N-bromosuccinimide In Acid Medium Research Articles

AUTOMATED FLOW INJECTION SPECTROPHOTOMETRIC DETERMINATION OF THE PROTON PUMP INHIBITOR OMEPRAZOLE IN PHARMACEUTICAL FORMULATIONS

A simple and fast flow-injection method for the determination of omeprazole in pharmaceutical preparations is proposed. Detection of the drug is based on the measurement of the absorption signals for the product resulting from the oxidation of omeprazole with N-bromosuccinimide in acidic medium. A flow rate of 0.5 ml/min was pumped and active material was detected at 370 nm. Limit of detection (LOD) and limit of quantitation (LOQ) were calculated to be 2.0 and 6.5 μg/ml, respectively. No interference was observed from common pharmaceutical additives. The method was successfully applied to the assay of omeprazole in capsule preparations and in spiked human plasma. The results were statistically compared with those of the official high-performance liquid chromatography (HPLC) method of the USP by applying Student’s t-test and F-test.

Utilization of N-bromosuccinimide for the sensitive spectrophotometric determination of pipazethate HCl as antitussive drug in pure and dosage forms

Three simple, sensitive, precise, reproducible and validated spectrophotometric methods have been developed for the quantification of pipazethate HCl as antitussive drug in pure and dosage forms. The methods are based on utilization of N-bromosuccinimide as an oxidant and three dyes, amaranth, methylene blue, and indigo carmine, as auxiliary reagents. The proposed methods are based on oxidation reaction of pipazethate HCl with a known excess of N-bromosuccinimide in acid medium, followed by determination of unreacted N-bromosuccinimide by the reaction with a fixed amount of dyes, amaranth, methylene blue, and indigo carmine followed by the measurement of the absorbance at 520, 663 and 610nm, respectively. The optimization of the reaction conditions was investigated. Under the optimum conditions, linear relationships with good correlation coefficients (0.9998-0.9999) were found over the concentration ranges of 0.3-9.0, 0.5-12 and 0.5-10μgmL-1 with a limit of detection (LOD) of 0.1, 0.15 and 0.15μgmL-1 using amaranth, methylene blue, and indigo carmine methods, respectively. Intra-day and inter-day accuracy and precision of the methods have been evaluated. No interference was observed from the common tablet excipients. The developed methods were validated in accordance with ICH guidelines and successfully applied to the analysis of pipazethate HCl in dosage forms with good accuracy and precision. The reliability of the methods was further ascertained by performing recovery studies via the standard addition method. Statistical comparison of the results obtained by applying the proposed methods with those of the reported method by applying Student's t-test and variance ratio F-test at the 95% confidence level revealed good agreement and indicates no significant difference in accuracy and precision.

Spectrophotometric Determination of Salbutamol Sulphate and Mefenamic Acid Using Azur-A Dye in Presence of Oxidizing Agent N-bromosuccinimide

A simple, accurate and sensitive indirect spectrophotometric method has been developed for the determination of salbutamol sulphate and mefenamic acid in pure forms and in pharmaceutical preparations (capsule, syrup, tablet). This method based on the bromination of the drug with N-bromosuccinimide in acidic medium and the unreacted oxidizing agent react with constant amount of Azur-A dye solution due to bleach their colour and measured the absorbance of the residual colour dye at 606.5 nm.The molar absorptivity for salbutamol sulphate and mefenamic acid are 2.3 × 104 L.mol-1.cm-1 and 8.1× 103 L.mol-1.cm-1 respectively. Beer's Law was obeyed over the concentration range of 1.6 -12.8 µg/ml for salbutamol sulphate and1.6 -13.6 µg/ml for mefenamic acid. The limit of detection (LOD) were 0.0367µg/ml and limit of quantitation (LOQ) were 0.1226 µg/ml for both drugs. In addition, the recovery levels of the drugs were in the range 100.56% and 100.74%. The method was created to be simple, cost-effective and rapid because it does not involve any solvent extraction. The developed method was successfully applied for the determination of the studied drugs.

