Colored Charge Transfer Research Articles

DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION AND SPECTROSCOPIC CHARACTERIZATION OF VILDAGLIPTIN USING II -ACCEPTORS IN PHARMACEUTICAL PREPARATIONS

ABSTRACT Three simple, quick and sensitive methods are described for the spectrophotometric determination of vildagliptin (VLD) in pharmaceutical preparations. The methods are based on formation of colored charge transfer (CT) complexes between VLD as n-electron donor and chloranilic acid (CA), tetrachloro-1,4-benzoquinone ( p-chloranil), 7,7,8,8-tetracyanoquinodimethane (TCNQ) as π-acceptors. The colored products were quantitated spectrophotometrically at 520, 535 and 842 nm for CA, p-chloranil and TCNQ methods, respectively. Optimization of different experimental conditions were investigated. Beer’s law was obeyed in the concentration range of 20-250 µg mL -1 , 25-400 µg mL and 20-500 µg mL -1 for CA, p-chloranil and TCNQ methods, respectively. The formation of the CT-complexes and the sites of interactions were confirmed by elemental analysis using IR, 1 H NMR spectroscopy. Validity of the methods in terms of specificity, linearity, accuracy, precision, robustness, limit of detection and limit of quantitation were evaluated. Good recoveries were obtained for all of the methods indicating that no interference was observed from concomitants usually present in dosage forms. The methods were applied successfully to the determination of VLD in pharmaceutical preparations.

Spectroscopic Studies on Charge Transfer Complexes of Chloranil with Novel 6-(Trifluoromethyl)furo[2, 3-b] pyridine-2-carbohydrazide Derivatives

A sensitive spectrophotometric method was employed to study the charge transfer complex of chloranil with 6-(trifluoromethyl)furo(2, 3-b)pyridine-2-carbohydrazide derivatives (TFC). The method is based on the reaction of these drugs as n-electron donors with the pi-acceptor 2,3,5,6-tetrachloro-1,4-benzoquinone. The obtained coloured charge transfer complex was measured at 412 nm by UV-Vis spectrophotometer. The obtained complexes were confirmed by 1 H NMR and IR spectral analysis. The proposed procedure could be applied successfully to the determination of the association constants and standard free energy changes using Benesi-Hildebrand plots.

High throughput microwell spectrophotometric assay for olmesartan medoxomil in tablets based on its charge-transfer reaction with DDQ

The study describes the development and validation of a new microwell-based spectrophotometric assay for determination of olmesartan medoxomil (OLM) in tablets. The formation of a colored charge-transfer (CT) complex between OLM as an n-electron donor and 2,3-dichloro- -5,6-dicyano-1,4-benzoquinone (DDQ) as a p-electron acceptor was investigated, and employed as the basis for the development of the new assay. The proposed assay was conducted in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm with a microplate reader. Optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, a linear relationship with a good correlation coefficient was found between the absorbance and the concentration of OLM in the range of 2-200 μg per well. The limits of detection and quantitation were 0.53 and 1.61 μg per well, respectively. No interference was observed from the excipients present in OLM tablets or from hydrochlorothiazide and amlodipine besylate that were co-formulated with OLM in some of its formulations. The assay was successfully applied to the analysis of OLM in tablets with good accuracy and precision. The assay described herein has a great practical value in the routine analysis of OLM in quality control laboratories, since it has a high throughput property and consumes low volumes of organic solvent. It thus offers a reduction in the exposure of analysts to the toxic effects of organic solvents, as well as a reduction in the cost of analysis.

Spectrophotometric determination of Sulphamethoxazole Via Charge Transfer Complex Formation Reaction

A simple and sensitive spectrophotometric method for the determination of sulphamethoxazole in pure as well as in dosage form is described. The method is based on the reaction of sulphamethoxazole as electron donor with o-chloranil as electron acceptor to form violet colored charge transfer complex having maximum absorption band at 539 nm. Under the optimized reaction conditions, Beer’s law was obeyed in the range of 2-60 μg ml-1 with molar absorptivity 3.675×103 L mol−1cm−1. The limits of detection (LOD) and limit of quantitation (LOQ) were 0.371 and 1.236 μg ml-1 respectively. The accuracy and precision of the method were satisfactory; the average recovery % was 100.95 % and values of relative standard deviations ≤1.06 %. The stoichiometry of the reaction was studied, and the reaction mechanism was postulated. The proposed method was successfully applied to the determination of sulphamethoxazole in its pharmaceutical tablets and syrup with good accuracy and precisions. Keywords: Charge transfer; Spectrophotometry; o-chloranil; sulphamethoxazole

