Quantitation of pharmaceutically important phenothiazines by oxidimetry

A new spectrophotometric method for the assay of phenothiazines in pure form as well as in pharmaceutical formulations with the chromium(VI)-metol-sulfanilic acid system has been developed. The method is based on the oxidation of the drugs by a known excess of chromium(VI) and subsequent determination of the unreacted oxidant by interacting with metol and sulfanilic acid. The reacted oxidant corresponds to the drug content. The coloured species exhibits maximum absorbance at 530 nm. Beer's law is obeyed over the concentration range 5-60 micrograms ml-1 and the relative standard deviation is found to be less than 2%. The apparent molar absorptivities are in the range 3.77 x 10(3)-3.98 x 10(3) l mol-1 cm-1, the detection limits being in the range 0.6133-1.1349 micrograms ml-1. The method was successfully applied to the determination of the studied drugs in their formulations and the mean percentage recoveries were found to be 97.32-102.80%.     

Simple spectrophotometric determination of acyclovir in bulk drug and formulations

A simple and cost effective spectrophotometric method is described for the determination of acyclovir in bulk drug and in formulations. The method is based on the formation of blue coloured chromogen when the drug reacts with Folin-Ciocalteu (F-C) reagent in alkaline medium. The coloured species has an absorption maximum at 760 nm and obeys Beer's law in the concentration range 50-450 microg ml(-1). The absorbance was found to increase linearly with increasing concentration of acyclovir, which is corroborated by the calculated correlation coefficient value of 0.9998 (n = 9). The apparent molar absorptivity and Sandell sensitivity were 1.65 x 10(2) l mol(-1) cm(-1) and 1.36 microg cm(-2), respectively. The slope and intercept of the equation of the regression line are 6.87 x 10(-4) and 8.33 x 10(-3), respectively. The limit of detection was 5.68 microg ml(-1) and the limit of quantification was 18.95 microg ml(-1). The proposed method was successfully applied to the determination of acyclovir in pharmaceutical formulations. The reliability of the assay method was established by parallel determination by standard-addition method, and by recovery studies. The results demonstrated and the procedure is at least as accurate, precise and reproducible (RSD < 2%) as the official method, while being simple and less time consuming. A statistical analysis indicated that there was no significant difference between the results obtained by the proposed procedure and those of the official method.     

Spectrophotometric methods for the rapid determination of menadione and menadione sodium bisulphite and their application in pharmaceutical preparations

Two simple, rapid and sensitive spectrophotometric determination of menadione and its sodium bisulphite derivative (MSB) have been carried out. The first method involves the reaction of menadione and its sodium bisulphite derivative with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) is sodium hydroxide medium to give blue coloured product having maximum absorption at 625 nm and the coloured species is stable for more than 1 h. The Beer's law is obeyed in the range 0.4-16 microg ml(-1). The second method proposes the reaction of menadione and its sodium bisulphite derivative with resorcinol in concentrated sulphuric acid medium to give red coloured product having maximum absorption at 520 nm and is stable for 3 h. The Beer's law was obeyed in the range of 1-24 microg ml(-1). Molar absorptivity for the above two methods were found to be 7.6 x 10(3) and 4.5 x 10(3) l mol(-1) cm(-1), respectively. All the measurements were carried out at room temperature. These two methods have been successfully applied for menadione and its sodium bisulphite derivatives in injections and tablets of pharmaceutical formulations. The results compare favourably with official method.     

Application of ninhydrin to spectrophotometric determination of famotidine in drug formulations

A simple and fast spectrophotometric procedure has been developed for the determination of famotidine. The method is based on the interaction of ninhydrin with primary amines present in the famotidine. This reaction produces a blue coloured product which absorbed maximally at 590 nm. The effects of variables such as reagent concentration and reaction time were investigated to optimize the procedure. Beer's law was obeyed in the concentration range of 5-30 microg ml(-1) with molar absorptivity of 6.99 x 10(3) l M(-1) cm(-1). The results were validated statistically. The proposed method has been applied to the determination of famotidine in tablets with satisfactory results.     