Indirect Spectrophotometric Determination of Diclofenac and Isoxsuprine Drugs Using N-bromosuccinimide and Malachite Green Dye

Simple, accurate and sensitive indirect spectrophotometric method for assay of diclofenac (Di) and Isoxsuprine (IS) in pure and pharmaceutical formulation has been developed. The method is based on oxidation of (Di) and (IS) by N-bromosuccinimide in acidic medium. The excess of oxidant is determine by reaction with malachite green dye and the absorbance is measured at 615nm. Under the optimized experimental conditions, Beer's law is obeyed in concentration range 0.5-18 , 1-18 µg/ml with molar absorptivity 5.1×104 and 4.6×104 L.mol-1.cm-1 for (Di) and (IS) respectively. The limits of detection (LOD) 0.0314, 0.038 and quantification are 0.0104 , 0.126 µg/ml. with the accuracy (average recovery) 100.80%, 101.20% for above drugs respectively and the precision (RSD) less than 1.5% for both drugs. The proposed method is applied successfully for assay of pharmaceutical formulations.

Spectrophotometric and potentiometric determination of some organophosphorus pesticides in bulk powder and in their dosage forms

Two simple, sensitive and precise methods were developed and validated for determination of diazinon, chlorpyrifos and temefos pesticides in bulk powder and dosage forms. The spectrophotometric method involves the oxidation of these pesticides with potassium iodate in acidic medium with the liberation of iodine and subsequent extraction with cyclohexane followed by measuring the absorbance at λ = 520 nm. Beer`s law is obeyed in the concentration range of 0.05–1.00 mg ml for diazinon and chlorpyrifos and 0.05–0.6 mg ml for temefos. The apparent molar absorbitivities of the resulting coloured products are found to be 0.539×103, 0.368×103 and 0.474×103 L mol−1 cm−1 for diazinon chlorpyrifos and 0.05–0.6 mg ml−1 for 0.368×103 and 0.474×103 L mol−1 cm−1 or diazinon, chlorpyrifos and temeos, respectively, whereas Sandell sensitivities are 0.5647, 0.9527 and 0.9841 µg cm −2, respectively. The potentiometric method involves the direct titration of the studied pesticides with N-bromosuccinimide in acidic medium and the end point is determined potentiometricallyusing platinum indicator electrode. The ratio of drug: NBS was 1:3 for diazinon andchlorpyrifos and 1:6 for temefos. The proposed methods were successfully applied to the analysis of the studied pesticides in bulk powder and in dosage forms without interference from other additives.

Automated Flow Injection Spectrophotometric Determination of the Proton Pump Inhibitor Omeprazole in Pharmaceutical Formulations

A simple and fast flow-injection method for the determination of omeprazole in pharmaceutical preparations is proposed. Detection of the drug is based on the measurement of the absorption signals for the product resulting from the oxidation of omeprazole with N-bromosuccinimide in acidic medium. A flow rate of 0.5 ml/min was pumped and active material was detected at 370 nm. Limit of detection (LOD) and limit of quantitation (LOQ) were calculated to be 2.0 and 6.5 μg/ml, respectively. No interference was observed from common pharmaceutical additives. The method was successfully applied to the assay of omeprazole in capsule preparations and in spiked human plasma. The results were statistically compared with those of the official high-performance liquid chromatography (HPLC) method of the USP by applying Student’s t-test and F-test.

Studies on the oxidation of levofloxacin by N-bromosuccinimide in acidic medium and their mechanistic pathway

Kinetics and mechanism of oxidation of levofloxacin(LF) by N-bromosuccinimide (NBS) have been studied in acid medium with pH and ionic strength at 25°C. It is a first order reaction with respect to both LF and NBS, but inverse first order in succinimide (reduction product of NBS). The stoichiometry of the reaction is 1:2 in this investigation. The effects of added products, halide ion and ionic strength have also been investigated. Polymerization was not observed with acrylonitrile. The main oxidation products as, (3S)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-5,7-dioxo-2,3,6,7-tetrahydro-5H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid and succinimide were identified by Fourier transform infrared spectroscopy (FTIR), Liquid chromatography–mass spectrometry (LC–MS), Nuclear magnetic resonance (NMR) and Thin-layer chromatography (TLC) data. The rate of reaction was examined with reference to variation of ionic strength, solvent polarity, free radicals, halides ions, mercuric acetate for fix up the Br− in reaction mixture and also addition of the product succinamide (RNH).·On the basis of the experimental results, the mechanism of the reaction has been proposed and supported by kinetic orders, spectrophotometric evidence and negative entropy of activation parameters.