Novel Microwell-Based Spectrophotometric Assay for the Determination of Rosuvastatin Calcium in its Pharmaceutical Formulations

A novel 96-microwell-based spectrophotometric assay has been developed and validated for the determination of rosuvastatin calcium (ROS-Ca) in tablets. The formation of a colored charge-transfer (CT) complex between rosuvastatin calcium (ROS-Ca) as n-electron donor and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a π-electron acceptor was investigated, for the first time. The spectral characteristics of the CT complex have been described, and the reaction mechanism has been proved by computational molecular modeling. The reaction was employed in the development of a novel microwell-based spectrophotometric assay for the determination of ROS-Ca in its pharmaceutical formulations. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient (0.9987) was found between the absorbance and the concentration of ROS-Ca in the range of 10-100 μg/well. The limits of detection and quantitation were 2.6 and 7.85 μg/well, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from the drugs that are co-formulated with ROS-Ca in its combined formulations. The assay was successfully applied to the analysis of ROS-Ca in its pharmaceutical dosage forms with good accuracy and precision. The assay described herein has great practical value in the routine analysis of ROS-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposure of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50- fold. Although the proposed assay was validated for ROS-Ca, however, the same methodology could be used for any electron- donating analyte for which a CT reaction can be performed.

Spectrophotometric Determination of Quinolones by Charge Transfer Complexation with Chloranilic Acid: Synthesis and Characterization

A simple and sensitive spectrophotometric method has been described for the assay of quinolones in bulk drug and in pharmaceutical formulations. The developed method is based on the formation of colored charge transfer complexes of quinolones with chloranilic acid in acetonitrile solvent. The formed complexes absorbed at 417, 436, 419 and 436 nm for sparfloxacin, enoxacin, norfloxacin and levofloxacin respectively. Beer's law is obeyed in the concentration range of 0.5-7, 1-10, 1-10 and 1-5 µg mL -1 with LLOD values 0.036, 0.0041, 0.0344 and 0.0063 ng mL-1 respectively. The data are discussed in terms of molar absorptivity, association constant and Gibb's free energy. Spectral characteristics including oscillator's strength, dipole moment, ionization potential, energy of complexes and resonance energy have been determined. Benesi-Hildebrand plots for each complex have been constructed. Structural characteristics of synthesized charge transfer complexes were determined by IR spectroscopy. The applicability of the method was demonstrated by determination of studied drugs in commercial tablets with satisfactory results. No interference from excipients was observed in the formulation.

Synthesis and Spectrophotometric Determination Ibuprofen Charge Transfer Complexes with P-Chloranil, 7,7,8,8-Tetracyanoquinodimethane, Bromothymol Blue, Methyl Orange and Picric Acid

Three simple, sensitive and inexpensive spectrophotometric methods have been described for the assay of ibuprofen in bulk drugs and pharmaceutical formulations. The developed methods are based on the formation of colored charge transfer complexes of ibuprofen with p-chloranil, 7,7,8,8-tetracyanoquinodimethane, bromothymol blue, methyl orange and picric acid in acetonitrile as solvent. These newly formed complexes were found to absorb at 438, 394, 403, 418, 374 nm respectively. Optimizations of various experimental conditions are described. Beer’s law obeyed in the concentration range6-54, 2-24, 4-28, 3-21 and 4-28 μgmL-1 with correlation coefficient >0.998 in each case and lower limit of detection values were 76, 90, 234, 63 and 189 ng mL-1, respectively. The association constants and standard free energy changes were studied using Benesi-Hildebrand plots. Oscillator’s strength, ionization potential and energy of complexes in the ground state for all the complexes have been calculated. For further confirmation, solid charge transfer complexes were synthesized and characterized by IR and 1H-NMR spectroscopy. The applicability of the method was demonstrated by the determination of studied drugs in commercial tablets with satisfactory results. No interference from excipients was observed in the formulations.

