Spectrophotometric Determination of Dimethindene in Pharmecutical Preparations and Water Samples

A simple, accurate, rapid and sensitive visible spectrophotometric method has been developed for the determination of dimethindene in pure and pharmaceutical preparations. The method is based on the reaction of dimethindene with potassium permanganate in alkaline solution to form a bluish green coloured chromogen with an absorption maximum at 610 nm. Beer’s Law was obyed in the range of 0.2-2.8 μg/ml with molar absorbitivity of 4×10 3 L.mol. -1 .cm -1 . The optimum conditions for all colour development are described and the propsed method has been successfully applied for the determination of dimethindene in pharmaceutical preparations and water samples. The common excipients and additives did not interfere in the proposed method.


INTRODUCTION
Dimethindene:N,N-dimethyl-2-[3-(RS)-1-(pyridine-2-yl)ethyl]-1hinden-2-yl]ethanamine.With a molecular formula of C 22 H 24 N 2 and molecular weight of (292.8).Its structural formula is as follows It is antihisatamine agent and may be considered as a derivative of the unstandard propylamines [1,2], the antihistamine avtivity resides mainly in the levo-rotory isomer.It is mildly sedative and is reported to have mast-cell stabilizing properties.It is used for the symptomatic relief of allergic conditions including urticaria and angioedema and rhinitis and in pruritic skin disorders.It is also used in compound preparations for the symptomatic treatment of coughs and the common cold [3,4].The literature revealed that dimethindene has been determined by mean of a few analytical methods.These include HPLC [5-7], capillary electrophoresis [8].The spectrophotometric methods using different reagents like 7,7,8,8-tetracyanoquinodimethane (TCNQ) [9], p-chloranilic acid [10], and fast green FCF [11] have also been reported for its determination.These methods suffer from some drawbacks like large number of solvent for the extraction, instability of colour, use of toxic reagents etc. in the present work, a simple sensitive spectrophotometric method for the determination of dimethindene in water samples and in pharmaceutical preparations.The method based on the oxidation of dimethindene by a potassium permanganate to form a bluish green coloured chromogen with an maximum absorption at 610nm.

EXPERIMENTAL 2.1 Apparatus
Optima sp-3000 plus UV-visible spectrophotometer with 1.0cm quartz cells was used for all absorption measurements.

Reagents
All chemicals used were of analytical reagent grade and all solution were prepared in distilled water.A standard solution of dimethindene (100 ppm) was prepared by dissolving 0.1g of pure drug in 1L distilled water.It was later diluted with water to get concentration of 10 ppm.Potassium permanganate 0.02M.This solution was prepared by dissolving 3.2g in 1L distilled water, Then the solution was heated to boling and then filtered CH N CH 2 CH 2 N(CH 3 ) 2 CH 3 through asbestose.The filtered solution should be kept in the dark and standardized immediately before use.[12].Sodium hydroxide (10N).This solution was prepared by dissolving 40 g of pure NaOH in 100 ml distilled water.

RECOMMENDED PROCEDURE
Different a liquots of standard dimethindene solution equivalent to 5-70µg were transferred into a series of 25ml volumetric flask, 7 ml of 10N NaOH and 4 ml of 0.02M KMnO 4 were added.The content was mixed and let stand for 5 min with occasional shaking.The volume was diluted to the mark with distilled water and mixed well.The absorbance of each solution was measured at 610nm against a reagent blank.

Procedures for pharmaceutical preparations: 3.1.1 Oral drops and syrup:
The content of 5 bottles were mixed well in 1L dried beaker.An a liquots equivalent to 10 mg of dimethindene was transferred into 1L volumetric flask and diluted with distilled water to the volume.The determination of dimethindene proceeded as desired under the recommended procedure.

Capsules:
The content of 10 capsules were mixed thoroughly, an accurate weight equivalent to 10mg of dimethindene was transferred in to 100 ml beaker added 50 ml of water and mixed well for 30 mint filtered, transferred quantitatively to 1L volumetric flask and completed to the volume.The determination of dimethindene proceeded as described under recommended procedure.

Procedure for water samples
Distilled and tap water samples (100ml) were fortified with 1 mg of dimethindene.the fortified water samples were analyzed as desired under recommended procedure .

RESULTS AND DISCUSSION
The reaction between dimethindene and KMnO 4 in alkaline medium yields a green colour dye due to the formation of manganate ions, which absorb at 610nm fig( 1).The various experimental parameters affecting the development and stability of the reaction product was optimized by changing each variable in turn while keeping all other variables constant.