Kinetic Treatment of the Reaction of Fructose and N-Bromosuccinimide in Cationic/Anionic/Nonionic Micelles

The kinetics of oxidation of fructose by N-bromosuccinimide in acidic medium in the absence and presence of cationic, anionic, and nonionic surfactants has been measured iodometrically under pseudo-first-order condition. The oxidation kinetics of fructose by N-bromosuccinimide shows a first-order dependence on N-bromosuccinimide, fractional order dependence on fructose, and negative fractional order dependence on sulfuric acid. The kinetics is treated using Berezin’s micellar model that was previously used for the catalysis and inhibition of the reaction. The determined stoichiometric ratio was 1 : 1 (fructose : N-bromosuccinimide). The variation of Hg(OAC)2and succinimide (reaction product) has insignificant effect on reaction rate. Effects of surfactants, added acrylonitrile, added salts, and solvent composition variation have been studied. Activation parameters for the reaction have been evaluated from Arrhenius plot by studying the reaction at different temperatures. The rate law has been derived on the basis of obtained data. A plausible mechanism has been proposed from the results of kinetic studies, reaction stoichiometry, and product analysis.

Kinetics of Oxidation of Diazepam by N Bromosuccinimide in Acid Medium: A Mechanistic Study

The oxidation of diazepam (DZ) by N-Bromosuccinimide (NBS) in aqueous acid medium follows a first -order kinetics in [NBS] and a fractional -order each on [HCl]and [DZ]. The reaction stoichiometry involves one mol NBS consumed by one mol DZ. The rate of the reaction increases with the decrease in dielectric constant of the medium. Added products and the variation of ionic strength have no significant effect o n the rate of the reaction. The oxidation products were identified by spectral analysis. A mechanism OriginalResearch Article

Spectrophotometric determination of some analgesic drugs in pharmaceutical formulations using N-bromosuccinimide as an oxidant

New sensitive and rapid spectrophotometric methods for the determination of four analgesic drugs namely, nalbuphine (NALB), naltrexone (NALT), morphine (MORF) and tramadol (TRAM) in pharmaceutical formulations were developed and optimized. The proposed methods involve the addition of a measured excess of N-bromosuccinimide in acid medium followed by determination of unreacted NBS by reacting with either a fixed amount of methyl orange and measuring the absorbance at 508nm (Method A), or orange G and measuring the absorbance at 478nm (Method B). In both methods, the amount of NBS reacted corresponds to the amount of drugs. Under the optimum conditions, Beer’s law limit, molar absorptivity and Sandell’s sensitivity were calculated. The limits of detection and quantification were also reported for both methods. Statistical evaluation of the methods was examined by determining intra-day and inter-day precisions. The methods were successfully applied to the assay of drugs in their pharmaceutical formulations. No interference was observed from common additives and the validity of the methods was tested.

Utilization ofN-Bromosuccinimide as a Brominating Agent for the Determination of Sumatriptan Succinate in Bulk Drug and Tablets

One titrimetric and two spectrophotometric methods which are simple, sensitive, and economic are described for the determination of sumatriptan succinate (STS) in bulk drug and in tablet dosage form using N-bromosuccinimide (NBS) as a brominating agent. In titrimetry, aqueous solution of STS is treated with a measured excess of NBS in acetic acid medium, and after the bromination of STS is judged to be complete, the unreacted NBS is determined iodometrically (method A). Spectrophotometric methods entail addition of a known excess of NBS in acid medium followed by the determination of residual NBS by its reaction with excess iodide, and the liberated iodine (I3 −) is either measured at 370 nm (method B) or liberated iodine is reacted with starch followed by the measurement of the blue colored starch-iodine complex at 570 nm (method C). Titrimetric method is applicable over range 1.0–10.0 mg STS (method A), and the reaction stoichiometry is found to be 1 : 3 (STS : NBS). The spectrophotometric methods obey Beer's law for concentration range 0.6–15.0 μg mL−1 (method B) and 0.2–4.0 μg mL−1 (method C). The calculated apparent molar absorptivity values were found to be 2.10 × 104 and 7.44 × 104 L mol−1 cm−1, for method B and method C, respectively.

