaction of some steroids with inorganic species in the presence of concentrated sulfuric acid: Kinetic-fluorometric study

The influence of 30 ionic species added previously to the addition of concentrated sulfuric acid on three steroids was studied. It has been proven that in the presence of some ionic species (Mg(II), Cr(III), Ce(IV), …) formation of fluorescent products occurs to a higher extent, permitting the establishment of methods for their determination. This process was investigated and the experimental variables and interference in each determination were reported.     

Oxidative polymerization of pyrrole in polymer matrix

The oxidative matrix polymerization of pyrrole (Py) by Ce(IV) in the presence of Polyacrylic acid (PAA) has been studied to obtain water-soluble and insoluble products. The role of the PAA, Pyrrole, and Ce(IV) concentration, order of component addition, the structure of polymer matrix (PAA, Hydroxy Ethyl Cellulose (HES), Poly-N-vinylpyrrolidone (PVP)], and model unit of PAA (propionic acid), on the polymerization system were investigated. Interaction of PAA with insoluble polypyrrole (PPy) and the interpolymer complex formation were investigated along with the aggregation of PPy onto the matrix polymer followed by spectral shifts. FTIR results of insoluble products obtained from the PAA–Py–Ce(IV) system and solubility of the system is explained in light of the mechanism of the polymerization of pyrrole on the polymer matrix. © 1995 John Wiley & Sons, Inc.