Spectrophotometric Determination of Tiapride in Pharmaceutical Formulations

Simple, accurate and precise spectrophotometric method is presented for the determination of tiapride in its pharmaceutical formulations. The method is based on the reaction of the aliphatic amino group on tiapride as n-electron donor with p-chloranilic acid as a π-acceptor in acetone to yield a reddish coloured charge transfer complex product which absorbed at 520 nm. Beer's law is obeyed in the concentration range 10-100 µg/mL of tiapride with a correlation coefficient of 0.9999. The optimum experimental parameters for the reaction have been studied. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The suggested procedure could be used for the determination of tiapride in its pharmaceutical tablets.

Spectrophotometric Assay of some Nitrogen Containing Drugs in Pharmaceutical Formulations using p-Chloranilic Acid Reagent

A spectrophotometric method is developed for the determination of some drugs containing amino groups (sulfacetamide sodium, lidocaine and terbutaline sulfate) based on their reaction with p-chloranilic acid reagent in an organic medium forming colored charge transfer complexes. The complexes have maximum absorptions at 530 and 527 nm for sulfacetamide sodium and lidocaine respectively, but terbutaline sulfate gave two maximum absorptions at 529 and 319 nm. Beers law is obeyed over the concentration range of 10-60 µg.ml-1 for sulfacetamide sodium and lidocaine and 5-70 µg.ml-1 for terbutaline sulfate. The molar absorptivity values are 0.940×103, 0.913×103 L.mol-1.cm-1 for sulfacetamide sodium and lidocaine respectively while terbutaline sulfate gave 0.987×103 L.mol-1.cm-1 at 529 nm and 7.407×103 L.mol-1.cm-1 at 319 nm with accuracy range between 100.20% and 101.42% and RSD better than 3.15% for all drugs. The method is applied successfully for determination of these drugs in pharmaceutical formulations and compared favorably with British Pharmacopeia standard methods. F and t tests are less than the tabulated values at 95% confidence level.

Simple and rapid spectrophotometric assay of levocetirizine in pharmaceuticals through charge-transfer complexation using chloranilic acid and 2,3-dichloro-5,6-dicyanoquinone as π-acceptors

Simple, rapid, selective and fairly sensitive method is described for the determination of levocetirizine (LCTZ) in pure form and in its dosage forms. The method is based on the formation of intensely colored charge-transfer (CT) complexes between LCTZ as donor with two π acceptors, chloranilic acid (CAA) and 2,3-dichloro-5,6-dicyanoquinone (DDQ) in acetonitrile-dioxane medium. The colored products were measured at 520 nm (CAA) and 590 nm (DDQ). Optimization of experimentation conditions is described. Beer’s law is obeyed over the concentration ranges 3-120 and 2-80 µg mL-1 for CAA and DDQ reagents, respectively, with corresponding molar absorptivity values of 4.0×103 and 5.5×103 L mol cm-1. The limits of quantification (LOQ) are 2.99 and 1.69 µg mL-1 for above reagents, respectively. Other method validation parameters, such as accuracy, precision, robustness and ruggedness, and selectivity are also reported. The composition of CT complex was found to be 1:1. The proposed method was successfully applied to the determination of the active ingredient in commercial tablets; and the results were in good agreement with those obtained by the official method. KEY WORDS: Levocetirizine, Spectrophotometry, Charge-transfer complex, Pharmaceuticals Bull. Chem. Soc. Ethiop. 2012, 26(3), 319-328.DOI: http://dx.doi.org/10.4314/bcse.v26i3.1

Development of a novel 96-microwell assay with high throughput for determination of olmesartan medoxomil in its tablets

A novel 96-microwell-based spectrophotometric assay has been developed and validated for determination of olmesartan medoxomil (OLM) in tablets. The formation of a colored charge-transfer (CT) complex between OLM as a n-electron donor and 2, 5-dichloro-3, 6-dihydroxy-1, 4-benzoquinone (p-chloranilic acid, pCA) as a π-electron acceptor was investigated, for the first time, and employed as a basis in the development of the proposed assay. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 490 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient was found between the absorbance and the concentration of OLM in the range of 1-200 μg ml-1. The limits of detection and quantitation were 0.3 and 1 μg ml-1, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from hydrochlorothiazide and amlodipine that are co-formulated with OLM in some formulations. The assay was successfully applied to the analysis of OLM in tablets with good accuracy and precision. The assay described herein has great practical value in the routine analysis of OLM in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50-fold. Although the proposed assay was validated for OLM, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed.