Ciprofloxacin and Norfloxacin Spectrophotometric Determination in a Fully Automated Multi-Pumping Flow System

A flow-based methodology for the spectrophotometric determination of ciprofloxacin and norfloxacin, based on the oxidation with N-bromosuccinimide in acidic medium, was developed. The proposed procedure was implemented in a multi-pumping flow system, which provided excellent mixing conditions due to the pulsed flow produced by solenoid micro-pumps actuation, resulting on a sensitive, simple, fast, and versatile analytical method. Linear calibration plots were obtained for ciprofloxacin and norfloxacin concentrations ranging from 5 to 70 mg L−1 with an R.S.D < 2.2% (n = 10). Detection limits (3σ) were 0.27 mg L−1 and 0.99 mg L−1 for norfloxacin and ciprofloxacin, respectively.

Mechanistic investigation of oxidation of metronidazole and tinidazole with N-bromosuccinimide in acid medium: A kinetic approach

Metronidazole (MTZ) and tinidazole (TNZ) belong to nitroimidazole group of drugs used to treat infections such as ameobiasis, giardiasis and trichomoniasis. The kinetics of oxidation of MTZ and TNZ with N-bromosuccinimide (NBS) in perchloric acid medium has been investigated at 308 K. A 1:1 stoichiometry has been observed in both MTZ and TNZ cases. The oxidation reactions of both MTZ and TNZ follow the same rate law, -d[NBS]/dt = [NBS][Sub][H+]. However, in case of MTZ, at higher concentrations of H+ (0.006–0.01 mol dm−3), the rate law obtained is -d[NBS]/dt = [NBS][MTZ][H+]−1. Accelerating effect of [Cl-] and retardation of the added succinimide on the reaction rate have been observed in the case of MTZ. The reactions were examined with reference to changes in concentration of added neutral salt, ionic strength and dielectric permittivity of the medium. The overall activation parameters have been evaluated from the Arrhenius plot. The reactive oxidizing species of NBS have been determined. The main oxidation products were identified by IR and 1H NMR spectral analyses. The observed results have been explained by plausible mechanisms and the relative rate laws have been deduced.

Rapid titrimetric and spectrophotometric methods for salbutamol sulphate in pharmaceuticals using N-bromosuccinimide

One titrimetric and two spectrophotometric methods which are simple, sensitive and rapid are described for the assay of salbutamol sulphate (SBS) in bulk drug and in tablet dosage forms using N-bromosuccinimide (NBS) and two dyes, rhodamine-B and methylene blue, as reagents. In titrimetry, aqueous solution of salbutamol sulphate is treated with a measured excess of NBS in acetic acid medium and after the oxidation of SBS is complete, the unreacted oxidant is determined iodometrically. Spectrophotometric methods entail addition of a known excess of NBS in acid medium followed by the determination of residual oxidant by reacting with a fixed amount of either rhodamine B and measuring the absorbance at 555 nm (method A) or methylene blue and measuring the absorbance at 665 nm (method B). In all methods, the amount of NBS reacting corresponds to the amount of SBS content. Titrimetric method is applicable over 1.74 x 10(-4) - 8.68 x 10(-4) mol L(-1) range and the reaction stoichiometry is found to be 1:6 (SBS:NBS). In spectrophotometric methods, the absorbance is found to increase linearly with the concentration of SBS, which is corroborated by the correlation of coefficients of 0.9993 and 0.9988 for method A and method B, respectively. The systems obey Beer's law for 0.25-1.75 microg mL(-1) (method A) and 0.5-5.0 microg mL(-1) (method B). The calculated apparent molar absorptivity values were found to be 2.10 x 10(5) and 6.16 x 10(4) L mol(-1) cm(-1), for method A and method B, respectively. The limits of detection and quantification are also reported for both spectrophotometric methods. Intra-day and inter-day precision and accuracy for the developed methods were evaluated. The methods were successfully applied to the assay of SBS in tablet and capsule formulations and the results were statistically compared with those of a reference method. No interference was observed from common tablet adjuvants. The accuracy and reliability of the methods were further ascertained by recovery experiments via the standard-addition technique.