Study on the charge-transfer reaction between 7,7,8,8-tetracyanoquinodimethane and drugs

The charge-transfer (CT) reaction between 7,7,8,8-tetracyanoquinodimethane (TCNQ) as a pi-electron acceptor and cinnarizine, analgin, norfloxacin as electron donors have been studied by spectrophotometric method. The charge transfer complexes between TCNQ and these drugs have stable blue color, therefore a simple, rapid, accurate and sensitive method for determination of these drugs has been developed. The optimization of the experimental conditions is described. Beer's law is obeyed in the ranges 2-18, 2-18 and 4-32 microg/ml for cinnarizine, analgin and norfloxacin, respectively. The apparent molar absorptivity of CT complexes at 743 nm is 1.58x10(4), 1.71x10(4) and 8.91x10(3) l/mol per cm, respectively. The composition of all these CT complexes are found to be 1:1 by different methods. The relative SDs are less than 3% (n = 10). The proposed method has been applied to the determination of these drugs in their each pharmaceutical dosage forms with satisfactory results.     

AAS and spectrophotometric determination of propranolol HCl and metoprolol tartrate

Two simple and accurate spectrophotometric methods are described for the determination of propranolol hydrochloride (I) and metoprolol tartrate (II). The methods are based on the reaction of each drug as a secondary amine: (a) with carbon disulphide, the formed complex extracted into iso-butyl methyl ketone (IBMK) after chelation with Cu(II) ions at pH 7.5, followed by measuring the absorbance at 435.4 nm or indirectly for the drug by flame atomic absorption spectrophotometry (AAS). The calibration graph is linear up to 40 and 60 microg ml(-1) with apparent molar absorptivities of 6.89 x 10(3) and 1.08 x 104 l mol(-1) cm(-1) and correlation coefficients of 0.9994 and 0.9995 for propranolol and metoprolol, respectively; (b) with pi-acceptors, tetracyanoethylene (TCNE), or chloranilic acid (CLA) to give highly coloured complex species. The coloured products are quantitated spectrophotometrically at 415 or 510 nm for the two drugs with TCNE and CLA, respectively, and obey Beer's Law with RSD less than 2.0. The methods were applied to the determination of these drugs in pharmaceutical preparation without interferences.     

Spectrophotometric determination of peptic ulcer sulfur-containing drugs in bulk form and in tablets

Two spectrophotometric procedures are suggested for the determination of three irreversible proton pump inhibitors, rabeprazole (RAB), omeprazole (OMP) and pantoprazole (PAN) in pure form and in different pharmaceutical formulations. The first method is based on the oxidation of RAB and PAN with potassium iodate in an acidic medium followed by extracting the liberated iodine with cyclohexane and measurement at λ = 520 nm. Beer's law is valid in the concentration ranges from 10-400 and 5-400 μg ml(-1) for RAB and PAN, respectively. The apparent molar absorptivities of the resulting coloured product were found to be 1.34 × 10(3) and 1.64 × 10(3) l.mol(-1). cm(-1) for RAB and PAN, respectively. The second method is based on the interaction of the basic drugs, OMP, RAB and PAN, in 1,2-dichloroethane with bromophenol blue (BPB), bromocresol green (BCG) and bromocresol purple (BCP) in the same solvent to produce stable coloured ion pairs with maximum absorbance at 385-405 nm. Regression analysis of Beer's plots showed good correlation in the concentration ranges 10-60, 10-60 and 5-40 μg ml(-1) for OMP, 10-150, 10-150 and 10-60 μg ml(-1) for RAB and 10-250, 10-150 and 10-100 μg ml(-1) for PAN with BPB, BCG and BCP reagents, respectively. The limits of detection are 0.46-7.69 μg ml(-1) and limits of quantitation range between 1.52-8.53 μg ml(-1). The optimum assay conditions were investigated and the recovery of the drugs from their dosage forms ranged from 99.33% to 100.5%. Intraday relative standard deviations (RSD) were 0.029-1.397% and the correlation coefficients ranged from 0.9992 to 1. The two methods can be applied successfully for the determination of these drugs in tablets. The results of analysis were validated statistically through recovery studies.     

Identification of mebeverine acid as the main circulating metabolite of mebeverine in man

Dipicrylamine and picric acid have been tested as reagents for the determination of promethazine and perphenazine. They react in neutral media with these drugs forming the coloured compounds. The compounds are sparingly soluble in water and quantitatively extracted into organic solvents. The extracts are intensely coloured and very stable. These properties have been exploited for the extractive spectrophotometric determination of promethazine and perphenazine in pure solutions and pharmaceuticals. Linear calibration graphs were obtained in the concentration range 4-40, 3-30 microg ml(-1) of promethazine and 4-80, 8-60 microg ml(-1) of perphenazine for picric acid and dipicrylamine, respectively. The relative standard deviation (RSD) is less than 0.8%.     

Spectrophotometric determination of diloxanide furoate in its dosage forms.

