Spectrophotometric Determination of Chlorpromazine Hydrochloride in Pharmaceutical Preparations by Oxidative Coupling reaction

An easy and simple spectrophotometric method was described for estimating chlorpromazine Hydrochloride drug in aqueous solution. Where The method was adopted on oxidative coupling reaction of the drug with pnitro aniline in the presence of ceric(IV) ammonium nitrate and hydrochloric acid solution an orange-brown product dye was obtainded with maximum absorption at 525 nm. with moler absorptivity of 9.24×10 l. mol. cm -1 and sandell's sensitivity of 0.0385 μg.cm Beer's law is obeyed over the concentration range of (12-46) μg.ml -1 . The method was applied successfully for the estimating the drug it's on pure condition or in pharmaceutical preparations (Largactil drug).


Introduction
Phenothiazine is a very important class of organic compound with strong biological efficacy used as a treatment for severe and moderate psychosocial conditions [1,2] .It binds with certain receptors of dopamine D2 and affects its function and thus affects many processes in the body such as metabolism [3] and is used for epilepsy [4], stomach, liver and bowel diseases [5] and tetanus treatment [6]. Many phenothiazine derivatives is formally found in the British pharmacopoeia [7] and the Indian pharmacopoeia [8]. Chlorpromazine is one of the most important phenothiazine and the scientific name of chlorpromazine according to the IUPAC system is: 2-chloro-10- [3-(dimethylamino)propyl] phenothiazine monohydrochloride. Several spectral methods have been used to estimate chlorpromazine hydrochloride, which is generally based on the oxidation and reduction reaction [9]

Result and Discussion
Optimal conditions were studied, which affect the resulting absorption, intensity composed and on color contrast to get the best condition 2 ml of chlorpromazine solution with a concentration of 300µg/ml was used in final volume 25 ml.

[Effect of the amount of oxidizing agent]
The effect of adding different amount of the oxidizing agent on the absorption intensity was studied. A series of volume (0.1-3) ml of oxidizing agent ceric (IV) ammonium nitrate 0.01 Molar concentration was taken with 1ml reagent p-nitro aniline and 1ml of hydrochloric acid solution. It was found that the best amount (0.5) ml was given the absorption intensity, and this volume was selected in all subsequent measurements.

[Effect of the Amount of coupling Reagent]
The effect of reagent quantity p-nitro aniline was studied on the absorption intensity. A series of volume of reagent (0.5-3) ml 0.01 Molar were taken using 0.5 ml of oxidizing reagent and 0.5 ml hydrochloric acid solution. The addition of 1 ml of reagent was found to be the best to give it the highest absorption intensity and this volume was selected in all subsequent measurements.

[Effect of the Amount of acid]
Some of weak and strong acids have been used and found (1) ml of hydrochloric acid give the maximum absorption intensity and this volume was elected in all following measurements.

[Effect of Order of Addition]
It was found that the best addition sequence that gives the highest absorption intensity is

[Stability of reaction product]
It was found that the value of absorption of the color product remained stable for a period of not less than 70 minutes and this time is suitable for completion of many measurements and results show in Table 2 Table 2: Stability of reaction product.

[Solvent effect]
After all components of the reaction were added according to the method used, different solvent were used to complete the volume to the extent of the mark in 25 ml volumetric flask to obtain the highest absorption, and the figure indicates that water is a good medium for the reaction and gives the highest absorption at wavelength 525 nm.  The final absorption spectra were measured after optimum conditions were established Table 3.

[Precision and Accuracy]
The precision and accuracy for calibration curve it has been measured by determination three different concentration of 300 µg/ml chlorpromazine hydrochloride and the product were show in Table 4 which indicate good thoroughness and agreement.

[Stoichiometry of chlorpromazine hydrochloride-p-nitro aniline complex]
The stoichiometry of the reactant was investigated by Job method[19] the result obtain indicated that the existence of 1:1 chlorpromazine-p nitro aniline at 525nm .

Statistical evaluation of the results of the proposed method
To determine the success of the suggest method for the determination of chlorpromazine in pharmaceuticals, the validity of application of the method was examined by testing f and t for the accuracy and precision of the proposed method and the results are shown in Table 6. The results of the above table show that the calculated F and t values of the two formulas (Tablet, injections) is less than the value of the tabular F and t at 95% confidence limit and for four degrees of freedom. This indicates the accuracy of the spectral method used.

Comparsion of method
Some of the physical variables of the proposed method were compared with the differences in the spectral methods from the literature used in the estimation of chlorpromazine. We conclude from the results shown in Table 7 that the proposed method has a wide range of estimation and has been successfully applied in estimating the compound under study in two pharmaceutical preparations , As well as good sensitivity in compared to other methods

Conclusions
An easy and simple spectrophotometric method was described for estimating chlorpromazine Hydrochloride drug in aqueous solution. Where The method was adopted on oxidative coupling reaction of the drug with p-nitro aniline in the presence of ceric(IV) ammonium nitrate and hydrochloric acid solution an orange-brown product dye was obtainded with maximum absorption at 525 nm. with moler absorptivity of 9.24x10 3 l. mol -1 .
Cm -1 and sandell's sensitivity of 0.0385 µg.cm -2 Beer's law is obeyed over the concentration range of (12-46) µg.ml -1 . The method was applied successfully for the estimating the drug it's on pure condition or in pharmaceutical preparations (Largactil drug).