Novel microwell-based spectrophotometric assay for determination of atorvastatin calcium in its pharmaceutical formulations

The formation of a colored charge-transfer (CT) complex between atorvastatin calcium (ATR-Ca) as a n-electron donor and 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a π-electron acceptor was investigated, for the first time. The spectral characteristics of the CT complex have been described, and the reaction mechanism has been proved by computational molecular modeling. The reaction was employed in the development of a novel microwell-based spectrophotometric assay for determination of ATR-Ca in its pharmaceutical formulations. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient (0.9995) was found between the absorbance and the concentration of ATR-Ca in the range of 10-150 μg/well. The limits of detection and quantitation were 5.3 and 15.8 μg/well, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from the drugs that are co-formulated with ATR-Ca in its combined formulations. The assay was successfully applied to the analysis of ATR-Ca in its pharmaceutical dosage forms with good accuracy and precision. The assay described herein has great practical value in the routine analysis of ATR-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50-fold. Although the proposed assay was validated for ATR-Ca, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed.

Colored supramolecular charge-transfer host system using 10,10′-dihydroxy-9,9′-biphenanthryl and 2,5-disubstituted-1,4-benzoquinone

A colored charge-transfer (CT) host complex is formed using racemic ( rac )-10,10′-dihydroxy-9,9′-biphenanthryl, which has a large and widely π-conjugated phenanthrene ring, as the electron donor and 2,5-disubstituted-1,4-benzoquinone as the electron acceptor. This CT host complex can include aromatic molecules as guests and its color and diffuse reflectance spectra (DRS) change according to the type of guest molecules included. Characteristically, it is possible to tune the color and DRS of the inclusion CT complex by changing the type of the component 2,5-disubstituted-1,4-benzoquinone.

Utility of certain σ- and π-acceptors for the spectrophotometric determination of ganciclovir in pharmaceutical formulations

Studies were carried out, for the first time, to investigate the charge–transfer reactions of ganciclovir as n-electron donor with the σ-acceptor iodine and various π-acceptors: 7,7,8,8-tetracyanoquinodimethane; tetracyanoethylene; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; p-chloranilic acid; 2,3,5,6-tetrabromo-1,4-benzoquinone; 2,3,5,6-tetrachloro-1,4-benzoquinone and 2,4,7-trinitro-9-fluorenone. The formation of the colored charge–transfer complexes was utilized in the development of simple, rapid and accurate spectrophotometric methods for the analysis of ganciclovir in pure form as well as in its pharmaceutical formulation (capsules). Different variables affecting the reactions were studied and optimized. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9993–0.9998) were found between the absorbance and the concentration of ganciclovir in the range of 2.0–240 μg mL −1. For more accurate analysis, Ringbom optimum concentration range was found to be between 5.0 and 225 μg mL −1. The limits of detection ranged from 0.36 to 2.45 μg mL −1 and the limits of quantification ranged from 1.20 to 8.17 μg mL −1. A Job's plot of the absorbance versus the molar ratio of ganciclovir to each of acceptors under consideration indicated (1:1) ratio. The proposed methods were applied successfully for simultaneous determination of ganciclovir in capsules with good accuracy and precision and without interferences from common additives. The recovery percentages ranged from 99.45 ± 0.73% to 100.35 ± 1.40%. The results were compared favourably with the reported method.

Exploiting π-acceptors for the determination of thyroid hormones (T3 and T4) using a single interface flow system

A fully automated methodology was developed for the determination of the thyroid hormones levothyroxine (T4) and liothyronine (T3). The proposed method exploits the formation of highly coloured charge–transfer (CT) complexes between these compounds, acting as electron donors, and π-acceptors such as chloranilic acid (CLA) and 2,3-dichloro-5,6-dicyano- p-benzoquinone (DDQ). For automation of the analytical procedure a simple, fast and versatile single interface flow system (SIFA) was implemented guaranteeing a simplified performance optimisation, low maintenance and a cost-effective operation. Moreover, the single reaction interface assured a convenient and straightforward approach for implementing Job's method of continuous variations used to establish the stoichiometry of the formed CT complexes. Linear calibration plots for levothyroxine and liothyronine concentrations ranging from 5.0 × 10 −5 to 2.5 × 10 −4 mol L −1 and 1.0 × 10 −5 to 1.0 × 10 −4 mol L −1, respectively, were obtained, with good precision (R.S.D. <4.6% and <3.9%) and with a determination frequency of 26 h −1 for both drugs. The results obtained for pharmaceutical formulations were statistically comparable to the declared hormone amount with relative deviations lower than 2.1%. The accuracy was confirmed by carrying out recovery studies, which furnished recovery values ranging from 96.3% to 103.7% for levothyroxine and 100.1% for liothyronine.