A simple and sensitive spectrophotometric method has been developed for the determination of diloxanide furoate in its dosage forms. The method is based on the reaction of the drug with potassium permanganate in the presence of sodium hydroxide to produce a bluish green coloured species measurable at 610 nm. The absorbance-concentration plot is linear over the range 2.5-20 microg/ml with correlation coefficient (n = 8) of 0.9998 and minimum detectability of 0.2 microg/ml (6.1 x 10(-7) M). The molar absorptivity was 1.1 x 10(4) l/mol cm. The different experimental parameters affecting the development and stability of the colour were carefully studied and optimised. The proposed method was applied successfully for the determination of diloxanide furoate in its tablet form. The results obtained were in good agreement with those obtained using the official method. The proposed method could be applied to the determination of diloxanide furoate in presence of some co-formulated drugs. The effect of sensitisers and surfactants on the performance of the proposed method was also studied. A proposal of the reaction pathway was presented.     

A sensitive spectrophotometric determination of acetaminophen.

A sensitive, accurate and precise spectrophotometric method is described for the determination of Acetaminophen (paracetamol, ACTP) in pure form and in pharmaceutical formulations. The principle of the method is the reduction, of Fe(III) to Fe(II) by the ACTP in the presence of o-Phenanthroline (o-Phen), when the orange-red coloured chelate complex [Fe(II)-(o-Phen)3]2+ the ferroin complex was formed, and its absorbance was measured at lambda = 510 nm. The apparent molar absorptivity, referred to ACTP was 3.16 x 10(4) 1 mol-1 cm-1 and the Sandell's sensitivity was calculated as 4.8 ng cm-2. The calibration graph was rectilinear over the range 0.25-10.0 ppm of ACTP and the regression equation was calculated as A = 2.06 x 10(-1) C + 4.78 x 10(-3) with a correlation coefficient of 0.9999 (n = 8). A statistical analysis by means of the Student's t-test as well as by the variance ratio F-test, indicates that the proposed new method is equivalent to the corresponding B. P. 1988 and U. S. P. XXII official methods with regard to accuracy and precision.     

Voltammetric behavior of cefixime and cefpodoxime proxetil and determination in pharmaceutical formulations and urine

Electrochemical reduction behavior of cephalosporins, Cefixime (CF) and Cefpodoxime Proxetil (CP) have been studied by using different voltammetric techniques in Britton-Robinson buffer system. Two well defined cathodic waves are observed for both the compounds in the entire pH range. Number of electrons transferred in the reduction process was calculated and the reduction mechanism is proposed. The results indicate that the process of both the compounds is irreversible and diffusion-controlled. The peak currents for CF and CP are found to be linear over the range of concentration 6.0 x 10(-8) to 1.2 x 10(-5) mol l(-1) and 8.8 x 10(-8) to 1.1 x 10(-5) mol l(-1), respectively. The lower detection limits are found to be 4.6 x 10(-8) and 8.52 x 10(-8) mol l(-1) for the two compounds. A differential pulse voltammetric method has been developed for the determination of these drugs in pharmaceutical formulations and urine samples.     

Spectrophotometric method for the determination of amlodipine besylate with ninhydrin in drug formulations.

A spectrophotometric method has been developed for the determination of amlodipine besylate in pure form and in pharmaceutical preparations. The method is based on the reaction of the primary amino group of the drug with ninhydrin in N,N'-dimethylformamide (DMF) medium producing a coloured complex which absorbs maximally at 595 nm. Beer's law is obeyed in the concentration range of 10-60 microg ml(-1) with RSD of 0.66% and molar absorptivity of 6.52 x 10(3) l mol(-1) cm(-1). All variables were studied in order to optimize the reaction conditions. The proposed method has been applied successfully to the analysis of the bulk drug and its dosage forms. No interference was observed from common pharmaceutical adjuvants. Statistical comparison of the results with the reference method shows excellent agreement and indicates no significant difference in accuracy and precision.     

A spectrophotometric method for the determination of metoclopramide HCl and dapsone

A rapid, sensitive and selective spectrophotometric method has been developed for the quantitative determination of metoclopramide hydrochloride (MCP) and dapsone (DAP) in both pure and dosage forms. The method is based on the diazo coupling reaction of the drugs with a new coupling agent, dibenzoyl methane in an alkaline medium. The resulting coloured azo dyes exhibit maximum absorption at 440 nm for MCP and at 470 nm for DAP with a molar absorptivity of 2.85x10(4) and 1.71x10(4) l mol(-1) cm(-1) for MCP and DAP, respectively. All variables have been optimized. No interferences were observed from excipients and the validity of the method was tested against reference method.     