Spectrophotometric Determination of Olanzapine by Its Oxidation with N-Bromosuccinimide and Cerium(IV)sulfate

Three simple spectrophotometric methods have been described for the assay of olanzapine in its pure and pharmaceutical formulations. The direct method (A) is based on the drug oxidation with excess of N-bromosuccinimide in acidic medium and the two indirect methods (B and C) are based on the oxidation of the drug with excess of N-bromosuccinimide and cerium(IV)sulfate, followed by the reaction of the unconsumed oxidants with celestine blue. The calibration graphs were linear over the range 10 - 120 microg mL(-1) (method A), 0.5 - 6.0 microg mL(-1) (method B) and 0.6 - 3.0 microg mL(-1) (method C). After validation, the proposed methods were successfully applied to assay of olanzapine in its commercial tablets with mean percentage recoveries of 101.23 +/- 0.10, 96 +/- 0.10 and 94 +/- 0.04%. The mechanism of olanzapine oxidation with N-bromosuccinimide was also proposed.

Kinetic study of iridium(III) catalyzed oxidation of D-mannitol and erythritol by N-bromosuccinimide in acidic medium

Kinetic investigations on iridium trichloride catalyzed oxidation of D-mannitol and erythritol by acidic solution of N-bromosuccinimide (NBS) in the presence of mercuric acetate as a scavenger for Br - have been carried out in the temperature range 30-45 °C. The reactions follow identical kinetics. The rate shows a first-order dependence on [NBS] in lower concentration range which tends to zero-order at its higher concentrations. A first-order dependence on [Ir III ] is also observed. Negligible effect of [substrate], [Hg(OAc) 2 ] and ionic strength have been observed. Addition of [H + ], [Cl-] and succinimide shows a negative effect. Activation parameters have been computed and a suitable mechanism conforming to above results has been proposed.

Spectrophotometric and potentiometric determination of piroxicam and tenoxicam in pharmaceutical preparations.

Two simple and accurate methods are described for the determination of piroxicam and tenoxicam in their pharmaceutical preparations. The spectrophotometric method involves the oxidation of these drugs with potassium iodate in acid medium with the liberation of iodine and subsequent extraction with cyclohexane followed by measuring the absorbance at lambda=522 nm. Beer's law is obeyed in the concentration range of 0.05-1.1 and 0.05-0.6 mg x ml(-1) for piroxicam and tenoxicam, respectively. The apparent molar absorptivities of the resulting coloured products are found to be 2.7 x 10(3) and 2.5 x 10(3) l mol(-1) x cm(-1), whereas Sandell sensitivities are 0.012 and 0.013 g x cm(-2) for piroxicam and tenoxicam, respectively. The potentiometric method involves the direct titration of both drugs with N-bromosuccinimide in acid medium and the end point is determined potentiometrically using platinum indicator electrode. Piroxicam and tenoxicam can be determined quantitatively in the concentration range of 0.33-3.37 and 0.33-4.08 mg x ml(-1) for tenoxicam and piroxicam, respectively. The standard deviation and relative standard deviation values are found to be ranged from 0.05-0.07 and 0.37-0.98% and 0.025-0.078 and 0.25-1.2% for tenoxicam and piroxicam, respectively. The two methods are accurate within +/-1.0%. Optimum conditions affecting both methods are studied. The proposed methods are applied for the determination of the drugs in pure form and in commercial pharmaceutical preparations.