Origins of Selectivity in a Colorimetric Charge-Transfer Sensor for Diols

Bispyridyl hydrogen bonding receptor 1 forms colored charge transfer (CT) complexes with complementary phenols and naphthols. Despite its low association constants of approximately 10(1) M(-1), receptor 1 was highly selective forming CT complexes of varying color and intensity with different diol guests. The selectivity of 1 was correlated with the ability of its CT band to simultaneously yield information about the association constant and the electronic structure of the phenols and naphthols.

Determination of imipramine in presence of iminodibenzyl and in pharmaceutical dosage form

Two spectrophotometric methods for the determination of imipramine in presence of iminodibenzyl as an impurity are described. The first method is a ratio-spectra first derivative spectrophotometry, the signals were measured at 240.2 nm for imipramine. Calibration graph was found linear in the range 5–30 μg ml −1. The second method is based on the reaction of imipramine base, being an electron donor, with p-chloranilic acid, being π acceptor, to form a purple colored charge transfer complex. The absorbance was measured at 520.5 nm without interference with iminodibenzyl. Both methods are rapid, simple and do not require any preliminary separation or treatment of the samples. Furthermore, the two methods were applied to pharmaceutical dosage form.

A New Host for MnO&lt;sub&gt;4&lt;/sub&gt;&lt;sup&gt; 3-&lt;/sup&gt; : Synthesis and Characterisation of the NaCaV&lt;sub&gt;1­x&lt;/sub&gt;Mn&lt;sub&gt;x&lt;/sub&gt;O&lt;sub&gt;4&lt;/sub&gt; System

The incorporation of the intensely coloured charge transfer species MnO43- has been investigated for NaCaVO4. The series of compounds NaCaV1-xMnxO4 (where x = 0, 0.02, 0.04, 0.06, 0.08, 0.1) has been successfully prepared and results in the formation of blue/green coloured powders. A structural characterisation of the materials has been performed and the results are presented. The series is seen to adopt an orthorhombic structure in the space group Cmcm (No.63). On increasing manganese content an overall reduction of the cell volume was observed and the limit of substitution occurs at x 0.08.

Reactions of 2,3-dihydrospiro[1H-4- and 5-azabenzimidazole-2,1′-cyclohexane] with nucleophiles: A potential route to some substituted aromatic heterocycles

The readily available title compounds 2, 16 and 27 react with pseudohalogenes (cyanide, azide), carbon and heterocyclic N-nucleophiles in the presence of manganese dioxide to give the corresponding substituted azaisobenzimidazoles (= 2H-azabenzimidazoles) 4, 8, 23–26 and 29–33, 36 or dihydroazabenzimidazoles (= 2,3-dihydro-1H-azabenzimidazoles 7, 22, 34 and 35. In 8 one of the two imidazolyl-substituents can be replaced by nucleophiles yielding the compounds 9–15. Treatment of 6′-bromo-2,3-dihydro-4-azabenzimidazole 16 with morpholine or piperidine results in loss of the Br-atom presumably by an AEa-mechanism. Reduction of the substituted azaisobenzimidazoles with sodium hydrosulfite followed by fission of the cyclohexane ring leads to substituted o-diaminopyridines. They were cyclised in situ with various condens ing agents to give new heterocyclic systems. Equimolar mixtures of some azaisobenzimidazoles and dihydroazabenzimidazoles lead to the formation of coloured charge transfer complexes stable only in the solid state. Owing to poor electron-acceptor properties the complex dissociates in solution.

Caffeine interaction with synthetic flavylium salts. A flash photolysis study for the adduct involving 4′,7-dihydroxyflavylium

The adducts formed between caffeine and three hydroxyflavylium salts (4-methyl-7-hydroxyflavylium, 4′-hydroxyflavylium, and 4′,7-dihydroxyflavylium) are described and the last studied by flash photolysis. A consistent evidence of the caffeine effect on the rate constants of this system is given for the first time. A net hyperchromic effect was only observed for the adduct involving 4′-hydroxyflavylium. The results confirm previous observations that co-pigmentation is essentially a phenomenon that changes the molar fraction distribution of the several species in equilibrium, and not a result of the formation of highly colored charge transfer bands. A simple mathematical model is used to account for the experimental results.