Extractive spectrophotometric methods for the determination of nifedipine in pharmaceutical formulations using bromocresol green, bromophenol blue, bromothymol blue and eriochrome black T

Four simple, sensitive and accurate spectrophotometric methods have been developed for the determination of nifedipine in pharmaceutical formulations. These methods are based on the formation of ion-pair complexes of amino derivative of the nifedipine with bromocresol green (BCG), bromophenol blue (BPB), bromothymol blue (BTB) and eriochrome black T (EBT) in acidic medium. The coloured products are extracted with chloroform and measured spectrophotometrically at 415 nm (BCG, BPB and BTB) and 520 nm (EBT). Beer's law was obeyed in the concentration range of 5.0-32.5, 4.0-37.5, 6.5-33.0 and 4.5-22.5 microg ml(-1) with molar absorptivity of 6.41 x 10(3), 4.85 x 10(3), 5.26 x 10(3) and 7.69 x 10(3) l mol(-1) cm(-1) and relative standard deviation of 0.82%, 0.72%, 0.66% and 0.68% for BCG, BPB, BTB and EBT methods, respectively. These methods have been successfully applied for the assay of drug in pharmaceutical formulations. No interference was observed from common pharmaceutical adjuvants. Statistical comparison of the results with the reference method shows excellent agreement and indicates no significant difference in accuracy and precision.     

A selective and sensitive kinetic method for the determination of procaine and benzocaine in pharmaceuticals.

A simple stopped-flow method for the determination of procaine and benzocaine which is suitable for their routine analysis in pharmaceutical samples is reported. The method is based on a condensation reaction between each compound and 4-dimethylaminocinnamaldehyde, which yields coloured compounds and which are monitored spectrophotometrically. The calibration graph generated is linear over the range 0.5-20 micrograms ml-1 (RSD 0.73%) for procaine and 0.5-15 micrograms ml-1 (RSD 0.40%) for benzocaine, and the selectivity is very high in both cases. The proposed methods were satisfactorily applied to the determination of the two drugs in various pharmaceutical samples. A procedure for resolution of procaine-benzocaine mixtures in mass ratios between 15:1 and 1:7 with a precision of ca 1% was developed in order to determine one compound in the presence of the other with no interference.     

PVC membrane ion-selective electrodes for the determination of Hyoscyamine in pure solution and in pharmaceutical preparations under batch and flow modes

New PVC membrane electrodes selective for the determination of hyoscyamine ion (Hy(+)) based on hyoscyamine tetraphenylborate (Hy-TPB) or hyoscyamine phosphotungstate (Hy-PT) ion-exchangers as electroactive materials are described. The electrodes show a linear response for Hy(+) over the concentration range of 1.00 x 10(-5) to 1.26 x 10(-2) mol L(-1) and 1.00 x 10(-4) to 1.00 x 10(-2) mol L(-1) in case of Hy-TPB electrode applying batch and flow injection analysis (FIA), respectively, and 1.00 x 10(-5) to 4.52 x 10(-3) mol L(-1) and 6.31 x 10(-5) to 1.00 x 10(-2) mol L(-1) in case of Hy-PT electrode for batch and FIA, respectively. The lower detection limits are 3.90 x 10(-6) and 4.51 x 10(-6) at 25 degrees C for Hy-TPB and Hy-PT electrodes, respectively. The electrodes posses near Nernstian slopes of 56.5 and 57.8 mV/decade for Hy-TPB and Hy-PT electrodes, respectively, and a fast potential response of < or =20 s which is almost constant over a pH range of 3-10. Selectivity coefficient data for some common inorganic cations, sugars, amino acids and the components, other than hyoscyamine, of the mixed drugs investigated show negligible interference. The electrodes have been applied to the potentiometric determination of hyoscyamine in pure solution and in pharmaceutical preparations under batch and FIA conditions and as end point indicator electrode for the determination of hyoscyanine using potentiometric titration. For the concentrations (1.08 x 10(-5) mol L(-1) to 3.16 x 10(-3) mol L(-1)) an average recovery of 99.95% with relative standard deviation of 0.63% has been achieved. The effect of temperature on the electrodes was also studied.     