Effect of KMnO 4 concentration
The absorbance increase with increasing KMnO 4 concentration.It was found that 4 ml of 0.02M KMnO 4 was adequate for the maximum absorbance for the dye formed

Effect of NaOH
Trials were made to determine the drug through oxidation with KMnO 4 in neutral, acidic and alkaline media,but very little oxidation of dimethindene was observed in neutral and acidic solution.It was found that increasing the volume of 10M NaOH would increase absorbance of the reaction product up to 7 ml.after that NaOH has no effect on the absorbance as shown in fig ( 2

Effect of temperature
The resulting product of the proposed method were studied at room temperature (25±5 C 0 ), Higher temperature causes turbid colour, therefore, room temperature was selected as suitable temperature.

Effect of reaction time
The colour formed immediately after addition of potassium permanganate and became stable after 5 minutes, therefor 5minutes as a development time was selected as a suitable time in the recommended procedure, the colour obtained was stable for at least 3 hours.

Effect of order of addition
To test the effect of order of the addition of the reagents on the absorbance of the product, different order were tested.The selected order was sample solution, NaOH followed by KMnO 4 solution which was gave high absorbance value.

Calibration graph
Employing the conditions described in the recommended procedure a linear calibration graph of dimethindene is obtained fig( 3), which shows that Beer's law is obeyed over the concentration range 0.2-2.8µg/ml with correlation coefticient of 0.9998, intercept of 0.027 and slope of 0.036 The limit of detection was evaluated as [13].
where (b) is the slope and (so) is the standard deviation of the regression line.The limit of detection was 0.016 µg/ml.The conditional molar absorptivity of the product formed was found to be 4×10 3 L. mol -1 .cm -

ACCURACY AND PRECESION OF THE PROPOSED METHOD
To evaluate the accuracy and precesion of the method, a pure drug solution was analyzed at three different concentrations, each determination being repeated six times the relative error (%) and relative standard deviation (%) values are summarized in table (1).From table (1), it is clear that the relative error of less than 1.8% and the method is found to be precise with RSD value less than 2.1%.for a better picture of reproducibility, aseries of experiments were performed in which the standard drug solution was determined at three different levels each day for six days, with all solutions being prepared a fresh each day.The day-to-day relative standard deviation values were in the range of 0.9-2.0 % and represent the best appraisal of repeatability of the proposed methods.

INTERFERENCE STUDIES
In order to asses the possible of the proposed method, the effect of substance that often accompany with dimethindene in various pharmaceutical products were studied by adding different amount of substances to 40µg of dimethindene.An attractive feature of the method is its relative freedom from inference by the usual diluents and expcipients in amount for in excess of their normal occurance in pharmaceutical preparations.The results are given in table (2).

STOICHEIOMETRY OF THE REACTION:
The stoicheiometry of the reaction between dimethindene and KMnO 4 was investigated using job's and mole ratio methods, the result obtained show that 1:2 drug to KMnO 4 and the suggested reaction and structure of the product might be written as [14][15][16]

ANALYTICAL APPLICATION
The proposed method was satisfactorly applied to the determination of dimethindene in its pharmaceutical formulations and water samples .the results of the assay of the pharmaceutical formulations revels that there is close agreement between the results obtained by the proposed method and the lable claim.The results were also compared statistically by student t-test and by the variance ratio F-test with those obtained by spectrophotometric literature method [17] at 95% confidence level.The calculated t-and Fvalues did not exceed the theoretical values indicating that there was no significant differences between the precision of the proposed and literature method as cited in table (3) , And the results of water samples table (4) show that the recovery values obtained were close to 100%.

CONCLUSION
The proposed method was simple, accurate, precise, sensitive and low economical cost.Furthermore, the proposed method doesn't require elaboration of procedures, which are usually associated with chromatographic methods.The proposed method could be applied successfully for determination of dimethindene in pure form as well as in different dosage forms.

2)
Wilson and Glsvold's, "Text-book of organic Medical and pharmaceutical chemistry, 10

Table ( 1): Accuracy and precision of the method Dimethindene taken
a: Mean of six determinations

Table ( 2): Determination of 40µg of dimethindene in the presense of excipients and other substances. Interfering substances Amount added / µg Amount of dimethindene found * RSD %
* average of six determinations