LC of pharmaceutically important halogenated 8-hydroxyquinolines after precolumn derivatization with Pd (II)

An accurate, sensitive, and selective reversed phase high performance liquid chromatographic (HPLC) method was developed for the analysis of two halogenated 8-hydroxyquinoline derivatives; clioquinol (CQN) and iodoquinol (IQN). The proposed method depends on the complexation ability of the studied compounds with Pd(II) ions. Reversed phase chromatography was conducted using a 300 x 3.9 mm i.d. stainless steel column packed with 10 microm Bondclone phenyl at ambient temperature. A solution containing 0.005% w/v of Pd(II)-chloride in a mixture of acetonitrile-methanol-water (3:3:4 v/v/v) of pH 3.7 as a mobile phase pumped at a flow rate of 0.75 ml min(-1). UV-detection was performed at 282 and 285 nm for CQN and IQN, respectively. The method showed excellent linearity in the range 0.05-1.8 and 0.1-3.0 microg ml(-1) with limit of detection (S/N=2) 4.8 ng ml(-1) (1.57 x 10(-8) M) and 6.4 ng ml(-1) (1.61 x 10(-8) M) for CQN and IQN, respectively. The suggested method was successfully applied for the analysis of the studied drugs in bulk with average% recoveries of 99.68+/-0.44 for CQN and 99.65+/-0.53 for IQN. The proposed method was successfully applied for the analysis of the studied drugs in single or combined dosage forms with average% recoveries of 99.41+/-0.51-100.02+/-0.63. The proposed method could be used successfully for the determination of the studied compounds in the presence of their degradation product as they could be eluted with different retention times. The presence of metronidazole (MNZ) or tolnaftate (TFT) with the studied drugs does not affect their accurate determination. The results obtained were favorably compared with those obtained by the reference method. The results were satisfactorily, accurate, and precise.     

Determination of glutathione in hemolysed erythrocyte by flow injection analysis with chemiluminescence detection

In this work, a new sensitive method is introduced for analysis of glutathione at trace levels in blood samples. The method is based on the effect of glutathione on the chemiluminescence signal of the oxidation of luminol by sodium periodate in basic solution. The influence of chemical and manifold variables on the sensitivity was studied. At the optimized conditions, the linear range for the determination of glutathione was 1.0x10(-8) to 1.0x10(-5)molL(-1) with the detection limit (3sigma) of 8x10(-9)molL(-1). The relative standard deviation for 10 repeated measurements of 1.0x10(-6)molL(-1) of glutathione was 4%. The results of the method were compared with the Ellman reference method and no significant difference was found. The influence of potential interference substances on the determination of glutathione was studied. The proposed method was applied successfully for the determination of glutathione in real samples such as erythrocyte hemolysed in normal subjects and diabetes.     

Application of pi-acceptors to the spectrophotometric determination of lisinopril in commercial dosage forms

Two simple, rapid and sensitive spectrophotometric methods have been proposed for the determination of lisinopril in pure form and pharmaceutical formulations. The methods are based on the charge transfer complexation reaction of the drug with 7,7,8,8,tetracyanoquinodimethane (TCNQ) and p-chloranilic acid (pCA) in polar media. The lisinopril-TCNQ and lisinopril-pCA charge transfer complexes dissociate in acetone and methanol, respectively, and yield coloured TCNQ and pCA radical anions which are measured spectrophotometrically at 743 and 525 nm. Under optimised experimental conditions, Beer's law is obeyed in the concentration range of 2-26 and 25-300 microg ml-1 with molar absorptivity of 1.432x10(4) and 1.192x10(4) l mol-1 cm-1 for TCNQ and pCA methods, respectively. Both the methods have been applied to the determination of lisinopril in pharmaceutical dosage forms. Results of analysis are validated statistically.     

Determination of some aminobenzoic acid derivatives: glafenine and metoclopramide

Simple, sensitive and accurate spectrophotometric methods for the determination of glafenine and metoclopramide hydrochloride are described. The first method is based on the oxidation of glafenine with iodic acid in strong acid medium to give a coloured diphenylbenzidine derivative and subsequent measurement of the coloured product at 509 nm. Beer's law is obeyed over the concentration range 2.5–20 μg ml⁻¹. The second method depends on the interaction of metoclopramide hydrochloride with p-dimethylaminocinnamaldehyde, to give a red coloured schiff's base with an absorbance maximum at 548 nm. Obedience to Beer's law is achieved over the concentration range 5–30 μg ml⁻¹. First-derivative method is used to overcome the slight interference of p-dimethylaminocinnamaldehyde reagent blank at the wavelength of measurement. Linearity between the peak heights at 576 nm versus concentration range 5–25 μg ml⁻¹ metoclopromide hydrochloride is obtained. The proposed methods have been successfully applied to the determination of these drugs in commercial products without interference. The validity of the methods is assessed by applying the standard addition technique, the relative standard deviation is less than 1%. The proposed methods are compared with reference methods with good agreement.